2015 The British Society for Rheumatology and British Health Professionals in Rheumatology Annual Meeting 2015

28 April – 30 April 2015 Manchester Central, Manchester, UK The abstracts are freely available online to all visitors to the Rheumatology website (http://www.rheumatology.oxfordjournals.org). RheumatologyDOI is incorrect10.1093/rheumatology/ker000ker000ContentsRheumatologyContents- Contents2012000000002012Volume 51 Supplement 3 May 2012 Volume 54 Supplement 1 April 2015

CONTENTS

Rheumatology 2015 Abstracts

INVITED SPEAKER ABSTRACTS (TUESDAY 28 APRIL 2015) I01–I03 Imaging in rheumatology: a practical perspective i1 I04–I06 Biologics in SLE: getting close to lift off (at last!) i1 I07–I09 Shared decision making and self-management support: why they matter in i1 rheumatology I10–I11 Challenges of remote and rural rheumatology i2 I12–I15 A step in the right direction: addressing foot health in rheumatoid arthritis i2 I16–I18 Musculoskeletal health and vocational rehabilitation i3 I19–I21 Making it happen: optimizing the service to RA patients i4 I22–I24 Community-based physical activity for osteoarthritis: the emerging role of i4 non-healthcare professionals I25–I26 Post-doctoral, PhD and postgraduate student network i5 I27–I32 Jewels in the Crown and top scoring abstracts (including Michael Mason and Garrod i5 prize winners and young investigator award) I33 Heberden Round i6 INVITED SPEAKER ABSTRACTS (WEDNESDAY 29 APRIL 2015) I34–I36 Pain in the 21st century: sensory–immune interactions, biologic agents and i8 bisphosphonates I37–I39 The British Society for : not the usual suspects: novel players in immune i8 homeostasis I40–I42 Essentials in rheumatology: disease assessment and management i9 I43–I45 Quality not quantity: research training in qualitative methods i9 I46–I49 Comorbidities in rheumatoid arthritis i10 I50–I54 BHPR workshop: measuring disease activity in axial spondyloarthropathy and ankylosing i10 spondylitis I55–I57 Hypermobility: a pain to manage? i11 I58–I60 The British Society for Immunology: Infection and autoimmunity: the missing links i11 I61–I63 Essentials in rheumatology: clinical knowledge and practice i12 I64–I66 Diagnosis and management of common shoulder problems in primary care i12 I67–I70 Specialized services commissioning: what’s in it for rheumatology? i13 I71–I72 BRiTs: adolescent rheumatology: what rheumatology trainees need to know i13 I73–I75 The gut microbiome and inflammatory arthritis i14 I76–I77 Essentials in rheumatology: update from the experts i14 I78–I80 Improving quality of life for older adults with musculoskeletal conditions i14 I81 Heberden Oration i15

www.rheumatology.oxfordjournals.org INVITED SPEAKER ABSTRACTS (THURSDAY 30 APRIL 2015) I82–I84 Pharmacoepidemiology: new truths, new lies i16 I85–I87 How to write, review and edit for rheumatology journals i16 I88–I90 Ageing well: is it about bone or muscle or both? i17 I91–I93 Adolescent and young adult rheumatology i18 I94–I96 How can we encourage patient participation in the clinic? i18 I97–I99 Rheumatic disease and the kidney i18 I100–I101 BRiTs: seronegative arthritides: test your knowledge! i19 I102–I104 BSR clinical guidelines i19 I105 Droitwich Medical Trust Lecture i19 I106–I108 Opportunistic infections i19 I109–I110 BRiTs: dermatological manifestations of rheumatic disease: all you i20 need to know I111–I113 The challenge of public education in rheumatology i20 I114–I116 Get fired up for audit and research i20 I117–I119 From TNF inhibition to biosimilars: managing safety and quality i21 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS (TUESDAY 28 APRIL 2015) O01–O06 RA outcomes and comorbidities and Young Investigator Prize winner i22 O07–O12 Biologics and inflammatory arthritis i25 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS (WEDNESDAY 29 APRIL 2015) O13–O18 Connective tissue diseases i30 O19–O24 Imaging i33 O25–O30 BHPR i35 O31–O36 Primary care i38 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS (THURSDAY 30 APRIL 2015) O37–O42 Basic science i41 O43–O48 Adolescent and young adult rheumatology i44 O49–O54 Genetics i47 POSTER VIEWING I (TUESDAY 28 APRIL 2015) 001–026 Case reports i50 027–044 Epidemiology i59 045–051 Primary care i66 052–055 Rheumatoid arthritis: pathogenesis i69 056–080 Rheumatoid arthritis: treatment i71 081–089 Rheumatoid arthritis: clinical features i82 090–107 Rheumatoid arthritis: comorbidities i85 108–113 Miscelleaneous rheumatic diseases i93 POSTER VIEWING II (WEDNESDAY 29 APRIL 2015) 114–140 BHPR audit and clinical evaluation and BHPR Clinical Prize winner i96 141–155 BHPR research: qualitative i105 156–164 BHPR research: quantitative i111 165–185 Health services research, economics and outcomes research i114 186–189 Muscle disorders i122 190–191 Orthopaedics and rehabilitation i123 192–194 Osteoarthritis: clinical features i124 195 Osteoarthritis: pathogenesis i125 196–201 Osteoarthritis: treatment i125 202–212 Osteoporosis and metabolic bone disease i128 213–216 Sjo¨ gren’s syndrome and other connective tissue disorders i131 217–231 Spondyloarthropathies (including psoriatic arthritis) i133 232–235 Soft tissue and regional musculoskeletal disease, fibromyalgia i139 POSTER VIEWING III (THURSDAY 30 APRIL 2015) 236 Basic science i142 237–238 Biology of bone cartilage and connective tissue i142 239–240 Cytokines and inflammation i143 241–251 Education i143 252–259 Genetics i148 260–262 Imaging i151 263–265 Metabolic and crystal arthropathies i152 266–277 Paediatric and adolescent rheumatology i153

www.rheumatology.oxfordjournals.org 278–281 Pain i158 282–288 Scleroderma and related disorders i159 289–303 Systemic lupus erythematosus and antiphospholipid syndrome i162 304–318 Vasculitis i168 E-POSTER ABSTRACTS E01–E26 Abstracts i175 E27–E28 Epidemiology i182 E29–E30 Health services research, economics and outcomes research i183 E31 Primary care i184 E32 Rheumatoid arthritis: pathogenesis i184 E33–E52 Rheumatoid arthritis: treatment i184 E53 Rheumatoid arthritis: clinical features i192 E54–E57 Rheumatoid arthritis: comorbidities i192 E59 Miscellaneous rheumatic diseases i193 E60–E65 BHPR: Audit and clinical evaluation i193 E66 BHPR Research: qualitative i195 E67 Orthopaedics and rehabilitation i196 E68 Osteoarthritis: clinical features i196 E69 Osteoarthritis: pathogenesis i196 E70–E71 Osteoarthritis: treatment i196 E72–E73 Osteoporosis and metabolic bone disease i197 E74–E77 Spondylarthropathies (including psoriatic arthritis) i198 E78–E81 Soft tissue and regional musculoskeletal disease, fibromyalgia i199 E82 Basic science i200 E83-E85 Education i201 E86 Imaging i202 E87–E88 Metabolic and crystal arthropathies i202 E89–E95 SLE and antiphospholipid syndrome i203 E96 Vasculitis i205

ABSTRACT REVIEWERS i206

AUTHOR INDEX i207

Every effort has been made to faithfully reproduce the abstracts as submitted. However, no responsibility is assumed by the organizers for any injury and/or damage to persons or property as a matter of product liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Because of rapid advances in the medical sciences, we recommend that independent verification of diagnoses and drug doses should be made.

www.rheumatology.oxfordjournals.org

i1 Tuesday 28 April 2015 INVITED SPEAKER ABSTRACTS

patients have required regular oral steroids. Another small report of non-renal lupus also confirmed the potential reduction in oral steroids IMAGING IN RHEUMATOLOGY: over the 6 months following diagnosis and an equivalent clinical benefit A PRACTICAL PERSPECTIVE compared with those given conventional steroids and immunosup- pression. Several further trials of rituximab or an equivalent fully humanized monoclonal anti-CD20 are now envisaged. As an alter- native, epratuzumab (which blocks the CD22 molecule on B cells) has I01. BACK PAIN: WHEN TO (AND NOT TO) IMAGE shown some encouraging results in a provisional trial using the BILAG- based Composite Lupus Assessment disease activity assessment Philip Helliwell1 tool. Interestingly, only some dose regimens were effective, but the 1Leeds Institute of Rheumatic and Musculoskeletal , results were sufficiently compelling to encourage the pharmaceutical University of Leeds, Leeds, UK company concerned to undertake two large international trials of epratuzumab; these results are awaited with great interest. The sense Non-invasive tomographic imaging, such as MRI and CT, has enabled of frustration around the use of B cell depletion in lupus has been better quality care for people with back pain. However, this has come palpable. The early encouraging signs allied to its successful use in at a cost, both financial and medical. On the positive side, there is other related conditions notably RA and vasculitis led to the hope that better diagnostic imaging and better targeted . On the negative B cell depletion would be generally accepted as a viable treatment side, there is overdiagnosis and sometimes overtreatment. Guidelines method. The failure of the EXPLORER and LUNAR studies threatened for the use of plain radiography in back pain have been drawn up to to call a halt to this form of treatment, but more encouraging recent avoid unnecessary radiation and inappropriate imaging. Examples will studies have again rekindled the hope this is a variable therapeutic be given to illustrate these points and the question asked: should approach. From the regulatory perspective however the jury is still out. equivalent guidelines be developed for CT and MR? Disclosure statement: The author has declared no conflicts of Disclosure statement: The author has declared no conflicts of interest. interest.

I05. BLOCKING B-CELL STIMULATING FACTORS I02. IMAGING PERIPHERAL JOINTS IN RHEUMATOLOGY: (E.G. BENLYSTA/ATACICEPT) WHAT TO USE AND WHEN Joan Merrill1 1 Philip Conaghan 1Rheumatology, Rheumatology, Oklahoma, OK, USA 1Leeds Institute of Rheumatic and Musculoskeletal, Medicine University of Leeds, Leeds, UK Abstract not provided. Disclosure statement: The author has declared no conflicts of Abstract not provided. interest. Disclosure statement: The author has declared no conflicts of interest. I06. BLOCKING INTERFERON-ALPHA AND OTHER TARGETS (E.G. ABATACEPT/LUPUZOR) I03. PET-CT IMAGING IN RHEUMATOLOGY: NEW ERA OR FALSE DAWN Edward Vital1 1 1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, Andrew Scarsbrook University of Leeds, Leeds, UK 1Radiology and , Leeds Teaching Hospitals Trust, Leeds, UK Abstract not provided. Disclosure statement: E.V. has received consultancy fees from GSK; Abstract not provided. has received honoraria from Roche and Chugai; and has received Disclosure statement: The author has declared no conflicts of grants or research support from Roche and Sandoz. interest.

BIOLOGICS IN SLE: GETTING CLOSE TO LIFT OFF (AT LAST!) SHARED DECISION MAKING AND SELF-MANAGEMENT SUPPORT: WHY THEY MATTER IN RHEUMATOLOGY I04. BLOCKING B-CELLS (ANTI-CD20/ANTI-CD20) David A. Isenberg1 1 Rheumatology, University College London, London, UK I07. WHY DO SHARED DECISION MAKING AND SUPPORT FOR SELF-MANAGEMENT MATTER IN LONG-TERM B cell depletion in SLE can appear as two steps forward, two steps CONDITIONS? backwards, one step forward, etc. Following the introduction of rituximab (combined with CYC and methylprednisolone) in 2000 for the Nick Lewis-Barned1 treatment of lupus patients who had failed conventional therapy, 20 1Royal College of , London, UK groups around the world reported great success in treating a variety of lupus features in open-label studies. This encouraged the view that Shared decision making (SDM) and support for self-management larger-scale trials of rituximab would be as successful as they proved (SDM) refer to a set of attitudes, skills systems and tools that support to be in RA and vasculitis. Sadly both the EXPLORER Trial (focusing on patients to become equal partners in the decisions and plans about non-renal lupus) and the LUNAR trial (of patients with LN) failed to their care. Around 85% of clinicians believe they involve patients in meet their end-points. Post-hoc analyses did provide some measure their care, but 50% of patients would like to be more involved than of hope indicating, for example, that a significant improvement in they are already. At the same time, evidence shows that patients who abnormal serologies were detectable. Further encouragement has are more involved in their care, especially those with long-term come from an important, albeit open-label study, demonstrating that conditions are more satisfied, make better use of treatments and after 2 years of treating 50 patients with biopsy-proven LN at the time resources to manage their condition(s) and tend to have better of diagnosis with rituximab followed by low-dose MMF, only two outcomes. We will explore the evidence for this in the session and

The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected] i2 Tuesday 28 April 2015 INVITED SPEAKER ABSTRACTS

what evidence there is for more effective strategies to deliver SDM and to make a 500-mile round trip to Aberdeen for a DXA scan. In order to SSM. address the inequities in service provision, the Grampian Osteoporosis Disclosure statement: The author has declared no conflicts of Service has developed a mobile DXA scanning service (GO-MOBILE). interest. Mobile DXA scanning units exist elsewhere in the UK with variable success; however no such service exists for island communities. This presentation discusses the development of GO-MOBILE. Firstly, I08. HOW SHARED DECISION MAKING AND SELF- current referral patterns for DXA scanning between island and urban MANAGEMENT SUPPORT HAVE BEEN USED IN PRACTICE regions will be reviewed, along with the barriers to referral for DXA Alan Nye1 scanning. Secondly, examples of mobile bone scanning services 1Pennine MSK Partnership Ltd, Oldham, UK elsewhere in the UK will be explored along with the factors determining their success or otherwise. Thirdly, the logistical challenges encoun- Abstract not provided. tered in developing the service locally will be examined. Finally, the Disclosure statement: A.N. has received research funding from the unique challenges to the provision of high quality, patient centred care Bupa Foundation. within remote and rural areas will be summarized. Disclosure statement: The author has declared no conflicts of interest. I09. SHARED DECISION MAKING AND SELF-MANAGEMENT SUPPORT FROM A PATIENT PERSPECTIVE Jacqui Pollock1 1Self Management UK, Manchester, UK

Abstract not provided. A STEP IN THE RIGHT DIRECTION: Disclosure: ADDRESSING FOOT HEALTH IN RHEUMATOID ARTHRITIS

CHALLENGES OF REMOTE AND RURAL I12. FOOT HEALTH IN RHEUMATOID ARTHRITIS: PATIENTS’ UNMET NEEDS TO BE ADDRESSED BY THE RHEUMATOLOGY RHEUMATOLOGY TEAM Savia de Souza1 1Academic Rheumatology, King’s College London, London, UK I10. THE INFLUENCE OF RURALITY ON MUSCULOSKELETAL DISEASE This presentation will begin with discussing the prevalence of foot problems in RA patients and why feet are of importance to them. It is Anthony Woolf1 known that seeing a podiatrist in the early stages of RA results in better 1Department of Rheumatology, Royal Cornwall Hospital, Truro, UK outcomes; making an early referral essential. Feet are important in reflecting RA disease activity and can often be amongst the first joints Rurality can impact on musculoskeletal diseases through differences affected. They are necessary for mobility and therefore impact in their epidemiology and in their outcome and factors which patients’ independence and quality of life. RA mainly affects women determine these. In fact, there is limited evidence of differences in who often link footwear to body image and self-confidence. Having epidemiology in rural versus urban areas. The prevalence of regional unsightly feet and being restricted in choice of footwear can affect self- musculoskeletal pain is similar, chronic widespread pain modestly esteem. Thus foot problems go beyond the functional parameters increased and OA higher in rural versus urban settings. However, often focused on by health care professionals. Patients’ views on outcomes may be influenced by differences in access to health and unmet needs which they would like addressed by their rheumatology social care and informal support as well as differences in the social team will then be presented. These views have been gathered through determinants of health. Rurality is often associated with low paid conducting two focus groups with RA patients and through reviewing manual jobs, higher unemployment and inaccessible healthcare available literature. These views will be compared with what is through a lower density of health workers, especially experts, and expected from the Standards of Care for Musculoskeletal Foot poor transportation. There are differences in thresholds for seeking Health Services document produced by the Rheumatic healthcare or for being referred to more expert care. There is often less Care Association in 2008. The view of the majority of patients from social support. Place of residence is a dimension of health and health the focus groups is that feet are not looked at or given much attention care inequalities and a component of the PROGRESS-Plus framework. by the rheumatology team. Possible reasons why this is will be A qualitative study in Cornwall, which has a scattered population with explored, having also conducted a survey of rheumatology clinicians, almost 50% living outside towns with populations over 3000, explored and why it is important that clinicians do not solely rely on patients to how RA affected the person’s ability to participate in all aspects of life. self-report foot problems. Finally, recommendations will be made on Issues identified were transport, employment, social support, access how service can be improved in rheumatology outpatient clinics to to exercise facilities and seeking information. A website with locally address these concerns. specific information has addressed some of these issues. Recognizing Disclosure statement: The author has declared no conflicts of the importance a person’s place of residence as a determinant of interest. equity of their health and healthcare is important. Disclosure statement: The author has declared no conflicts of interest. I13. HOW THE FOOT IS AFFECTED BY RHEUMATOID ARTHRITIS AND NON-SURGICAL MANAGEMENT OPTIONS I11. MOVING PATIENT CENTRED CARE CLOSER TO HOME; AVAILABLE

GO-MOBILE: A MOBILE DXA SCANNING SERVICE FOR 1 ISLAND COMMUNITIES Lynne Hazell 1Foot Health, Artesian Clinic, Guy’s and St Thomas’ Community Foot Rosemary J. Hollick1 Health, London, UK 1Institute of Applied Health Sciences, School of Medicine and , University of Aberdeen, Aberdeen, UK As foot specialists, the podiatry profession has skills to assess lower limb vascular, neurological, dermatological and musculoskeletal Measurement of BMD by DXA is routinely used to diagnose issues which underpin treatment for those with health issues such as osteoporosis, as part of individual fracture risk assessment and to RA that can lead to tissue compromise and joint . This monitor BMD over time and in response to treatment. In many rural presentation will outline the range of common affecting the communities, access to DXA scanning is limited, leading to inequities rheumatoid foot and focus on the role of the podiatrist in non-surgical in service provision compared with those living in urban areas. The management and implementing standards of care for comprehensive Grampian Osteoporosis Service, based at Aberdeen Royal Infirmary, foot health management. Podiatrists are involved in screening and covers a population of 0.6 million spread over 3000 square miles of monitoring of the foot systems and education of patients to improve urban and rural communities, including the Shetland Isles and Orkney. awareness of the range of foot pathologies to facilitate early detection Until recently, patients living in these island communities were required and treatment. The emphasis on prophylactic treatment in early INVITED SPEAKER ABSTRACTS Tuesday 28 April 2015 i3

disease aims to maintain tissue viability and preserve lower limb and cultural factors on musculoskeletal pain. In general, the evidence function. Reducing mechanical overload on the foot with specific would suggest that if we are to make significant impact on work footwear, functional foot orthoses, splints and exercise therapy to disability, we need to take a broader view of prevention and develop improve strength and alignment helps to serve this aim. In more innovative solutions that impact on beliefs, expectations and psycho- established manifestations, accommodative orthoses are provided social factors among society and in workplaces. and, depending on local arrangements, pain relief with the use of Disclosure statement: The author has declared no conflicts of acupuncture, low-level laser and steroid injections are offered. interest. Treatment of nail and skin conditions, common with rheumatological conditions, is emphasized to preserve tissue viability and prevent secondary issues that may develop due to increased infection risk I17. VOCATIONAL REHABILITATION IN WORKERS WITH from immunocompromise. As part of the multidisciplinary team, INFLAMMATORY ARTHRITIS podiatrists generally receive referrals from Rheumatology and are Alison Hammond1 also well placed to pick up undiagnosed cases of RA in the 1Centre for Health Sciences Research, University of Salford, Salford, community. Podiatrists often link with physiotherapy and have a key UK role in referral of established cases for bespoke footwear or foot . Work disability is high in people with musculoskeletal conditions Disclosure statement: The author has declared no conflicts of (MSCs): occurring in 28–40% of people with RA; and 18-31% in AS. interest. Before becoming work disabled, people with MSCs experience considerable work instability, i.e. a mismatch between their abilities I14. SURGICAL MANAGEMENT OF THE FOOT AND ANKLE IN and job demands which threatens employment. Better medical RHEUMATOID ARTHRITIS treatment for RA and AS means more people should remain in employment. However, increased presenteeism (i.e. reduced at-work Steve Kriss1 productivity) occurs if people are struggling to manage work and their 1Podiatric Surgery, Royal Berkshire Hospital Foundation Trust, symptoms. Almost a quarter of working people with RA’s time at work Reading, UK is lost due to health problems and almost half reduce their pace of work and get help from colleagues. People experience work instability Abstract not provided. for a variety of reasons including job-related (e.g. unadapted work Disclosure statement: The author has declared no conflicts of environments and equipment, physical demands); psychological (e.g. interest. job strain; lack of knowledge/skills requesting job accommodations); and condition factors (e.g. hand function, pain, fatigue). Only a third of employed people have ready access to occupational health. Many I15. GUIDELINES FOR MANAGING FEET IN RHEUMATOID with arthritis are unwilling to disclose their condition at work. As a ARTHRITIS AND THE PROFESSIONAL CHALLENGES FACED result, many with arthritis may not receive help with work problems in Anita Williams1 their workplace. Vocational rehabilitation (VR) is a process to over- 1Directorate of Prosthetics, Orthotics and Podiatry, University of come barriers to remaining in work. People with RA with workplace Salford, Manchester, UK ergonomic modifications are 2.5 times less likely to stop work and early interventions can help reduce job loss. However, many employ- This presentation will focus on the research that has been done over ees with arthritis, and employers, are unaware of VR services to help the last decade and how it has significantly influenced the develop- job retention. This presentation will: briefly summarize common work ment of guidelines for the management of people with foot and ankle problems experienced by people with inflammatory conditions; review problems. Aligned with this has been the growth of specialist trials evaluating VR in inflammatory conditions; and discuss a podiatrists with the increasing profile of podiatry within rheumatology feasibility trial evaluating job retention VR for employed people with and also the recognition within podiatry of rheumatology as a inflammatory arthritis, provided by Rheumatology occupational thera- specialism. The podiatrist’s role will be explored in the context of the pists. This will include the work assessment used, work problems challenges faced in the implementation of these guidelines and the identified, job accommodations implemented and trial results. changing focus of the delivery of podiatry services. The patient’s Implications for future research and practice will be considered. pathway from identification of foot problems to their management will Disclosure statement: The author has declared no conflicts of interest. be described in relation to both positive outcomes and risks if the podiatrists input into the multidisciplinary team is reduced or removed. I18. PATIENT PERSPECTIVES ON VOCATIONAL Disclosure statement: The author has declared no conflicts of REHABILITATION PROVISION interest. Yeliz Prior1 1Centre for Health Sciences Research, University of Salford, Manchester, UK

Work problems are common among patients with inflammatory forms of arthritis (e.g. RA, PA, undifferentiated inflammatory arthritis) with RA MUSCULOSKELETAL HEALTH AND being the commonest long-term severe disabling condition in the UK. VOCATIONAL REHABILITATION Research suggests that work status, health, well-being and income are strongly related. RA related work instability can lead to work disability, and later to job loss. Loss of valued activities such as work could result in reduced self-esteem, life satisfaction, perceived health status and I16. MUSCULOSKELETAL DISORDERS IN WORKERS: WHO higher levels of depression and pain in people with RA. In the long IS AT RISK AND WHICH FACTORS MATTER: REPETITIVE term, these factors are associated with worse functional status, STRAIN, PSYCHOSOCIAL OR CULTURAL? disease outcome and increased health service use. Vocational rehabilitation is a process to overcome the barriers individuals with Karen Walker-Bone1 work instability or disability counter when accessing, remaining or 1MRC Lifecourse Epidemiology Unit, University of Southampton, returning to work. In the context of health care provision, this could Southampton, UK include practical advice and support to enable participants to disclose their condition to their employers, job modifications or accommoda- Musculoskeletal disorders are responsible for a considerable propor- tions such as ergonomic changes, psychosocial and informational tion of workplace disability in Europe, costing an estimated 2% of strategies, and multidisciplinary team referral to manage the condition. gross domestic product annually. Government statistics suggest that It is recommended that early intervention either when the person is still the requirement for disablement benefits is increasing. Some of these working and experiencing difficulties, or in the first few weeks of sick conditions are attributed to work and therefore strategies for leave, delivered in a format convenient to the patient is likely to result in prevention have generally focussed on reducing physical workplace better outcomes, such as reduced job loss. Thus, it is preferable to strain with ergonomic interventions. However, existing prevention help people stay at work, as research suggests that once out of work strategies have failed to make impact on the burden from these people with inflammatory arthritis are much less likely to go back to conditions. This talk will put forward explanations as to why ergonomic employment. In order to deliver vocational rehabilitation to employed interventions might not be resolving the problems. Historical epide- patients in a format convenient to the patient requires individualized miological data on mechanical low back pain will be presented as well treatment. Thus it is important to understand the patient’s experience as international studies of the effects of psychosocial, psychological of undergoing vocational rehabilitation to help plan and deliver job i4 Tuesday 28 April 2015 INVITED SPEAKER ABSTRACTS

retention interventions to patients with rheumatological conditions. This care, and patients often believe that little can be done. Evidence presentation will provide an overview of studies investigating people suggests that management of patients presenting with OA is not in line with inflammatory arthritis’ experience of undergoing vocational with published guidance and core treatments such as exercise are not rehabilitation. It will focus on employed people with work problems, routinely offered early on in the course of the condition, indicating that wanting to stay at work, with particular reference to the qualitative there is a need to improve and optimize care of people with OA. There interviews conducted with participants in the Work Rehabilitation in is limited evidence as to the best way to deliver core treatments such Inflammatory Arthritis Study (WORK-IA). Factors such as access to as exercise, particularly when considering who should deliver exercise vocational rehabilitation, and the barriers to and facilitators for staying advice and prescription and where it should be delivered. Previous at work will be discussed using participants’ narratives. research has demonstrated that exercise interventions delivered by Funding: The WORK-IA study is funded by the Arthritis Research UK. health care professionals were found not to have significantly different Disclosure statement: The author has declared no conflicts of effects compared with interventions delivered by non-health care interest. professionals, suggesting both can produce positive changes in exercise levels. Patients are sometimes reluctant to seek help for OA, considering it to be simply part of the ageing process. Studies have shown that among patients consulting for knee OA, less than half had tried exercise as a treatment and this was mostly self- rather than doctor-initiated. Clearly there is a need to increase the uptake of MAKING IT HAPPEN: OPTIMIZING THE exercise and appropriately support those with OA to become more active. A broader community based approach e.g. health trainers, SERVICE TO RA PATIENTS exercise/sport science graduates, qualified gym instructors, may be a viable option. This session will examine the need and potential for community based, non-healthcare professional facilitated exercise programmes, specifically for those with OA. This session will also I19. OPTIMIZING THE FINANCE AND ORGANIZATION identify current community based roles that may be suitable to support individuals with OA to manage their condition through exercise and 1 Alan Hakim examine the potential training needs for such roles. 1 Non-executive, CWHHE Clinical Commissioning, Inner North West Disclosure statement: E.L.H. is part-funded by the National Institute London, London, UK for Health Research Collaborations for Leadership in Applied Health Research and Care West Midlands. Abstract not provided. Disclosure statement: A.H. has served as a board member of the CWHHE Clinical Commissioning, London; has provided consultancy I23. COMMUNITY-BASED EXERCISE PROGRAMMES LED services to the Hypermobility Unit, The Hospital of St John and St BY NON-HEALTHCARE EXERCISE PROFESSIONALS FOR Elizabeth; has received royalties from Hypermobility, Fibromyalgia and OSTEOARTHRITIS: A COCHRANE REVIEW Chronic Pain, Churchill Livingston; has received honoraria for Nicola Walsh1 Masterclass training in hypermobility syndromes; has received 1 research support from the National Lottery; and provided volunteer University of the West of England, Bristol, UK training to the HMSA. OA is predicted to become the 4th leading cause of worldwide disability by 2020 as the population ages, becomes heavier and more inactive. I20. OPTIMIZING THE DRUGS Currently 8.5 million people in the UK are affected by OA. Evidence- based guidelines recommend exercise as a core modality to reduce Bruce Kirkham1 pain and increase function; healthcare professionals are ideally placed 1Rheumatology Department, Guy’s and St Thomas’ NHS Foundation and appropriately skilled to provide this advice, but timely access to Trust, London, UK NHS treatment is a growing problem in the face of increasing referrals and limited resources. As such, a strategic healthcare and Abstract not provided. approach to long-term management is required to ensure people Disclosure statement: The author has declared no conflicts of interest. receive timely access to effective interventions. Current lack of access may contribute to the problem of almost half of people with OA I21. OPTIMIZING THE PATIENT ROLE reporting they do no exercise or physical activity to help their condition. Previous Cochrane reviews evaluating the effectiveness of land- and 1 David Walker water-based exercise interventions for OA conclude that short-term 1 Muskuloskelatal Unit, Freeman Hospital, Newcastle upon Tyne, UK benefits in pain and function are gained, particularly in the knee joint, whilst the evidence for the effects in the hip joint are less conclusive, Abstract not provided. notably for functional improvements. Evidence synthesis also suggests Disclosure statement: The author has declared no conflicts of that in the short-term supervised regimens effect greater benefit interest. although home-based interventions tend to result in greater adherence in the long-term, although these outcomes are based on other chronic diseases as no studies in OA met the inclusion criteria. No evidence synthesis exists regarding the effectiveness of exercise by community based, non-healthcare professionals. This Cochrane review analysed the evidence for community based, non-healthcare professional COMMUNITY-BASED PHYSICAL facilitated exercise programmes. The primary outcomes of interest were pain and function; secondary outcomes included physical activity ACTIVITY FOR OSTEOARTHRITIS: THE levels, quality of life, long-term engagement and cost effectiveness. EMERGING ROLE OF NON-HEALTHCARE This session will include details of the findings of the Cochrane review, including the outcome and quality of the supporting evidence, and cost- PROFESSIONALS effectiveness of the interventions. Implications for potential models of care will be discussed in light of the evidence. Disclosure statement: N.W. has received an Arthritis Research UK Career Development Fellowship. I22. COMMUNITY-BASED PHYSICAL ACTIVITY FOR OSTEOARTHRITIS: THE EMERGING ROLE OF NON- HEALTHCARE PROFESSIONALS I24. LESSONS LEARNED FROM CARDIAC REHABILITATION: APPLICATION TO OA Emma L. Healey1 1Research Institute for Primary Care & Health Sciences, Primary Care John Buckley1 1 Sciences, Staffordshire, UK Department of Clinical Sciences & Nutrition, University of Chester, Chester, UK OA is a highly prevalent condition in primary care, and management guidelines were published in the UK by the National Institute for Health Abstract not provided. and Care Excellence in 2008 and revised in 2014. Despite its Disclosure statement: The author has declared no conflicts of prevalence, OA management is not seen as a high priority for primary interest. INVITED SPEAKER ABSTRACTS Tuesday 28 April 2015 i5

has received educational funds (less than £1000 each) to attend medical/scientific conferences from Pfizer, Schering-Plough, Chugai, POST-DOCTORAL, PHD AND Merck and UCB Foundation; and has served on scientific advisory POSTGRADUATE STUDENT NETWORK boards for MedImmune, Takeda, Pfizer and Sanofi.

Garrod Prize Winner

I25. MENTORING FOR THE MENTEE I29. GUT-MICROBIOTA INDUCED IL-1B AND IL-6 CONTROL 1 THE DIFFERENTIATION OF REGULATORY B CELLS Jo Adams 1 1 Elizabeth Rosser Occupational Therapy, University of Southampton, Southampton, 1 UK Rheumatology Research, University College London, London, UK

This presentation will consider the role and scope of a mentor and B cells are thought to be pathogenic in autoimmune disease due to mentee in clinical academic practice. Identifying key attributes of a their ability to produce autoantibodies. However, administration of B possible mentor for different stages in academic progression is cell depleting agents in autoimmunity has led to heterogeneous clinical discussed and the skills that a mentor may use to help support and responses ranging from complete and sustained remission in some facilitate development are considered. Tools that may be useful in patients to treatment failure in others. Previous work by our laboratory some contexts of personal academic mentoring are presented has shown that a subset of B cells known as regulatory B cells (Bregs) alongside signposting mentoring schemes already in practice. can suppress inflammation via the provision of IL-10. In the context of Disclosure statement: The author has declared no conflicts of interest. experimental arthritis, Bregs suppress joint inflammation by preventing the expansion of pathogenic T cells. This suggests that non-specific targeting of B cells may also deplete beneficial populations of cells. We I26. MENTORING CASE STUDIES IN RHEUMATOLOGY believe that by understanding the fundamental biological processes that control Breg induction and function, we may be able to improve Fiona Cramp1 current treatment regimes, leading to a better long-term prognosis for 1Faculty of Health and Applied Sciences, University of the West of disease. More recently, we have demonstrated that Bregs arise in England, Bristol, UK response to inflammatory cytokines, namely IL-1b and IL-6, produced in response to pro-arthritogenic stimuli and the constituents of the gut This short presentation will provide examples of how mentoring has microflora. Drastic alteration imposed on the microbiota by treatment been used successfully within a rheumatology setting to support with antibiotics causes a reduction in IL-1b and IL-6, and concurrently postgraduate research students and postdoctoral researchers. in the number and functional capacity of Bregs. Furthermore, we found Benefits and challenges from the perspective of the mentor and that mice lacking IL-6R or IL-1R1 exclusively on B cells have a reduced mentee will be considered and tips provided to promote successful number of IL-10-producing B cells, and developed an exacerbated mentoring partnerships. The presentation will be followed by inter- arthritis compared with control animals. Taken together, these active small group discussions with senior academics to identify data show that the host-symbiont relationship in the gut is not only individual benefits that could be obtained through mentoring. important in controlling inflammatory responses but also in the Disclosure statement: The author has declared no conflicts of interest. development of fully functional Bregs. Disclosure statement: The author has declared no conflicts of interest.

I30. THE COST OF TREATING JUVENILE IDIOPATHIC JEWELS IN THE CROWN ARTHRITIS IN THE ERA OF BIOLOGICS Wendy K. Gidman1, Linda Davies1, Roberto Carrasco2, Kimme Hyrich2, Wendy Thomson2 and Deborah Symmons1 1Manchester Centre for Health Economics and 2Arthritis Research I27. A RHEUMATOLOGIST IN WHITEHALL Centre for Epidemiology, University of Manchester, Manchester, UK Mark Walport1 1Chief Scientific Adviser, HM Government, UK Background: Internationally healthcare funders have adopted strate- gies to prioritize spending due to spiralling healthcare costs. In the UK Abstract not provided. the National Institute for Health andCare Excellence (NICE) applies Disclosure: cost-effectiveness analyses (CEA). Few studies have estimated the cost of managing JIA. Specifically DMARDs, including MTX and biologics, are used early in the disease process. Evidence suggests that biologic medication is a major component of the cost associated Michael Mason Prize Winner with treating JIA. This analysis aims to estimate the costs over the first 3 years of treatment of JIA. I28. UK PRIMARY SJO¨ GREN’S SYNDROME REGISTRY Methods: The Childhood Arthritis Prospective Study (CAPS) was used 1 Wan-Fai Ng to estimate the direct costs of JIA treatment to the secondary care 1 Musculoskeletal Research Group, Newcastle University, Newcastle provider. CAPS is a longitudinal observational UK inception cohort upon Tyne, UK study following children with JIA from seven paediatric rheumatology centres. All participants who had completed 3 years of follow-up were Abstract not provided. included in this analysis. The ingredient approach was used. This Disclosure statement: W.N. has received speaker fees (less than involved estimating resource use and applying 2012–13 reference £2000 each) from Roche, Eisai (Korea) and UCB for engagements; costs. Total cost per patient and median cost per disease sub-group

I30 TABLE 1. Three-year costs of JIA per person by disease subgroup in pounds JIA subtype Three-year cost, median (minimum–maximum), pounds

Rheumatologist Referral to Clinical Laboratory Joint Traditional Biologic Total appointments other care imaging tests Injections DMARDS DMARDS All (n ¼ 849) 965 (233–13 409) 984 (0–8766) 0 (0–1752) 76 (19–1156) 1060 (0–8480) 8 (0–3091) 0 (0–46 840) 3901 (251–54 113) Systemic (n ¼ 48) 1802 (233–13 409) 864 (0–3252) 22 (0–1752) 267 (19–1156) 0 (0–2120) 106 (0–2419) 0 (0–37 160) 4456 (256–50 513) Oligoarthritis (n ¼ 370) 768 (233–10 425) 858 (0–8766) 0 (0–1036) 40 (0–516) 1060 (0– 5830) 0 (0–2154) 0 (0–26 423) 2881 (251–29 518) Extended Oligoarthritis (n ¼ 66) 1164 (233–4371) 1356 (0–4237) 22 (0–871) 104 (13–453) 1590 (0–8480) 40 (0–1880) 0 (0–46 840) 4893 (1077–53 063) Polyarthritis RF negative (n ¼ 198) 1189 (233–3864) 1230 (0–5275) 22 (0–1124) 135 (0–518) 1060 (0–4770) 70 (0–2635) 0 (0–36 242) 5221 (578–43 277) Polyarthritis RF positive (n ¼ 30) 743 (233–6510) 1648 (0–4138) 11 (0–381) 191 (54–613) 1060 (0– 3180) 604 (0–3091) 0 (0–44 749) 6434 (1019–54 113) Enthesitis related (n ¼ 40) 1034 (233–5273) 1330 (0–3972) 22 (0–970) 83 (2–492) 530 (0–3180) 93 (0–2618) 0 (0–31 943) 4523 (701–38 179) Psoriatic (n ¼ 60) 1001 (233–9289) 832 (0–8742) 0 (0–821) 87 (0–348) 1060 (0–4240) 60 (0–2521) 0 (0–32713) 4016 (275–36 145) Undifferentiated (n ¼ 18) 499 (233–2228) 858 (0–2520) 0 (0–259) 38 (11–271) 530 (0–1590) 0 (0–146) 0 (0–14 157) 2165 (712–18 895) Other inflammatory arthritis (n ¼ 19) 632 (233–5204) 785 (0–3252) 22 (0–672) 72 (0–269) 0 (0–2120) 0 (0–2002) 0 (0–16 982) 3901 (251–54 113) i6 Tuesday 28 April 2015 INVITED SPEAKER ABSTRACTS

were calculated. Cost data were highly positively skewed therefore non-parametric tests were used to explore the predictors of costs. Young Investigator Award Results: The sample comprised 849 children: 542 were female and the mean age at study enrolment was 7.6 years. Table 1 outlines the I32. SYNOVIAL PATHOTYPE PREDICTS RESPONSE TO TNF- breakdown of costs by ILAR subtype and cost category. Costs ALPHA INHIBITORS IN PATIENTS WITH RHEUMATOID ARTHRITIS associated with treating JIA are highly variable. The median 3-year 1 1 1 1 treatment cost was £3901, although costs ranged from £251 to £54 Maria Di Cicco , Frances Humby , Stephen Kelly , Nora Ng , Arti Mahto1, Ilias Lazarou1, Rebecca E. Hands1, Vidalba Rocher1, 113. Biologic medication use was reported for every ILAR category. 1 1 1 Median treatment costs were significantly higher in those treated with Alessandra Nerviani , Lu Zou , Michele Bombardieri and Costantino Pitzalis1 biologics (P ¼ 0.0001). Additionally, the median cost of treating 1 children with JIA varied with ILAR category. Experimental Medicine and Rheumatology, Queen Mary University Conclusion: Those involved in providing, developing and funding JIA of London, London, UK health services should be aware that biologic medication and appointments with rheumatologists are the most costly aspects of Background: RA is characterized by high clinical variability, and care. Importantly, this analysis did not include indirect costs incurred predicting response to treatment is challenging. The identification of by parents and patients or productivity losses. Whilst this accords with biomarkers of clinical outcome to guide therapeutic decisions is NICE approaches to costing, it is likely to significantly underestimate therefore needed. As well as clinical variability, RA shows high the true societal cost of treating JIA. biological heterogeneity. With specific regard to the synoviumthe Disclosure statement: W.K.G. has received a Research Methods primary target of the diseasewe have identified three distinct Fellowship from the National Institute for Health Research. All other histopathotypes; the question arises whether a specific synovial authors have declared no conflicts of interest. pathotype may translate into different outcomes and response to treatment. This study aims to investigate whether the synovial pathotype is associated with clinical response to TNFa inhibitors (TNFis), specifically the pegylated mAb certolizumab pegol. I31. ECONOMIC EVALUATION OF A BRIEF EDUCATION, Methods: 28 consecutive biologic-nay¨ ve RA patients qualifying for SELF-MANAGEMENT AND UPPER LIMB EXERCISE TRAINING TNFi according to National Institute for Health and Care Excellence PROGRAMME IN PEOPLE WITH RHEUMATOID ARTHRITIS guidance were recruited at Barts and the London Hospital. Patients

1 2 2 underwent US-guided synovial biopsy of an active joint prior to Lindsay M. Bearne , Billingsley Kaambwa , Julie Ratcliffe , commencing therapy. Sections of synovial tissue were treated by Ernest Choy3, David L. Scott4, Michael V. Hurley5 and Victoria 1 haematoxylin and eosin staining and immunohistochemical staining for L. Manning CD20, CD3, CD68sl and CD138 and graded as either diffuse or 1Division of Health and Social Care Research, King’s College 2 aggregate infiltrate, as previously described. Samples were then London, London, UK, Flinders Health Economics Group, School of classified as lymphoid (presence of lymphocytic aggregates resem- Medicine, Flinders University, Adelaide, Australia, 3Institute of 4 bling ectopic lymphoneogenesis), myeloid (absence of aggregates and Infection & Immunity, Cardiff University, Cardiff, Department of predominant sublining macrophagic infiltrate) or Pauci immune Rheumatology, Faculty of Life Sciences and Medicine, King’s (absence of both aggregates and sublining macrophagic infiltrate). 5 College London and School of Rehabilitation Sciences, St George’s, US of 12 joints (wrists and 10 MCPs) was also performed and images University of London and Kingston University, London, UK scored for synovial thickening (ST) and power Doppler according to the OMERACT semi-quantitative scoring system. After 3 months, Background: The Education, Self-management and Global Upper response to treatment was assessed according to EULAR response Limb Exercise Training for people with RA (EXTRA) programme criteria. US was repeated and the mean fall in ST and power Doppler comprises four 1-h supervised group (4–6 participants) education, evaluated. A second synovial biopsy from the same joint was obtained self-management and functional global upper limb exercise training for 18 patients. The study received local ethics approval. sessions (delivered twice weekly for the first 2 weeks), supplementing Results: 13 patients (46.4%) showed Pauci immune, 4 (14.3%) a daily home exercise regimen. It improves upper limb disability, showed myeloid and 11 (39.3%) showed a lymphoid pattern at function, strength and arthritis self-efficacy compared with usual care, baseline. Clinical characteristics of patients were comparable among with no adverse effects on disease activity at 12 weeks. The aim of this the three synovial pathotype groups. A significantly higher proportion study was to conduct an economic evaluation of the EXTRA of patients with lymphoid pattern achieved a EULAR response (Pauci programme compared with usual care. immume 46%, myeloid 75%, lymphoid 100%, P = 0.014) despite a Methods: The economic evaluation was conducted alongside an lower use of oral steroids (P = 0.005), as well as higher mean fall in DAS assessor-blind, randomized controlled trial (ISRCTN: 14268051, for 28 joints (DAS28), ST and power Doppler (P < 0.05). Interestingly, ethical approval: 08/H0808/118) that recruited and randomized the response was associated with a higher fall in sublining macro- participants, between February 2009 and September 2010. All phages count (P = 0.05), highlighting the potential role of this participants gave informed consent. A cost–utility analysis was parameter as a biomarker of response. Stepwise logistic regression conducted with 108 participants randomized to either the EXTRA analysis performed by entering several baseline variables (gender, programme (n ¼ 52) or usual care (n ¼ 56). The primary outcome for the age, disease duration, erosive and antibody status, use of steroids, economic analysis was quality adjusted life-year (QALY) gains DAS28, HAQ and synovial pathotype) identified synovial pathotype as calculated from the EuroQol five-dimension three-level (EQ-5D-3L) a potential predictor of response, with a significantly higher chance of questionnaire responses at baseline and 12 and 36 weeks. Data on achieving EULAR response in the lymphoid group (P < 0.05). resource use and costs (including interventions, medication, primary Conclusion: Our work shows that synovial pathotype is significantly and secondary care contacts, private healthcare and social care) were associated with clinical and US response to TNFi treatment, suggest- collected using a customized Client Recipient Service Inventory. A ing that histopathology could be considered as a potential key tool to healthcare perspective was assumed for the primary analysis with a guide therapeutic decisions for RA patients. 36-week follow-up period for both costs and outcomes. Disclosure statement: The authors have declared no conflicts of Results: Compared with usual care, the EXTRA programme was interest. associated with higher incremental QALY gains (0.0296 QALYs) and slightly higher costs (£82), resulting in an incremental cost-effective- ness ratio of £2770 per additional QALY gained. Thus, the EXTRA programme was cost-effective from an NHS perspective when assessed against the current NICE threshold of £20 000–£30 000/ HEBERDEN ROUND QALY gained. When a wider cost perspective was considered (including private and social care/local authority costs), the EXTRA programme became both less costly and more effective, indicating that it dominated usual care. These findings were robust to sensitivity I33. LUPUS AND THE ART OF CLINICAL MEDICINE analyses including accounting for missing data and removing cost outliers. David D’Cruz1 Conclusion: The physiotherapist-led EXTRA programme is clinically 1Louise Coote Lupus Unit, St Thomas’ Hospital, London, UK effective and represents a cost-effective use of resources compared with usual care and leads to lower healthcare costs and work absence. William Heberden was the outstanding clinician of his day who argued It may be easily implemented in practice as it requires little additional that ‘the must always be guided by his own direct therapist training and no specialized equipment. observation and his accumulating exposure’. His legacy is excellence Disclosure statement: The authors have declared no conflicts of in the practice of medicine: the art of observation, critical assessments interest. of observations and compassion for his patients. INVITED SPEAKER ABSTRACTS Tuesday 28 April 2015 i7

Despite huge technological advances in diagnostic tests and imaging, and colleagues in 1948, the introduction of corticosteroid therapy by rheumatology remains a very clinical discipline. SLE is a complex Hench in the same year and the development of cytotoxic in autoimmune rheumatic disease the diagnosis and management of the mid-20th century heralded the modern era of this disorder. Since which exemplifies William Heberden’s exhortations to critically then, there have been astounding advances in the understanding of observe patients with detailed histories and physical examinations the immunopathogenesis of SLE, leading to the era of biologic both at presentation and throughout the often complex disease therapies such as rituximab and belimumab which are currently in course. Although there is no record that Heberden was aware of lupus fashion and widely used. We should however remember Heberden’s as we know it today, he was familiar with Peruvian bark (cinchona) as a maxim: ‘For new , and new methods of cure, always work treatment for malaria, preceding Dr J. F. Payne’s first description of the miracles for a while’. use of quinine to treat lupus at St Thomas’ Hospital, London in 1894. Disclosure statement: D.D’C has received honoraria from The discovery of the LE cell as a diagnostic test for SLE by Hargraves GlaxoSmithKline, Roche and Lilly. i8 Wednesday 29 April 2015 INVITED SPEAKER ABSTRACTS

I35. BIOLOGIC AGENTS IN THE TREATMENT OF PAIN IN THE 21ST CENTURY: MUSCULOSKELETAL PAIN SENSORY–IMMUNE INTERACTIONS, Nidhi Sofat1 1Rheumatology, St George’s, University of London, London, UK BIOLOGIC AGENTS AND BISPHOSPHONATES OA and RA are the predominant arthritides worldwide, resulting in a high degree of functional impairment and reduced quality of life owing to chronic pain. To date, a large focus has been placed on achieving disease modification in arthritic disorders, with an aim to halt disease progression. An increasing area of unmet need in patient I34. SENSORY–IMMUNE INTERACTIONS AND THE ROLE OF symptom management is pain. Current treatments are aiming to NEUROPEPTIDES IN A SERUM TRANSFER INDUCED MOUSE modulate pain include NSAIDs, opiates and, more recently, centrally MODEL OF INFLAMMATORY ARTHRITIS acting pharmacotherapies to avert pain. This presentation will focus on the rationale for new avenues in pain modulation, including Zsuzsanna Helyes1 inhibition with anti-nerve growth factor antibodies and centrally acting 1Department of Pharmacology and Pharmacotherapy & Szenta´ gothai analgesics. The author will also consider the potential for structure Research Centre, University of Pe´ cs, Pe´ cs, Hungary modification in cartilage/bone using growth factors and stem cell therapies to ultimately achieve pain modulation. The possible Objective: The serum-transfer arthritis is a widely-used translational mismatch between structural change and pain perception will also mouse model of RA, in which the immunological components have be discussed, introducing recent techniques that may assist in thoroughly been investigated. In contrast, little is known about the role improved patient phenotyping of pain subsets in RA and OA. Such of sensory neural factors, neuropeptides and the complexity of neuro- developments could help further stratify subgroups and treatments immune interactions. Therefore, we analysed the involvement of for people with arthritis in future. capsaicin-sensitive peptidergic sensory nerves, and the neuropeptides Disclosure statement: The author has declared no conflicts of pituitary adenylate-cyclase activating polypeptide (PACAP), as well as interest. the tachykinins substance P/neurokinin A (SP/NKA) and haemokinin-1 (HK-1). These peptides are expressed in sensory neurons and immune I36. TREATING BONE TO MANAGE PAIN cells, and they are known to modulate vascular and cellular inflammatory mechanisms. Philip Conaghan1 Methods: Polyarthritis was induced by i.p. injection of the arthrito- 1Chapel Allerton Hospital, Leeds, UK genic K/BxN serum. Resiniferatoxin (RTX) pretreatment was performed –/– to inactivate capsaicin-sensitive nerves. Gene-deficient mice (Tac1 , Abstract not provided. where SP/NKA are missing; Tac4/–, where HK-1 is absent; or –/– Disclosure statement: P.C. is a member of speakers’ bureaus for PACAP ) were used to analyse the roles of the respective peptides. AbbVie, AstraZeneca, Bioiberica, Bristol-Myers Squibb, Centocor, Oedema, touch sensitivity, noxious heat threshold, joint function and Janssen, Merck Pharmaceuticals, Novartis, Pfizer, Roche, UCB; and clinical arthritis severity scores were determined repeatedly through- has received research support from Centocor Research and out two weeks. Micro-CT to detect bone morphological alterations, Development and Pfizer. in vivo optical imaging to quantify MMP and neutrophil-derived MPO activities, semiquantitative histopathological scoring and radioimmu- noassay to measure somatostatin in the joint homogenates were also performed. Results: In RTX-pretreated mice, autoantibody-induced joint swelling, arthritis severity score, and MMP and MPO activities, as well as histopathological alterations were significantly greater. Self-control quantification of the bone mass revealed decreased values in intact female mice, but significantly greater pathological bone formation after THE BRITISH SOCIETY FOR RTX pretreatment. Mechanical hyperalgesia from day 10 was smaller, and although thermal hyperalgesia did not develop, noxious heat IMMUNOLOGY: NOT THE USUAL threshold was significantly higher following defunctionalization of the SUSPECTS: NOVEL PLAYERS IN IMMUNE capsaicin-sensitive peptidergic nerves. Somatostatin-like immunor- eactivity elevated in the tibiotarsal joints in non-pretreated, but not in HOMEOSTASIS RTX-pretreated mice. There was no change in any arthritic symptoms in Tac1–/ animals. In Tac4/ mice joint swelling, hyperalgesia and histopathological alterations were significantly smaller compared with WT animals, but MPO activity was not altered. In PACAP/ mice, I37. UNCONVENTIONAL T CELLS clinical score and oedema were significantly reduced, mechanical 1 Jessica Strid hyperalgesia and motor impairment were absent, metabolic activity 1 Centre for Complement & Inflammation Research, Imperial College and superoxide production were significantly less, MPO activity was London, London, UK significantly lower in the early, but greater in the late phase. Synovial hyperplasia was significantly greater and progressive bone spur Abstract not provided. formation was only observed in PACAP-deficient mice. Conclusion: Although capsaicin-sensitive sensory nerves mediate Disclosure statement: The author has declared no conflicts of mechanical hyperalgesia in the later phase of autoantibody-induced interest. chronic arthritis, they play important anti-inflammatory roles at least partially through somatostatin release. Although the tachykinins SP/ I38. INNATE LYMPHOID CELLS AND STROMA IN NKA are not involved in this immune arthritis model, HK-1 is an INFLAMMATION AND TISSUE PATHOLOGY important mediator of joint inflammation and the consequent pain. 1 PACAP increases swelling, vascular leakage, hyperalgesia and early Mark Coles 1 inflammatory cell accumulation, but decreases immune cell functions Centre for Immunology and Infection, Department of Biology, and bone neoformation in the late phase. Identification of their targets University of York, UK and the receptor mechanisms can open novel perspectives in arthritis therapy. Abstract not provided. Disclosure statement: Z.H. has received research support from Disclosure statement: M.C is the Chief Scientific Officer and a Hungarian Brain Research Programme B. shareholder of Simomics Ltd. INVITED SPEAKER ABSTRACTS Wednesday 29 April 2015 i9

I39. NKT CELLS I42. THE NEUROLOGICAL MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS Mark Exley1 1Manchester Collaborative Centre for Inflammation Research, David D’Cruz1 University of Manchester, Manchester, UK 1Louise Coote Lupus Unit, St Thomas’ Hospital, London, UK

Abstract not provided. SLE is a complex autoimmune rheumatic disease characterized by Disclosure statement: M.E. has a small amount of equity in NKT multisystem involvement in the context of autoantibodies to nuclear Therapeutics, Inc.; has a consultancy agreement with Agenus; has antigens. Neurological involvement is common and is classified received research funding from AstraZeneca, GSK and the University clinically into peripheral and CNS disease. The ACR nomenclature for of Manchester; and receives a small fraction of the royalties paid to NPSLE provides case definitions for 19 neuropsychiatric lupus Harvard Hospital for patent licence as part of the same syndromes, with reporting standards and recommendations for interaction with NKT Therapeutics, Inc. laboratory and imaging tests. The pathogenesis of these complica- tions, especially CNS disease, remains poorly understood and, given that severe CNS disease is an exclusion criterion in all major therapeutic trials, treatment options are empirical. The presenting clinical features of neurological manifestations range from very subtle neuropsychiatric symptoms through to seizures, psychosis and ESSENTIALS IN RHEUMATOLOGY: severe peripheral neuropathies. Differentiating mild psychiatric/ psychological symptoms due to lupus from secondary effects of DISEASE ASSESSMENT AND having a chronic debilitating disorder can be very challenging and MANAGEMENT imaging investigations are usually unhelpful. SLE may also be associated with aPLs, which may lead to cerebral thrombotic features as well as seizures and cognitive dysfunction. Treatment of aPL-mediated clinical features is with anticoagulation rather than I40. THE ASSESSMENT AND MANAGEMENT OF RAYNAUD’S immunosuppression. Disclosure statement: The author has declared no conflicts of Ariane Herrick1 interest. 1Arthritis Research UK Epidemiology Unit, Salford Royal NHS Foundation Trust, Manchester, UK

RP is most commonly primary (i.e. idiopathic). A defining feature of primary RP is that it does not progress to irreversible tissue injury, and it is therefore often considered benign. However, when severe, primary QUALITY NOT QUANTITY: RESEARCH RP can be very distressing and can limit activities. In contrast, when RP is secondary to an underlying cause, for example connective tissue TRAINING IN QUALITATIVE METHODS disease, it can progress to irreversible tissue injury with ulceration and sometimes gangrene. Therefore when assessing a patient with RP, the first question for the rheumatologist is Why does this person have RP? The second question is What is the best approach to management? I43. HOW TO BAKE THE QUALITATIVE CAKE: WHICH This session will cover diagnosis (history, examination, investigations METHOD TO USE? including capillaroscopy) and management of RP, including RP which Elizabeth Hale1 has progressed to digital ulceration and/or critical ischaemia. 1Rheumatology, Dudley Group of Hospitals, Birmingham, UK Treatment options will be discussed including conservative (non- drug) measures, vasodilator therapies (including phosphodiesterase Abstract not provided. inhibitors and endothelin-1 receptor antagonists), and surgery. These Disclosure statement: The author has declared no conflicts of options will be put into context by a series of short case histories, and interest. by presentation of the UK Systemic Sclerosis Study Group consensus best practice pathways for RP and for systemic sclerosis-related digital ulceration and critical ischaemia. By the end of the session, I44. ME, MYSELF AND MY PARTICIPANT: RIGOUR AND participants should be able to assess the patient presenting with RP, REFLEXIVITY IN QUALITATIVE RESEARCH including differentiating between primary and secondary RP; discuss Caroline A. Flurey1 the role of capillaroscopy in the assessment of RP; and describe the 1 different management options for RP, including RP complicated by Faculty of Health and Applied Sciences, University of the West of digital ulceration or critical ischaemia. England, Bristol, UK Disclosure statement: A.H. has undertaken consultancy work for Actelion and spoken at meetings sponsored by Actelion. Qualitative research involves interaction between the participant(s) and the researcher. It is therefore important to acknowledge the back- ground and perspective that the researcher brings to the interview or I41. AN APPROACH TO PATIENTS WITH A CHRONIC focus group and the effect that their background has on the way that MONOARTHRITIS they analyse the data. This presentation will explain the importance of being reflexive in qualitative research and explore other ways that we Neil H. Snowden1 can ensure qualitative work is rigorous. This presentation will also 1Department of Rheumatology, Pennine MSK Partnership/Pennine include an example of a patient co-facilitating the focus groups and Acute NHS Trust, Oldham, UK discuss the affect this had on the focus group discussion. Disclosure statement: C.A.F. has received research support from Chronic monoarticular inflammation is common and can present both Arthritis Research UK. diagnostic and therapeutic challenges. Diagnostically, most cases are non-infective and can be considered as part of the spectrum of SpA. However, a minority of cases will be caused by chronic infection, I45. OVERCOMING ANALYSIS PARALYSIS: WORKING OUT particularly tuberculosis, and on occasion synovial tumours. Non- WHAT TO DO WITH YOUR DATA infective inflammation may also sometimes point to systemic disease. Karen Rodham1 SF analysis and sometimes biopsy are crucial in making a diagnosis. 1 Therapy of non-infective cases may require no more than injection of School of Psychology, Staffordshire University, Stoke-on-Trent, UK corticosteroids, but resistant cases may require further local, systemic or occasionally surgical intervention. A framework for diagnosis and Abstract not provided. management will be presented. Disclosure statement: The author has declared no conflicts of Disclosure statement: The author has declared no conflicts of interest. interest. i10 Wednesday 29 April 2015 INVITED SPEAKER ABSTRACTS

COMORBIDITIES IN RHEUMATOID BHPR WORKSHOP: MEASURING ARTHRITIS DISEASE ACTIVITY IN AXIAL SPONDYLOARTHROPATHY AND ANKYLOSING SPONDYLITIS I46. THE IMPACT OF COMORBIDITY ON OUTCOMES AND PROGNOSIS IN RA Elena Nikiphorou1 1 I50. AXIAL SPONDYLITIS: WHY MEASURE DISEASE Addenbrooke’s Hospital, Cambridge University Hospitals NHS ACTIVITY AND WHAT SHOULD WE AIM TO ACHIEVE? Trust, Cambridge, UK Alexander Bennett1 The need to better understand and quantify the impact of 1Defence Medical Rehabilitation Centre, Academic Department of comorbidity on patients and survival is well recognized and forms Military Rehabilitation, Epsom, UK an important and topical area for research. Comorbidities add to the burden of disease, its complexity and management with implications The lecture will cover the different measures of disease activity used in on the patient’s quality of life, as well as health care resource axial SpA, including patient-reported outcomes, laboratory tests and utilization and overall costs. The presence of comorbidity will imaging. The current recommended disease measures will be inevitably affect the treatment given to a patient and therefore compared and the benefits of measuring disease activity and potential forms a core part of the management decisions. Premature mortality future disease measures will be discussed. is a recognized consequence of both comorbidities and extra- Disclosure statement: The author has declared no conflicts of interest. articular manifestations. Longitudinal observational studies provide an ideal setting for examining comorbidities and their impact on both I51. EXERCISES FOR AS PATIENTS short-term and longer-term outcomes, unlike randomized controlled trials which tend to have stringent inclusion and exclusion criteria, Sue Gurden1 lower patient numbers and shorter follow-up. The more the 1Physiotherapy, Aneurin Bevan University Health Board, Newport, UK comorbidities the worse the impact on patient and disease outcomes including mortality and therefore early recognition and management AS is a chronic systemic disease with a wide spectrum of disease of comorbidities is essential in reducing the disease burden and processes and symptoms. Historically, exercise has played a key role improving overall prognosis. Comorbidity is thus important in in the treatment and management of people with AS. Physical estimating patient outcomes and prognosis; in statistical analyses, exercises of various modalities have positive effects on metrology: it helps in the adjustment of confounders and outcomes data. It can disease activity, function, pain and psychological status. However, affect choice of treatment and is relevant in Stratified Medicines (e.g. changing symptomology and physical challenges can make it difficult based on patterns of different biomarkers in the presence of to find appropriate forms of training and exercise. The session will take comorbid conditions). Sometimes it will direct cessation of ongoing the form of interactive debate and will be facilitated towards therapies, while in other instances addition of other therapies may be progression of thoughtful planning of exercise programmes and will required (treatment adjustment). It therefore helps provide safe and review the current literature evidencing the use of exercise generally efficient treatment, improving the overall quality of care. In addition, it and specifically to this condition; discuss disease symptoms relevant can provide insights into disease aetiology and pathogenesis and to the appropriate use of exercise; and explore exercise facilities and improve our overall understanding of disease. motivational methods in order to encourage self-management, Disclosure statement: E.N. has received funding from ERAS, ERAN potentially using best practice examples from the group. The group and CLRN. will be expected to devise and demonstrate example exercises relevant to these discussions, therefore suitable clothing for this purpose is recommended. I47. COLLECTING AND RECORDING COMORBIDITY DATA Disclosure statement: The author has received speaker fees from USING THE CLINICAL PRACTICE RESEARCH DATALINK AbbVie, Pfizer and UCB. Jackie Cassell1 1Primary Care Epidemiology, Brighton and Sussex University, I52. OUTCOME MEASURES FOR AXSPA AND AS: A Brighton, UK PRACTICAL GUIDE

1 Abstract not provided. Kate Gadsby 1AbbVie, Derby, UK Disclosure statement: J.C. is a member of the Independent Scientific Advisory Committee for the Clinical Practice Research Datalink, This is a hands-on practical session looking at outcome measures used Medicines and Healthcare Regulatory Agency; is an Investigator in in clinical practice. We will look at the questionnaires and the evidence the Farr Institute (MRC funded), and has received research support for their use and application. There will also be the opportunity to score from the NIHR; and has received honoraria for reviewing work at the some of these to increase the confidence of the healthcare professional Wellcome Trust and the NIHR, and as Editor-in-Chief for the journal in using and interpreting them in the clinic setting Sexually Transmitted Infections. Disclosure statement: K.G. is a rheumatology nurse consultant for AbbVie; and has received honoraria prior to 2014 from a number of other companies for advisory work. I48. MENTAL HEALTH IN RA: AN OVERVIEW Ruth Williams1 1Wells Park Practice, London, UK I53. DEMONSTRATION OF METROLOGY (BASMI) AND ENTHESITIS (MASES) Abstract not provided. David Pickles1 Disclosure statement: The author has declared no conflicts of 1Rheumatology, Chapel Allerton Hospital, Leeds, UK interest. Abstract not provided. Disclosure statement: The author has declared no conflicts of interest. I49. ARUK-CSG COMORBIDITY WORKING GROUP: HARMONIZING COMORBIDITY DATA COLLECTION: WORK TO DATE I54. INTERACTIVE QUIZ Kimme L. Hyrich1 David Pickles1 1Rheumatology, University of Manchester, Manchester, UK 1Rheumatology, Chapel Allerton Hospital, Leeds, UK

Abstract not provided. Abstract not provided. Disclosure statement: The author has declared no conflicts of Disclosure statement: The author has declared no conflicts of interest. interest. INVITED SPEAKER ABSTRACTS Wednesday 29 April 2015 i11

Results: Psychological assessment: 14 papers including 3957 partici- pants, 1006 people with and 2951 controls without BJHS were eligible. HYPERMOBILITY: A PAIN TO MANAGE? People with BJHS experience significantly greater perceptions of, and more severe fear (P < 0.05), have a greater risk of demonstrating agoraphobia (P < 0.05), anxiety [OR 4.39 (CI 1.92, 10.40)], depression [OR 4.10 (95% CI 1.79, 9.41)] and panic disorders [OR 6.72 (95% CI I55. GENERALIZED HYPERMOBILITY IN THE PAEDIATRIC 2.22, 20.35)] than those without BJHS (P 0.005). Physiotherapy/ AND GENERAL POPULATION occupational therapy assessment: three clinical studies satisfied the eligibility criteria. Through this, evidence assessing the clinical out- Jacqui Clinch1 1 comes of using wrist/hand splints, proprioceptive-based exercises and Department of Paediatric and Adolescent rheumatology, Bristol general physiotherapy have been investigated. The data provides Royal Hospital for Children, University Hospitals Bristol, Bristol, UK limited support for the use of wrist/hand splints for school-children. Conclusion: Considerable emotional symptoms accompany BJHS. Abstract not provided. Further study is prioritized to explore how these results relate to non- Disclosure statement: The author has declared no conflicts of interest. Mediterranean populations. There is insufficient research exploring the clinical outcomes of a number of interventions including sensory integration, positioning and posture management and education. There I56. ZEBRAS AND AN INPATIENT is limited evidence on childhood populations both in psychological PROGRAMME comorbidities and physiotherapy/occupational therapy management. Helen Cohen1 Disclosure statement: The author has declared no conflicts of interest. 1Rheumatology, Pain & Rehabilitation, Royal National Orthopaedic Hospital, Stanmore, London, UK

Rheumatologists and allied health professionals working in muscu- loskeletal medicine will encounter many patients with joint hypermo- bility syndrome (JHS). In the majority of patients, this will be consistent with Ehlers–Danlos syndrome (EDS) type 3. However there are other rare genetic causes of joint laxity of which the clinician and therapist INFECTION AND AUTOIMMUNITY: THE need to be aware, as they may represent different challenges to treatment and rehabilitation. These may include other types of EDS MISSING LINKS such as classical (formerly types I and II), vascular (type IV) and kyphoscoliotic (type VI). Other genetic disorders also presenting with joint laxity include Marfan’s syndrome, Stickler’s syndrome and osteogenesis imperfecta. Chronic widespread musculoskeletal pain I58. PERIODONTAL DISEASE AND RHEUMATOID ARTHRITIS is well recognized in association with JHS. It can become severely Patrick Venables1 debilitating to the extent that patients may become immobile 1Musculoskeletal Medicine, NDORMS, University of Oxford, Oxford, UK depending on mobility aids such as crutches or wheelchairs, require help with activities of daily living and complain of recurrent joint Abstract not provided. subluxations and dislocations. In those with postural orthostatic Disclosure statement: The author has declared no conflicts of tachycardia syndrome, immobility and physical deconditioning may interest. aggravate symptoms. Concurrent psychological comorbidity such as anxiety, depression and personality disorders may also contribute to distress. Such complex cases may need a multidisciplinary pain I59. LEUCOCYTE IG-LIKE RECEPTORS: management and rehabilitation approach to begin to address their IMMUNOMODULATORS THAT PROVIDE A NOVEL long-term needs. This session will cover some of the rare genetic MECHANISM FOR MHC DISEASE ASSOCIATIONS? presentations of joint hypermobility, and considerations of an in- Rachel Allen1 patient multidisciplinary programme providing long-term self-manage- 1Institute for Infection & Immunity, St George’s, University of London, ment strategies. London, UK Disclosure statement: The author has declared no conflicts of interest. MHC class I (MHC-I) proteins have well-known disease associations in conditions ranging from infection to autoimmunity, with the most I57. OUTPATIENT PHYSIOTHERAPY AND THE striking association being that of HLA-B27 with spondyloarthritides. In COMORBIDITIES OF GENERALIZED HYPERMOBILITY addition to their ability to direct immune functions through T cell and NK cell receptor recognition, MHC-I are recognized by members of the Toby Smith1 1 leucocyte Ig-like receptor (LILR) family expressed on antigen-present- School of Rehabilitation Sciences, University of East Anglia, ing cells. Whilst T cell and NK cell receptors are finely tuned for self/ Norwich, UK non-self-discrimination, LILR have received relatively little attention in disease association studies owing to their broad specificity for multiple Background: Benign joint hypermobility syndrome (BJHS), which is alleles and forms of MHC-I. Recent studies have shown that MHC-I characterized by characterized by excessive joint and soft tissue, is specific LILR vary in the strength of their binding to different alleles and associated with a range of clinical symptoms including widespread to different forms of MHC, and that these variations have functional pain. In this talk, we will be exploring two specific areas of implications. For example, variations in LILRB2-binding strength for hypermobility presentation and management. Firstly, we will explore MHC-I have been shown to correlate with control of HIV1 infection. the extent to which the pain experienced by people with BJHS might These findings highlight a growing relevance for LILR in autoimmunity, be modulated by psychological symptoms including anxiety and where alterations in receptor and ligand expression have been depression. Secondly, physiotherapy and occupational therapy may observed for various conditions. LILR are powerful immune-regulators, be considered corner-stone treatments for this population. Therefore, with the ability to modulate both innate and adaptive functions of we will examine the literature to determine the efficacy and effective- leucocytes. Future studies will define the cell subsets and mechanisms ness of physiotherapy and occupational therapy interventions in the through which these receptors may influence the outcome of disease. treatment of people with symptomatic joint hypermobility. Disclosure statement: R.A. has received funding from the Cancer Methods: A systematic review of the published (AMED, CINAHL, Vaccine Institute and the Animal Health and Veterinary Laboratories Medline, Embase, PubMed, Cochrane Library) and unpublished Agency. research databases (OpenGrey, the WHO International Clinical Trials Registry Platform, Current Controlled Trials, the UK National Research I60. THE ROLE OF TOLL-LIKE RECEPTORS IN THE Register Archive) was undertaken. Case-control, cohort study design PATHOGENESIS OF RHEUMATOID ARTHRITIS and randomized and non-randomized controlled studies assessing the prevalence and incidence of psychological conditions, and the Sandra Sacre1 management of people diagnosed with BJHS were included. Meta- 1Trafford Centre for Medical Research, Brighton and Sussex Medical analysis assessing odds ratio (OR) and standardized mean difference School, Brighton, UK in severity of psychological conditions and treatment effect were performed. Methodological quality was assessed using the CASP RA is an autoimmune disease that primarily affects the joints. Peripheral appraisal tools. blood mononuclear cells migrate into the joint space, where alongside i12 Wednesday 29 April 2015 INVITED SPEAKER ABSTRACTS

other tissue resident cells such as synovial fibroblasts, they release pro- HIV is a global pandemic. Associated with opportunistic infections and inflammatory cytokines leading to pain and irreversible joint damage. malignancies, its untreated prognosis was poor. However, since the For several years, biologicals therapies targeting inflammatory cyto- advent of combination anti-retroviral therapies (ARTs), the prognosis kines and their receptors have been the focus of clinical treatment, has been dramatically transformed. This has led to a growing demonstrating the importance of TNF, IL-1 and IL-6 in RA pathology. population of people living with chronic HIV infection on long-term However, the receptors and signaling pathways underlying cytokine treatment. Several chronic metabolic complications have been production have remained unclear. A potential role for Toll-like observed (cardiovascular, diabetes, dementia, osteoporosis) and receptors (TLRs) in the pathogenesis of RA has been proposed by some of the ARTs have been implicated. Rheumatic manifestations many groups over the past decade. TLRs are key regulators of innate of HIV have been described since the late 1980s but have probably immunity that detect and respond to pathogens by up-regulating cell been altered by the use of combination ART. This talk will take a case- surface markers and inducing cytokine production. The concept that based approach to discuss issues in the diagnosis of rheumatic TLRs may be driving cytokine production in RA gained momentum after diseases among patients with HIV and remind the audience about the discovery that TLRs can recognize not only pathogens but also unusual (rheumatic) presentations of HIV-infected patients. Some endogenous molecules found at sites of inflammation and tissue interactions of rheumatic therapies with combination ART will be damage. As such, TLRs may have a role in perpetuating chronic presented. There is currently limited evidence about use of DMARDs inflammation in many autoimmune diseases in the absence of infection. and biologics in HIV-infected patients but this evidence will be A wealth of data has been produced from both murine and human tissue reviewed and a pragmatic approach to therapy discussed. models of RA. We have demonstrated TLR activity and a functional link Disclosure statement: The author has declared no conflicts of between TLR signaling, spontaneous cytokine production in human RA interest. synovial tissue and disease progression in murine arthritis models. These models revealed a potential contribution from a subset of the TLRs located in the endosomal compartment and in particular TLR8 I63. HEADACHE: GCA OR NOT GCA? appeared to be important in TNF production from human samples. Bhaskar Dasgupta1 Further examination of peripheral blood monocytes has revealed 1 upregulated expression of TLRs and TLR induced cytokine production Rheumatology, Southend University Hospital NHS Foundation in RA monocytes compared with healthy controls. In addition, Trust, Westcliff-on-Sea, UK dysregulation of downstream signalling regulators that are normally induced upon TLR activation to bring about tolerance may also be of GCA is a critically ischemic disease which can present with irreversible importance in these patients. sight loss in up to 20% of cases. This happens almost always before Disclosure statement: The author has declared no conflicts of interest. the start of glucocorticoid therapy. Fast track GCA pathways have shown that irreversible sight loss can be reduced significantly by early recognition, referral and treatment of GCA. Hence the accuracy of GCA diagnosis or its exclusion is paramount for improved outcomes and better management of GCA. This lecture will discuss the typical and atypical presentations of GCA and its common and uncommon mimics. The differential diagnosis of GCA includes other causes of ESSENTIALS IN RHEUMATOLOGY: headaches such as migraine, chronic headaches, causes related to ENT conditions, cervical spine causes as well as serious pathology CLINICAL KNOWLEDGE AND PRACTICE related to intra-cranial causes, neoplasia, infection, infiltrative dis- eases, cerebrovascular ischemia, other ocular causes of sight loss and other vasculitides. ‘Traffic signs’ that will help navigate towards or away from a GCA diagnosis with the required assessments and investigations will be discussed. Non-headache presentations of GCA I61. ACTIVE RA DESPITE DMARDS: WHERE NEXT? such as with polymyalgia and severe constitutional features (poly- Shouvik Dass1 myalgia arteritica) will also be discussed. Recent advances in imaging 1Department of Rheumatology, Leeds Teaching Hospitals NHS Trust, that have led to a better diagnosis of GCA and large vessel vasculitis Leeds, UK will also be mentioned. Disclosure statement: The author has declared no conflicts of interest. The treatment of RA continues to evolve rapidly. This provides opportunities and challenges for clinicians and patients. Biologic DMARDs (bDMARDs) have now become relatively commonplace, although there are still contentious areas and unanswered questions. Despite the fact that there are guidelines and pathways for treatment of RA in those patients in whom conventional DMARDs have been ineffective—based on measures of clinical efficacy and cost- DIAGNOSIS AND MANAGEMENT OF effectiveness—choosing and using biologic agents effectively may not COMMON SHOULDER PROBLEMS IN always be straightforward. Issues that may be left unaddressed by such guidelines include the optimal management of those patients PRIMARY CARE with active RA who may not qualify for funding for bDMARDs. Furthermore, there is now a drive to personalize care more effectively with increasing data informing approaches that target therapies more effectively in individual patients. The use of biomarkers and their role in I64. SHOULDER PAIN: THE DILEMMA OF DIAGNOSIS clinical practice is important here. This presentation will review the Karen Ginn1 evidence for and differences between anti-TNF agents as well as the 1 latest data for other targeted therapies e.g. B cell, IL-6 and School of Medical Sciences, Sydney Medical School, Sydney, costimulation agents. This will include an assessment of the latest Australia data regarding safety considerations, drawn from studies and registries. Beyond that, the recent introduction of small molecule The primary aim of a diagnostic classification system is to enhance therapies will also be reviewed. The upcoming introduction of treatment success by identifying subgroups within the overall popula- biosimilars and generic bDMARDs and their potential impact on tion of patients with a particular disorder, that differ with respect to clinical practice will also be considered. This session aims not only to their prognosis and the benefit that can be expected from treatment provide an overview of current guidance and the latest evidence base options. A secondary aim is to facilitate communication between for bDMARDs but also to equip the clinician with ways of using these health professionals and between health professional and patients. agents in the most effective way possible for patients. The current diagnostic classification system for shoulder pain Disclosure statement: S.D. has received honoraria from Roche and disorders fails to achieve either of these aims. There are no generally GSK. applied criteria for the various diagnostic labels for shoulder pain. Existing diagnostic categories overlap considerably and can be present concurrently. No wonder diagnostic agreement between I62. HIV AND RHEUMATIC DISEASES clinicians is little better than fair, even when clinicians examine patients together and discuss the signs and symptoms prior to Karen Walker-Bone1 recording separate diagnoses. Perhaps of more concern is the fact 1Southampton General Hospital, MRC Lifecourse Epidemiology Unit, that individual clinical trials evaluating the effectiveness of treatment University of Southampton, Southampton, UK for shoulder diagnostic subgroups, in which strict criteria were used to INVITED SPEAKER ABSTRACTS Wednesday 29 April 2015 i13

identify the particular subgroup under investigation, have not found commissioning. The Specialised Rheumatology CRG has been one of strong evidence to support the use of a particular treatment approach the most active groups, working to promote the role for patients with a particular diagnosis. The evidence would strongly of our specialty within NHS England and the needs of our patients. This indicate that the current diagnostic classification system for shoulder has led to the publication of several Comissioning Policies, the pain is of little benefit to patients suffering from shoulder pain. development of a Quality Dashboard, and a nationally supported QIPP Disclosure statement: The author has declared no conflicts of proposal to develop a coordinated network for specialized rheumatol- interest. ogy. This session will provide an opportunity to hear further updates about this work. Disclosure statement: P.L. is a member of the speakers’ bureau of I65. TREATING SHOULDER PAIN IN PRIMARY CARE: Pfizer (unconnected to SLE); and serves on the advisory board for STEROID INJECTIONS OR EXERCISES? Eli Lilly. Elaine M. Hay1 1 Research Institute for Primary Care and Health Sciences, Keele I69. THE ROLE OF NHS ENGLAND COMMISSIONING University, Keele, UK POLICIES IN PROMOTING EQUITABLE ACCESS TO HIGH- COST DRUGS Abstract not provided. Marina Anderson1 Disclosure statement: The author has declared no conflicts of 1 interest. Department of Rheumatology, University of Liverpool, Aintree University Hospital, Liverpool, UK

I66. WHEN PRIMARY CARE MANAGEMENT FAILS: WHAT National Health Service England (NHSE) has a remit to achieve equity ARE THE OPTIONS AND WHEN SHOULD I REFER? and excellence in the provision of specialized rheumatology care and treatment in England. In order to tackle local variations and raise Ron Dodenhoff1 national standards of care, the NHSE Specialised Rheumatology 1The Shrewsbury and Telford Hospital NHS Trust, Shrewsbury, UK Clinical Reference Group (CRG) has been established. This CRG comprises a chair, national clinical director co-chair, 14 regional Abstract not provided. clinical senate members, patient and carer members, affiliate Disclosure statement: Author has declared no conflict of interest. organization members, the lead NHSE commissioner, a lead and public health lead. The CRG’s task is to deliver the products of commissioning to be used by the 10 specialized services Area Teams to contract services. In order to achieve this, one of the key roles of the CRG is to develop commissioning policy documents that define access to particular services and therapies for specific cohort of SPECIALIZED SERVICES patients. One such recent NHSE Clinical Commissioning Policy sets out criteria for use of sildenafil and bosentan for the treatment of digital COMMISSIONING: WHAT’S IN IT FOR ulceration in systemic sclerosis. The development and resultant final RHEUMATOLOGY? content of this policy will be presented. Mechanisms for achieving national implementation of this policy will be discussed. Disclosure statement: M.A. has received honoraria from Actelion.

I67. THE ROLE OF NHS ENGLAND IN SPECIALIZED I70. THE EMERGING ROLE OF QUALITY DASHBOARDS; COMMISSIONING HOW DO WE DEMONSTRATE OUR COMPLIANCE AND CONTRIBUTION TO VALUE? Sarah Watson1 1 Specialised Commissioning, NHS, UK Bridget Griffiths1 1Freeman Hospital, Freeman Hospital, Newcastle upon Tyne, UK Abstract not provided. Disclosure statement: The author has declared no conflicts of Abstract not provided. interest. Disclosure statement: The author has declared no conflicts of interest. I68. THE ROLE OF THE NHS ENGLAND CLINICAL REFERENCE GROUP IN PROMOTING RHEUMATOLOGY AND THE NEEDS OF OUR PATIENTS Peter Lanyon1 1Nottingham University Hospital, Nottingham University Hospital, BRITS: ADOLESCENT RHEUMATOLOGY: Nottingham, UK WHAT RHEUMATOLOGY TRAINEES Changes to the UK National Health Service (NHS) following the Health NEED TO KNOW and Social Care Act 2012 have resulted in the majority of medical care being commissioned locally by Clinical Commissioning Groups (CCGs). However, for a small number of high-cost, low-volume services in every area of medical practice, NHS England has now I71. WHAT IS UNIQUE ABOUT ADOLESCENCE AND AN assumed national responsibility for the direct commissioning of this INTRODUCTION TO JIA specialized care. The ambition behind this change is to ensure that 1 people living with rare diseases, or rare manifestations of more John Ioannou 1 common diseases, achieve equity and excellence in the provision of Adolescent and Adult Rheumatology, University College London, their care, regardless of where they live. For Specialised London, UK Rheumatology, the service specification comprises severe manifesta- tions of autoimmune rheumatic disorders and vasculitis, inherited Abstract not provided. disorders of connective tissue and rare metabolic, sclerosing and Funding: This study was funded by Arthritis Research UK, Lupus UK dysplastic bone diseases. Clinical Reference Groups for each and Action Research. specialty were established in April 2013 as the primary source of Disclosure statement: J.I. has received consultancy fees from Pfizer clinical advice to NHS England to guide this transition to specialized and AbbVie. i14 Wednesday 29 April 2015 INVITED SPEAKER ABSTRACTS

I72. HOW TO CONDUCT A CLINICAL CONSULTATION FOR AN ADOLESCENT AND YOUNG ADULT AND WHAT DOES THIS CLINIC LOOK LIKE ESSENTIALS IN RHEUMATOLOGY: Rachel Tattersall1 UPDATE FROM THE EXPERTS 1Rheumatology, Sheffield Teaching Hospitals and Sheffield Children’s Hospital, Sheffield, UK

Abstract not provided. I76. THE ROLE OF ORTHOPAEDIC : Disclosure statement: R.T. has received speaker fees from Pfizer and CURRENT TRENDS AND DEVELOPMENTS AbbVie. Lindsay Muir1 1Department of Orthopaedics, Salford Royal NHS Foundation Trust, UK

This talk will cover current concepts in hand surgery in rheumatological conditions. This will include tendon disorders, joint replacement in the THE GUT MICROBIOME AND wrist, MCP and IP joints, current thoughts in the management of SSc, psoriasis and gout. INFLAMMATORY ARTHRITIS Disclosure statement: The author has declared no conflicts of interest.

I73. THE GUT MICROBIOME IN HEALTH AND DISEASE I77. THE ROLE OF MRI AND ULTRASOUND IN RHEUMATIC DISEASE 1 Karen Scott 1 1University of Aberdeen, Aberdeen, UK Charles Hutchinson 1Clinical Imaging, University of Warwick, Coventry, UK Abstract not provided. Abstract not provided. Disclosure statement: Disclosure statement: C.H. has received grant of £38 000 from GE Healthcare to investigate the use of US in the diagnosis of AAA. I74. THE ROLE OF THE GUT MICROBIOME IN AXIAL SPONDYLOARTHRITIS Simon Milling1 1Centre for Immunobiology, University of Glasgow, Glasgow, UK

Colonic inflammation can be detected in a large proportion of patients IMPROVING QUALITY OF LIFE FOR with SpA. Anecdotal reports and studies using animal models indicate OLDER ADULTS WITH that there may be a causal link between intestinal and systemic inflammatory symptoms. With the recent development of methods for MUSCULOSKELETAL CONDITIONS analysing the microbial communities to which we play host, and many emerging descriptions of mechanisms underlying our inter-reliance, many researchers are now investigating how changes in microbial communities may contribute to disease. I will introduce this field, I78. OLDER ADULTS WITH MUSCULOSKELETAL describe some key recent findings and discuss how changes in the CONDITIONS: CHALLENGES AND OPPORTUNITIES intestine might contribute to the development and maintenance of Ross Wilkie1 inflammation in axial spondyloarthritis. 1 Funding: This study was funded by Boehringer Ingelheim. Research Institute for Primary Care & Health Sciences, Keele Disclosure statement: The author has declared no conflicts of University, Keele, UK interest. Abstract not provided. Disclosure statement: The author has declared no conflicts of I75. THE ROLE OF THE GUT MICROBIOME IN THE interest. DIFFERENTIATION OF REGULATORY B CELLS IN ARTHRITIS Claudia Mauri1 1 I79. MANAGING COMORBIDITIES AND THE CHALLENGE OF Division of Medicine, University College London, London, UK POLYPHARMACY IN OLDER ADULTS WITH MUSCULOSKELETAL CONDITIONS IL-10 producing regulatory B cells (Bregs) play a critical role in the regulation of immune homeostasis. Whilst there has been intense Adrian Jones1 investigation into the effector function of Bregs, little is known about the 1Rheumatology, Nottingham University Hospitals NHS Trust, stimuli driving their differentiation. In this talk I will discuss data showing Nottingham, UK that gut microbiota drives the differentiation of T helper 1, 17 and other pro-inflammatory cytokines mediating the pathogenesis of arthritis. We Clinical training and randomized controlled trials have long addressed also report a paradoxical effect by which the same pro-inflammatory individual diseases in individual patients and their optimum manage- stimuli, induced by the gut microbiota, are perceived as dangerous ment. The increasing reality of clinical practice in all arenas is that most signals and they are pivotal for the activation and differentiation of fully of our patients have multiple morbidities and are on multiple functional Bregs. Indeed, mice treated with antibiotics exhibit not only a pharmacological agents. Results from clinical trials often mask this reduced arthritogenic response to antigen, but also a lack of complexity by filtering recruitment eligibility in terms of age (young and suppressive Bregs as shown by an inability to produce IL-10 or old), reproductive capability, comorbidity and comedication resulting suppress arthritis upon adoptive transfer. Furthermore, we have in conclusions that are really often only representative of the highly identified IL-1 beta and IL-6, which are produced in response to the selected study population. Particular issues arise with the elderly who induction of arthritis only in mice with a conventional microbiome, as are often specifically excluded from recruitment and/or may find trial master cytokines in the activation of IL-10 producing Bregs. Taken participation difficult. The reality in clinical practice is that the together, these results indicate that the host-symbiont relationship in population is ageing and often (but not inevitably) as part of that the gut is important, not only in inflammation and host defence, but also process an individual patient has acquired multiple morbidities and in the induction and function of Bregs. even more medications. Each speciality makes strong recommenda- Disclosure statement: The author has declared no conflicts of tions for their aspect of health often with little regard for these interest. complexities. For example, the recommendations for a patient with INVITED SPEAKER ABSTRACTS Wednesday 29 April 2015 i15

diabetes might include three to four drugs for glycaemic control, changed, many challenges remain. Over 30 years ago, RA was two to three drugs for hypertension, two for their vascular disease managed differently. Initial treatment focussed on symptom control and two to three eye drops—and then the patient develops mainly using non-steroidal anti-inflammatory drugs. Second-line drugs arthritis. Not surprisingly, this complexity results in issues for all such as gold injections and steroids were delayed until symptomatic parties. The clinician is faced with a host of potentially interacting treatments failed. Disease assessments were not standardized. Many drugs whose synergies and antagonisms may be hard to predict and different assessments were used with clinicians varying in what they often over- or under-stated. The patient is faced with a diet of pills recorded. Clinical trials were usually short-term and were often small whose cost both financial and in terms of inconvenience may and underpowered. These approaches achieved medium-term bene- adversely affect concordance. The prescriber and dispenser is faced fits. However, patients showed substantial short-term erosive pro- with an ever increasingly complex drug list whose breadth and gression and poor long-term clinical outcomes. After 20 years of completeness can be hard to define; particularly when multiple specialist management, about half of our patients were dead or prescribers are involved. The health economy is faced with an severely dizabled. After 30 years of innovations, there have been increasing drug cost in terms of prescribed drugs, drug wastage and substantial and sustained improvements in managing RA. These span the cost of treating drug interactions. In this talk I will describe this three themes: better outcome assessments; more effective treat- problem using illustrative cases to highlight the issue. I will also ments; and greater standardization in the delivery of care. Better suggest pragmatic ways that we might approach the problem and outcome assessments: clinical assessments have been rationalized. some principles that might be employed to rationalize medication lists An internationally accepted core set of outcome measures has been and to concentrate on the most important morbidities. I will also developed. Combining these core measures reproducibly defines discuss end of life care and planning for those patients with life-limiting overall therapeutic benefits. As a result it is easier to identify effective illnesses. new treatments and to monitor patients in routine clinical practice. Disclosure statement: The author has declared no conflicts of However, current assessments are not ideal: they underestimate interest. factors of critical importance to patients, like pain and psychological impacts; they overemphasize laboratory tests like elevated erythrocyte sedimentation rates. More effective treatment: therapy is far better. I80. ENGAGING WITH OLDER PEOPLE TO DEVELOP AND Established disease modifying drugs are used more effectively, DELIVER INTERVENTIONS FOR SELF-MANAGEMENT OF particularly when starting intensive treatment regimens in early CHRONIC MUSCULOSKELETAL CONDITIONS disease. Novel biologic treatments have been developed, ranging Denis Martin1 from tumour necrosis factor inhibitors and cytokine inhibitors to agents 1School of Health & Social Care, Teesside University, affecting T and B cells. We are starting to value and use non-drug Middlesborough, UK treatments like exercise. However, there are many outstanding challenges. Current treatment strategies are not universally effective Abstract not provided. and only a minority of patents achieve remissions. There are Disclosure statement: The author has declared no conflicts of uncertainties about the merits of different intensive treatment interest. strategies. Not all patients require identical therapy and approaches may be needed; for example intensive treatment in early disease only increases remissions in anti-citrullinated peptide antibody-positive patients. Innovations in care delivery: guidelines and standards of care have ensured new approaches are implemented in routine practice. Consultant numbers have doubled, increasing access HEBERDEN ORATION to expert care. Consequently, fewer patients have active RA, more have remissions and outcomes are better. However, we need to take more account of patients’ perspectives when planning care. Integrating basic science, clinical and health services research has I81. CHANGING THE COURSE OF RHEUMATOID ARTHRITIS driven substantial long-term improvements. Each innovation has only small effects but their combined impact has been transformative. David L. Scott1 However, it is crucial for rheumatology to maintain its research 1Rheumatology, King’s College London, London, UK momentum while RA still remains an unresolved major clinical problem. Three decades of advances in assessing and managing RA have Disclosure statement: The author has declared no conflicts of transformed its course and improved its outcome. Although much has interest. i16 Thursday 30 April 2015 INVITED SPEAKER ABSTRACTS

recommended use of ULT in people with gout in the UK is worse than suboptimal. There is a clear educational requirement to improve PHARMACOEPIDEMIOLOGY: NEW knowledge and interest of health professionals in the management of TRUTHS, NEW LIES gout and to include patients in decision-making. Disclosure statement: M.D. has served on ad hoc advisory boards on gout or OA for AstraZeneca, Menarini, Nordic Biosciences, Novartis and Pfizer. I82. ADVERSE EFFECT OF STATIN USE IN POPULATION STUDIES I84. STEROID SAFETY: WHAT WE KNOW, WHAT WE DON’T Tjeerd-Pieter van Staa1 KNOW AND WHY 1 Health eResearch Centre, University of Manchester, Manchester, UK Will G. Dixon1 1ARUK Centre for Epidemiology, Centre for Musculoskeletal Statins are widely used for the prevention of cardiovascular disease Research, Manchester Academic Health Science Centre, University (CVD). They have been evaluated in a large number of blinded, of Manchester, Manchester, UK randomized trials. Despite this large evidence base, there are still areas of considerable disagreement. Currently, risk scores such as This presentation will review what is known and what is not known QRISK2 and Framingham are used to select patients for primary about the safety of steroids in inflammatory musculoskeletal disease. It prevention treatment. However, recent research has found that these will include some of the methodological challenges in addressing this risk scores predict low risk well but high risk poorly. Recent guidelines important but challenging question. in the UK advocate prescribing statins to patients with a 10-year CVD Disclosure statement: W.G.D. has received research support from risk of 10%. But is this a sensible approach given lifetime adherence to the MRC. treatment by patients does not occur? There is also uncertainty about the risks of side effects with statins: the blinded trials reported no increase in muscle pain risk, while there are frequent observations of muscle pain side effects in routine clinical practice. This presentation will propose possible approaches to resolve these uncertainties, including large simple trials using routinely collected data and genetic research on predictors of side effects. HOW TO WRITE, REVIEW AND EDIT FOR Disclosure statement: The author has participated in advisory RHEUMATOLOGY JOURNALS meetings with GSK and Boehringer and provided methodological advice to Laser (not related to statins).

I83. POPULATION USE OF URATE-LOWERING THERAPY I85. UPGRADING STANDARDS OF ETHICAL PUBLISHING IN RHEUMATOLOGY JOURNALS Michael Doherty1 1Academic Rheumatology, Nottingham University, Nottingham, UK Armen Gasparyan1 1Departments of Rheumatology and Research & Development, Gout is the most common inflammatory arthritis worldwide. The total Russell’s Hall Hospital, Dudley Group NHS Foundation Trust, population prevalence of gout in the UK was 2.5% in 2012, a 64% Teaching Trust of University of Birmingham, Dudley, UK increase from the 1.4% prevalence in 1997. However, urate-lowering therapy (ULT) can cure gout by maintaining serum uric acid (SUA) Aim: To analyse the current state of ethical standards of publishing in levels below the saturation point for urate crystal formation, thus indexed rheumatology journals and suggest ways to upgrade them. eliminating the pathogenic agents (urate crystals) that cause gout, and Methods: Searches through the PubMed and SCImago Journal & reducing health risks associated with high urate levels (e.g. cardio- Country Rank platforms and the Instructions for Authors of indexed vascular disease, stroke, chronic kidney disease). ULT is inevitably rheumatology journals were conducted to retrieve data on duplicate required to achieve cure even if modifiable risk factors are addressed and retracted publications, scientific authorship, transparency of peer by lifestyle and other changes. Although some believe that ULT should review, and competing interests disclosures. Impact indicators of the be considered and discussed with everyone with gout, current BSR, indexed rheumatology journals were retrieved from Web of Science EULAR and ACR guidelines at least concur in recommending ULT for and SCImago Journal & Country Rank. people with more severe gout (e.g. tophi, joint damage) or concomitant Results: Quantitative records of duplicate and retracted items of conditions (e.g. urolithiasis, diuretic therapy). So how well managed thirty-seven rheumatology journals visible in PubMed and listed in are people with gout in the UK? Using data from the Clinical Practice SCImago database were analysed. Six items were tagged as Research Datalink, prescribing patterns for ULT have remained duplicates. Two identical meta-analyses from South Korea were essentially unchanged from 1997, with only 38% of people with gout published in the same issue of Rheumatology International in 2006, ever receiving ULT. However, even at first presentation fully 44% of possibly due to production mistakes. Two overlapping practice incident gout patients appear eligible for ULT according to current guidelines in Croatian were published in Reumatizam in 2007 and guideline criteria, and within 5 years 87% become eligible. Individual 2008. Twenty-two retracted articles were found across rheumatology practice prescribing of ULT varies from 0% to 100% and examination journals. Reasons for retractions ranged from plagiarism to lack of of patient- and practice-level factors accounts for only 8% and 13% of institutional ethics approval. We scanned online instructions of 44 total prescription variance, respectively, suggesting that ULT prescrib- rheumatology journals and found that statements on authorship were ing follows no clear logic and is almost random. Furthermore, present in only 13 (29.5%). A specific reference to the renewed four allopurinol is the main ULT used but the majority of prescriptions are criteria of authorship by the International Committee of Medical for <300 mg/day and doses above 300 mg/day are rare (2% of Journal Editors was present in only 8 (18.2%) instructions. Peer-review prescriptions), even though the current median dose to achieve the models and number of external reviewers were mentioned in only 10 minimum therapeutic target (<360 mmol/l) in community-based (22.7%) and 11 (25%) journals, respectively. It was also noted that only patients is 400mg/day. Very few general practitioners (<1%) undertake seven (16.3%) rheumatology journals adopted comprehensive policies repeat SUA tests, implying that the concept of targeting ULT dose on competing interests disclosures for authors, reviewers and editors. against a specific SUA target is largely absent. Adherence to ULT Conclusion: Our series of searches through bibliographic databases overall is low, but has improved from 28.28% (95% CI 27.33%, and platforms indexing rheumatology journals suggest that more 29.26%) in 1997 to 39.66% (95% CI 39.11%, 40.22%) in 2012. The efforts are required to implement self-correction and upgrade ethical main barrier to care of people with gout appears to be knowledge of statements in the instructions for authors. The role of editorial gout amongst health professionals. When patients are fully informed associations and their guidelines on ethical research reporting and about gout, its outcomes and the treatment options, 100% want to publishing can be instrumental in improving the quality and ethical receive ULT and adherence is excellent, with more than 9 out of 10 values in rheumatology journals. patients achieving the therapeutic target at 1 year. In conclusion Disclosure statement: The author has declared no conflicts of interest. INVITED SPEAKER ABSTRACTS Thursday 30 April 2015 i17

I86. IMPACT INDICATORS OF RHEUMATOLOGY JOURNALS Musculoskeletal disease constitutes a major health burden worldwide. Robert Moots1 The principal chronic musculoskeletal disorders are osteoporosis, 1Department of Musculoskeletal Biology, University of Liverpool, sarcopenia and OA; these conditions increase in frequency with Liverpool, UK advancing age, and understanding their epidemiology throughout the life course is critical to the development of effective preventive Abstract not provided. strategies. Osteoporosis contributes to disability and death through its Disclosure statement: The author has declared no conflicts of association with age related fractures. These fractures typically occur interest. at the hip, spine and distal forearm. It has been estimated from incidence rates derived in North America that the lifetime risk of a hip fracture in Caucasian women is 17.5% with a comparable risk in men I87. WRITING A PAPER FOR RHEUMATOLOGY of 6%. Sarcopenia refers to an age related loss of skeletal muscle Jaap van Laar1 mass and function. Between the ages of 20 and 80 years, a decline in 1Department of Rheumatology & Clinical Immunology, University muscle fibre size and number causes a loss of muscle mass (30%), with a greater accompanying loss of muscle strength (60%). The Medical Centre Utrecht, Utrecht, The Netherlands origins of sarcopenia are multifactorial and include biological senes- cence, muscle disuse, endocrine dysfunction, comorbidity, inflamma- Abstract not provided. tion and nutritional deficiency. While the clinical relevance of Disclosure statement: The author has declared no conflicts of sarcopenia is widely recognized, there remains no universally interest. accepted definition of the term. Recent approaches to definition incorporate combinations of decline in fat free mass by DXA; strength assessments using isometric dynamometry; and poor physical performance using observational tests (gait speed, sit to stand time and standing balance). The establishment of these recent methods for the assessment of sarcopenia has led to a characterization of the AGEING WELL: IS IT ABOUT BONE OR prevalence of this disorder with advancing age in men and women. MUSCLE OR BOTH? Modifications of the definition will inform outcome studies and future randomized controlled trials. Finally, shared aetiological mechanisms underpinning the senescence of bone, muscle and joint, will open an arena in which novel therapeutic strategies for musculoskeletal disease will become available. I88. BIOLOGY OF AGEING APPLIED TO BONE AND MUSCLE Disclosure statement: C.C. has received consultancy honoraria from Steve R. Cummings1 Servier, Merck, Amgen, Novartis and Eli Lilly; and has received 1San Francisco Coordinating Center, California Pacific Medical honoraria from Servier, Merck, Amgen, Roche, Novartis, Eli Lilly and Center Research Institute, San Francisco, CA, USA Medtronics.

Like any structure, bone and muscle undergo cycles of damage and I90. NOVEL THERAPEUTIC TARGETS WITH POTENTIAL TO repair, and when accumulation of damage exceeds the rate of repair, INFLUENCE BONE/MUSCLE the system fails. Bridges collapse, aeroplanes break and older adults fall and fracture a hip. To understand ageing, it is useful to consider Rene Rizzoli1 two types of cell: those that continue to reproduce, like osteoblasts 1HUG/Specialites de Medicine, University of Geneva, Geneva, and muscle stem cells, and terminally differentiated cells that live a Switzerland long time, such as osteocytes. Short-lived cells, such as precursors to osteoblasts, undergo senescence, perhaps due in part to short- The prevention of fragility fracture relies on the triad of balanced ening of telomeres. Senescent cells produce mediators of inflamma- nutrition, including calcium, protein and vitamin D; physical exercise; tion, such as IL-6. Preserving telomeres increases osteoblast function and pharmacological therapies. The goals of these measures are to in vivo and may maintain bone formation that otherwise declines with modify the two main components of fracture risk, which are ageing. Terminally differentiated cells accumulate damage, mainly mechanical overload, i.e. falls, and mechanical incompetence, i.e. oxidative damage due to the production of reactive oxygen species bone fragility. For the latter, new regimens are in development aimed (ROS) by the process of oxidative phosphorylation to generate at increasing bone mass and particularly bone strength, by influencing adenosine triphosphate (ATP). Autophagy recycles the products of cellular and biochemical pathways not targeted by available anti- intracellular damage. Blocking autophagy in murine osteocytes osteoporosis agents. For instance, to transmit to the osteoblast signals replicates osteoporosis and, in muscle, leads to many features of of mechanical loading or parathyroid hormone, osteocytes are using aged muscle. All of these processes require energy and 90% of the the WNT/beta-catenin pathway. This pathway is becoming the target ATP produced by mitochondria, which diminish in mass and function of pharmacological intervention to decrease the expression of with ageing. Maintaining the amount and function of mitochondria in negative regulators of bone formation like sclerostin. Phase III trials, the skeletal muscle of mice prevents many features of ageing: it monoclonal antibodies against sclerostin, tested either against preserves bone mass and treadmill performance, and extends the placebo, or alendronate, over 1 year, followed by denosumab, are lifespan of mice. These systems interact. Autophagy declines with ongoing. Odanacatib is a selective inhibitor of cathepsin K, which was ageing, leading to the accumulation of damaged molecules and tested in a 2-year phase IIb dose-ranging study given once weekly or mitochondria. Damaged and dysfunctional mitochondria accumulate placebo, and in extensions. Continuous treatment up to 8 years and produce more ROS and less ATP. This leads to a vicious cycle of resulted in further gains in BMD. Bone-resorption markers remained cell death and decreased function of muscle and bone that is reduced, while there was no significant change in bone-formation predicted to lead to an exponential increase in systems failure and markers. The results from a phase III trials have demonstrated a death with ageing. Many drug treatments are under development to consistent antifracture efficacy on vertebral and non-vertebral, includ- slow the rate of ageing and extend healthy life. The most effective ing hip fractures. Other agents targeting these pathways are under strategy remains exercise. This stimulates autophagy and mitochon- development. Combined and/or sequential therapies with available drial biogenesis and, in observational studies, reduces fractures, agents are further considered. For the age-related reduction in muscle mobility disability and in randomized trials significantly reduces mass and performance, characterizing sarcopenia, various agents mortality in older adults. affecting the myostatin activin receptor system are under clinical Disclosure statement: The author has declared no conflicts of development. In a phase II trial, monoclonal anti-myostatin antibodies interest. were shown to increase appendicular lean mass and muscle power, as assessed by a stair climbing test. Interestingly, pathways such as muscle derived IGF-I during muscle contraction, or myostatin are I89. CONTRASTING DEFINITIONAL APPROACHES TO capable of influencing bone turnover as well. SARCOPENIA AND OSTEOPOROSIS Disclosure statement: R.R. has received speaker or advisory board Cyrus Cooper1 fees from Amgen, MSD, GSK, Servier, Danone and Takeda for 1MRC Lifecourse Epidemiology Unit, University of Southampton, delivering lectures. Southampton, UK i18 Thursday 30 April 2015 INVITED SPEAKER ABSTRACTS

ADOLESCENT AND YOUNG ADULT HOW CAN WE ENCOURAGE PATIENT RHEUMATOLOGY PARTICIPATION IN THE CLINIC?

I91. YOUNG ADULT RHEUMATOLOGY SERVICE: WHAT IS IT, I94. INCREASING PATIENT PARTICIPATION IN NURSE-LED WHY DO WE NEED IT AND HOW TO COMMISSION FOR IT? RHEUMATOLOGY CLINICS: RESULTS FROM A MULTICENTRE OBSERVATION AND INTERVIEW STUDY Rachel Tattersall1 1Rheumatology, Sheffield Teaching Hospitals and Sheffield Jill Firth1 Children’s Hospital, Sheffield, UK 1Pennine Musculoskeletal Partnership, Oldham, UK

Young adults are those aged 16–25 years and are cared for in both Abstract not provided. paediatric and adult services: children with rheumatic disease Disclosure statement: J.F. has received a grant award from the Bupa transition into adult services, whilst many young adults’ first Foundation. experience of health services is in an adult setting. Young adults are in a unique period of development spanning adolescence (ages 10–19 years) and young adulthood (ages 20–25 years). This tumultuous, fast- I95. PATIENT ACTIVATION AND SELF-MANAGEMENT: paced time has well-recognized physical, hormonal and behavioural WHAT HAPPENS IN CLINIC? features but the importance of neurocognitive development is now Emma Dures1 increasingly recognized as young peoples’ brains continue to develop 1Academic Rheumatology, University of the West of England, Bristol, well into their mid-twenties. Transition is a well-characterized, active UK and planned process through which young people move into adult services. Key in the current evidence base for good transition is the Abstract not provided. concept of age and developmentally appropriate care for adolescents Disclosure statement: The author has declared no conflicts of and young adults (AYA). Evidence is accumulating that age and interest. developmentally appropriate care for AYA is best provided in age- banded clinics and for those over 16 in young adult clinics rather than general adult (or paediatric) services. This talk will argue that young I96. INNOVATE TO MOTIVATE: USING TELEHEALTH TO adult rheumatology services, aimed at the 16–25 year age group, FACILITATE ENGAGEMENT WITH PHYSICAL ACTIVITY provide AYA in adult rheumatology with best possible care and are Nicola Walsh1 resource neutral. It will discuss the practical approach to young adult 1Faculty of Health and Applied Sciences, University of the West of clinics and specifically address barriers in setting up these services. England, Bristol, UK Two crucial barriers are the difference in the specialized commission- ing of children’s’ rheumatology services compared with general Abstract not provided. commissioning of adult services and the continual shifting of the commissioning landscape. These differences often render AYA Disclosure statement: The author has declared no conflicts of invisible and ill served, and this talk will provide clinicians with interest. practical tools with which to address commissioning in this context. Disclosure statement: R.T. has received honoraria for talks from Pfizer and AbbVie.

I92. JUVENILE ONSET DERMATOMYOSITIS: CURRENT RHEUMATIC DISEASE AND THE KIDNEY STATE OF PLAY WITH BEST PRACTICE, EMERGING BIOMARKERS AND OUTCOMES Lucy Wedderburn1 1Rheumatology, University College London, London, UK I97. MANAGING LUPUS NEPHRITIS IN THE ERA OF BIOLOGIC THERAPIES JDM is a severe autoimmune disease of children and young people, 1 Elizabeth Lightstone causing skin rashes, severe muscle weakness and in some cases 1Section of Renal Medicine, Department of Medicine, Imperial attacking major organs (gut, lungs, brain), which can be fatal. JDM is College London, London, UK heterogeneous, both in clinical features and outcomes, with some patients achieving remission and others remaining highly resistant to Abstract not provided. treatment. In this talk we will review evidence that clinical ndo- Disclosure statement: phenotypes of JDM exist, in which particular complications are more E.L. has received research funding from likely. The myositis-specific autoantibodies (MSAs) in JDM are useful Roche; has acted as a consultant/advisor for Anthera, Aspreva biomarkers to identify these endo-phenotypes. For example, the MSA Pharmaceuticals, Biogen Idec, EMD Serono, Genentech, anti-MDA5 is associated with mild myositis, yet more severe skin GlaxoSmithKline, Medimmue, Merck, Roche, Teva, UCB and Vifor; disease, ulceration and interstitial lung disease. In contrast anti-NXP-2 and has received travel grants from GlaxoSmithKline, Roche and UCB. antibody is associated with calcinosis. We will review data relating to these different subtypes of disease, the pathological and immunolo- I98. MODERN STRATEGIES FOR THE MANAGEMENT OF gical mechanisms that underlie these specific phenotypes and how RENAL VASCULITIS they may translate to clinical practice. Lars P. Erwig1 Disclosure statement: The author has declared no conflicts of 1 interest. Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK Abstract not provided. I93. OPTIMAL MODELS FOR MANAGING CHRONIC Disclosure statement: The author has declared no conflicts of WIDESPREAD PAIN IN ADOLESCENTS interest. Jacqui Clinch1 1 Rheumatology, University Hospitals Bristol, Bristol, UK I99. RHEUMATIC DRUG PRESCRIBING AND THE KIDNEY

1 Abstract not provided. Mark Little 1 Disclosure statement: , Trinity College Dublin, Dublin, Ireland Abstract not provided. Disclosure statement: The author has declared no conflicts of interest. INVITED SPEAKER ABSTRACTS Thursday 30 April 2015 i19

Abstract not provided. BRITS: SERONEGATIVE ARTHRITIDES: Disclosure statement: Consultancy fees from Actelion, GSK, Takeda TEST YOUR KNOWLEDGE! and grant/research support from CSL Behring, Actelion, Novartis.

I104. ANKYLOSING SPONDYLITIS AND BIOLOGICS Karl Gaffney1 I100. EXPLORING HORIZONS IN AXIAL 1Department of Rheumatology, Norfolk and Norwich University SPONDYLOARTHRITIS Hospitals NHS Foundation Trust, Norwich, UK Karl Gaffney1 1Rheumatology, Norfolk and Norwich University Hospitals NHS Abstract not provided. Foundation Trust, Norwich, UK Disclosure statement: The author has declared no conflicts of interest. During the past decade there have been significant advances in our understanding and management of AS which has led to a dramatic improvement in patient outcomes. These advances include adoption of the term axial spondyloarthritis to encapsulate the whole range of disease, the potential for earlier diagnosis delivered by MRI, a focus on specialized multidisciplinary services and the availability of biologic therapies. Despite these advances, there are a number of key barriers DROITWICH MEDICAL TRUST LECTURE to better patient care including delay in diagnosis, incorrect diagnosis, variable access to specialist care and appropriate therapy and a paucity of prognostic markers and biomarkers. A number of new therapies are in the pipeline such that the therapeutic options are I105. DROITWICH LECTURE: A JOURNEY OF DISCOVERY IN expanding for this once forgotten and neglected condition. A CHANGING LANDSCAPE: THE EXPERIENCE OF A Disclosure statement: The author has declared no conflicts of interest. RHEUMATOLOGY NURSE Susan Oliver1 I101. JUST WHEN YOU THOUGHT PSORIATIC ARTHRITIS 1European League Against Rheumatism, University of Exeter, UK WAS EASY In the last decade, I have been fortunate enough to have worked with a Helena Marzo-Ortega1 wide range of organizations involved in the provision of healthcare 1Division of Rheumatic and Musculoskeletal Disease, Leeds within the UK and internationally. These include patient and profes- Musculoskeletal and Biomedical Research Unit, Leeds, UK sional organizations, policy makers, non-governmental quangos, charity-funded think tanks, pharmaceutical companies and many PsA is a chronic inflammatory condition that can occur in up to 30% of established, as well as newly commissioned, specialist services. Each individuals with skin psoriasis (Pso). Both PsA and Pso are polygenic experience has helped to build my understanding of the complexity of diseases with heterogenEous clinical phenotypes. Although tradition- the challenges we face in delivering high quality care in a cost effective ally thought to be more benign than RA, PsA is a severe disease with a way within the constraints of a National Health Service (NHS). substantial proportion of patients having established erosions by the Government policy, fiscal pressures and the needs for greater time they present to secondary care. Mostly, Pso predates the transparency in the cost effectiveness of care all put the NHS under development of the arthritis by many years. Recent imaging studies increasing pressure to change. Practitioners working at the coalface of have shown that PsA may be underdiagnosed in Pso patients by 30– the NHS know they will experience frequent demands for changes in 40%, suggesting than Pso may be more than skin deep. Further and their services. Change is fascinating but not always for those most intriguing is the association of Pso and PsA with metabolic experiencing the constant demands to re-design their services. How morbidity, which leads to a high risk of cardiovascular disease in some do some organizations implement change effectively whilst others of these patients, and is likely based on a complex interaction between flounder? Is the culture within an organization as important as the environmental and genetic factors. This adds considerably to the strategy? This lecture will explore key aspects of teamwork, innovation burden of disease which is compounded by significant psychosocial and leadership and consider how to make small steps to achieve morbidity. Although biologic therapies have had a significant impact on significant change. The big question is whether we can we survive the treatment and understanding of psoriatic disease, patients would frequent demands for re-design and yet feel empowered to offer a like a holistic approach to their disease management based on quality of care that continues to improve patient outcomes and offers collaborative work between specialties. us a sense of professional pride. Funding: H.M.-O. has received honoraria and/or grants from AbbVie, Disclosure statement: S.O. has received consultancy and honoraria Celgene, Janssen, MSD, Novartis, Pfizer and UCB to support the from AbbVie, MSD, Regeneron Pharmacueticals and Pfizer over the study described in the abstract. last two years. Disclosure statement: The author has declared no conflicts of interest.

OPPORTUNISTIC INFECTIONS BSR CLINICAL GUIDELINES

I106. VACCINATION IN RHEUMATOLOGY PRACTICE I102. PRESCRIBING IN PREGNANCY FOR RHEUMATOLOGY Jaap van Laar1 Ian Giles1 1Rheumatology & Clinical Immunology, University Medical Center 1Department of Rheumatology, University College Hospital, London, Utrecht, Utrecht, The Netherlands UK Abstract not provided. Abstract not provided. Disclosure statement: The author has declared no conflicts of Disclosure statement: The author has declared no conflicts of interest. interest. I107. AN EVIDENCE-BASED APPROACH TO PREVENTING I103. SCLERODERMA MANAGEMENT INFECTION IN THE THERAPEUTICALLY IMMUNOCOMPROMISED Christopher P. Denton1 1Department of Rheumatology, University College Hospital, London, Andrew Berrington1 UK 1Microbiology, City Hospitals Sunderland, Sunderland, UK i20 Thursday 30 April 2015 INVITED SPEAKER ABSTRACTS

There is no doubt that anti-rheumatic drugs, particularly the newer biologic agents, carry infective risks. However, the absolute risks THE CHALLENGE OF PUBLIC remain small and there are various strategies that might be expected to reduce them still further. Antimicrobial prophylaxis is probably not EDUCATION IN RHEUMATOLOGY one of them! Disclosure statement: The author has declared no conflicts of interest. I111. EDUCATING THE PUBLIC ABOUT ARTHRITIS I108. LATENT TUBERCULOSIS: MYTH OR REALITY? Benjamin Ellis1 1 1 Imperial College Healthcare NHS Trust, Arthritis Research UK, Muddassir M. Shaikh London, UK 1Rheumatology, Freeman Hospital, Newcastle upon Tyne, UK Improvements in population musculoskeletal health will require an Biological agents can be highly efficacious in the treatment of increase in the public’s understanding of arthritis. Better under- various inflammatory rheumatic diseases; however, their use is standing should help reduce delays to diagnosis, improve people’s associated with an increased risk of developing active tuberculosis ability to manage their own symptoms and support adequate and (TB). The talk will focus on latent TB in the context of effective allocation of health and care resources. This talk will review immunosuppression caused by biological agents. The presentation these potential benefits, and explore how this public need for will discuss the pathology and epidemiology of latent TB. I will also information can be met. describe the prevalence and risk of developing active tuberculosis in Disclosure statement: The author has declared no conflicts of those with latent TB. Different screening algorithms and tests will be interest. examined. Finally evidence behind screening and chemoprophylaxis will be presented. Disclosure statement: The author has declared no conflicts of I112. EDUCATING THE PUBLIC ABOUT RHEUMATOLOGY interest. AND THE SIMPLE TASKS CAMPAIGN Simon Bowman1 1Rheumatology, Selly Oak Hospital, Birmingham, UK

Abstract not provided. Disclosure statement: The author has declared no conflicts of BRITS: DERMATOLOGICAL interest. MANIFESTATIONS OF RHEUMATIC I113. INCREASING PUBLIC AWARENESS OF A CINDERELLA DISEASE: ALL YOU NEED TO KNOW DISEASE: LESSONS FROM THE FAST CAMPAIGN Gary Ford1 1Oxford University Hospitals NHS Trust, Oxford Academic Health I109. FOR RHEUMATOLOGISTS Science Network, Oxford, UK

1 Portia Goldsmith Abstract not provided. 1 NHS Dermatology Department, The Royal London & Homerton NHS Disclosure statement: G.F. is a member of speakers’ bureau for Trusts, London, UK Boehringer Ingelheim and Lundbeck; and has received honoraria from Cerevast for trial committee DMC work. Skin problems are common. This talk will attempt to provide an approach to managing rheumatology patients with skin problems. Some skin problems are manifestations of underlying Rheumatology disease, others are complications arising from treatment and many are just incidental. This talk will be largely clinical. The history and clinical signs which help in diagnosis will be discussed. The use and technique of skin biopsy will be covered and treatment will also be discussed. GET FIRED UP FOR AUDIT AND Finally, there will be discussion of the increased risk of cutaneous RESEARCH malignancies in Rheumatology patients on immunosuppressant therapies. Disclosure statement: The author has declared no conflicts of interest. I114. AUDIT AND RESEARCH: OVERCOMING THE BARRIERS Sandra M. Robinson1 I110. DERMATOLOGICAL MANIFESTATIONS OF 1Research and Development, Northumbria Healthcare NHS founda- RHEUMATIC DISEASE tion Trust, North Shields, UK David D’Cruz1 1Louise Coote Lupus Unit, St Thomas’ Hospital, London, UK To many nurses and allied health professionals (AHPs), audit and research appears to be undoable for multiple reasons. The aim of this Cutaneous lesions are a common and often typical presenting feature session is to address the issues that may hold back nurses and AHPs of autoimmune rheumatic disorders. SLE, the systemic vasculitides from doing audits and research. To dispel the myths that these are including ANCA-associated vasculitides and APS frequently present complicated processes which require special skills and to promote with cutaneous manifestations. However, early in the disease course, audit and research as tools which can provide the evidence they need skin lesions may be non-specific and a careful clinical history and to support their own roles in this changing National Health Service detailed examination supplemented by investigations including skin environment. biopsy will usually lead to an accurate diagnosis. The differential Disclosure statement: The author has declared no conflicts of diagnosis may include drug-induced skin reactions so a careful interest. medication history is essential. Examples include drug-induced vasculitis, proton pump inhibitor-induced flares of subacute cutaneous I115. MAKING THE MOST OF THE NIHR RESEARCH lupus and drug-induced lupus syndromes, for example, with long-term OPPORTUNITIES FOR HEALTH PROFESSIONALS minocycline use. It is also essential to consider alternative diagnoses that may mimic autoimmune diseases such as Jessner’s lymphocytic Anne-Maree Keenan1 infiltrate, which may be confused with cutaneous lupus. 1Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Multidisciplinary clinics with dermatologists may be helpful in facilitat- Hospital, Leeds, UK ing early diagnosis and treatment and are a useful educational and training opportunity. Abstract not provided. Disclosure statement: D.D.’C. has served as a consultant for GSK, Disclosure statement: The author has declared no conflicts of Roche, Aspreva, Human Genome Sciences and Eli Lilly. interest. INVITED SPEAKER ABSTRACTS Thursday 30 April 2015 i21

I116. A BEGINNER’S GUIDE TO PUBLISHING RESEARCH OR section advice focuses on screening and assessment before AUDIT treatment and patient education as well as safety aspects of monitoring. Topics also include suitability, eligibility, contraindica- Sarah Ryan1 1 tions, infection, vaccination, patient advice, monitoring, adverse Rheumatology, Haywood Hospital, Stoke-on-Trent, UK events, surgery and switching. The second subheading describes the administration of drugs and advice regarding home administra- Abstract not provided. tion, training, infusion reactions and treatment withdrawal. In the Disclosure statement: The author has declared no conflicts of children’s sections in addition to the assessment screening safety interest. and administration advice there is additional guidance on the use of licensed and non-licensed products and the specific needs of children and young people, including follow-up care and transition. There are several useful appendices and useful signposting through- out the document to current resources. This guideline provides practitioners with practical information to help them care for patients who require biologic therapies with different forms of inflammatory FROM TNF INHIBITION TO BIOSIMILARS: arthritis, in all care settings and provides a framework for best MANAGING SAFETY AND QUALITY practice. Disclosure statement: Honoraria: Napp advisory board and AbbVie nurse forum meeting.

I117. PRACTICAL MANAGEMENT OF PATIENTS ON I118. BIOSIMILARS: OUT OF THE LABORATORY AND INTO BIOLOGIC THERAPIES (UPDATED RCN AND BSR GUIDANCE) PRACTICE 1 Diana Finney 1 1 James Galloway Royal College of Nursing Rheumatology Forum, Royal College of 1 Rheumatology, King’s College London, London, UK Nursing, Brighton, UK In October 2013, the European Medicines Agency (EMA) approved Significant developments in the UK health service have impacted the the first biosimilar monocloncal antibodies. This year sees the launch sphere of biologic therapy for patients with inflammatory arthritis. of an anti-TNF biosimilar in the UK. The advent of this new class of These include the availability of several new licensed treatments, the drug has attracted widespread attention, including from commis- development of biosimilars and access to biologics influenced by sioners who recognize a potential cost saving. This talk will review updated clinical guidelines and pathways and technological apprai- the challenges facing the introduction of biosimilars into rheumatol- sals issued by the NICE. There have also been changes in ogy practice in the UK, recapping the essential information relevant commissioning arrangements resulting from the enactment of the to the practicing rheumatologist. The concept of biosimilars will be Health and Social Care Act 2012, which aims to liberate the NHS reviewed, highlighting key terminology and clarifying differences (England) by giving patients more choice and clinicians more control. between generics, biosimilars and biocopies. The current EMA Information from the British Society of Rheumatology Biologics requirements for licensure will be outlined, highlighting relevant Register (BSRBR) tracking the progress of patients taking biologic aspects that inform our understanding of drug comparability. therapies for RA and AS has also provided insight into the long-term Specific issues surrounding comparing efficacy and safety to safety profile of biologic agents. The role of biologic therapies in the originator products, including immunogenicity profiles, will be treatment and management of patients with inflammatory joint discussed. The published clinical trial data for Remsima and diseases has continued to evolve and is an area that has significant Inflectra will be summarized. Finally, lessons learnt from our implications for all practitioners. Biologic agents are generally colleagues around the globe who have been using biosimilars will effective, well tolerated and safe in most patients, however, they be shared, covering topics such as the appropriateness of can increase the risk of complications, including infection. As the extrapolating trial data across disease indications. safety of patients is paramount, this risk can be reduced by careful Disclosure statement: J.G. has received honoraria from Pfizer, MSD assessment and monitoring. The aim of this document is to support and Roche; and has received research support from Pfizer. practitioners in the safe and effective assessment, screening and management of patients needing biologic therapies. It provides practitioners with practical information to help them care for patients I119. CURRENT CHALLENGES FROM A PATIENT with different forms of inflammatory arthritis, in all care settings to PERSPECTIVE REGARDING BIOLOGICS develop a standardized approach to caring for patients receiving 1 biologic therapies. We carried out a review of all relevant publica- Ailsa Bosworth 1 tions, resources, guidelines, technology appraisals and summary of National Rheumatoid Arthritis Society, UK product characteristics of biologic therapies and included key resources around shared decision making, commissioning and Abstract not provided. safety. The guideline has two main sections: adults and children. Disclosure statement: The author has declared no conflicts of Within the adult section there are two subheadings. In the first interest. i22 Tuesday 28 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

Disclosure statement: The authors have declared no conflicts of RA OUTCOMES AND COMORBIDITIES interest.

O02. THE OUTCOME AND COST EFFECTIVENESS OF NURSE LED CARE IN THE COMMUNITY IN PEOPLE WITH O01. ANTI-CARBAMYLATED PROTEIN ANTIBODIES ARE RHEUMATOID ARTHRITIS: A PRAGMATIC STUDY ASSOCIATED WITH LONG TERM DISABILITY AND DISEASE 1 2 1 ACTIVITY IN PATIENTS WITH EARLY INFLAMMATORY Richard A. Watts , Janice Mooney , Garry Barton , 1 1 1 ARTHRITIS: RESULTS FROM THE NORFOLK ARTHRITIS Alex J. MacGregor , Lee Shepstone , Lisa Irvine and 1 REGISTER David G. I. Scott 1Norwich Medical School, University of East Anglia and 2School of 1 2 3,4 Jenny H. Humphreys , Marije K. Verheul , Anne Barton , Nursing, University of East Anglia, Norwich, UK Tarnya Marshall5,BoFu1, Rene M. Toes2, 1,4 2 Deborah P. M. Symmons , Leendert A. Trouw and Background: RA affects 0.8% of the UK population. Care is 1 Suzanne M. M. Verstappen traditionally provided in a secondary care setting. Over the past two 1 Arthritis Research UK Centre for Epidemiology, University of decades rheumatology nurse practitioners have become a key part of 2 Manchester, Manchester, UK, Department of Rheumatology, Leiden the multidisciplinary team. We have developed a model of care in 3 University Medical Center, Leiden, The Netherlands, Arthritis which rheumatology nurse practitioners see RA patients independently Research UK Centre for Genetics and Genomics, University of in the community. The aim of the study was to determine the outcome Manchester, 4NIHR Manchester Musculoskeletal Biomedical and cost effectiveness of rheumatology nurse practitioners led care in Research Unit, Manchester Academic Health Science Centre, the community for people with RA, compared with traditional Manchester and 5Department of Rheumatology, Norfolk and Norwich secondary care. University Hospital, Norwich, UK Methods: In a single-area, pragmatic, non-randomized study we assessed the outcome, cost effectiveness of community based Background: Anti-carbamylated protein antibody (anti-CarPA) has rheumatology nurse practitioners led care compared with traditional been shown to predict development of RA in patients with arthralgia. hospital based care. Community based care took place in seven However, little is known about their association with disease activity general practices. Patients were referred to secondary care for and long term outcomes such as disability; or whether they provide consultant opinion for initiation of new drug therapy and steroid additional prognostic information to ACPAs. This study aimed to injections and then returned to community care. Participants were 394 investigate the association between anti-CarPA status, disability and adults with stable RA. Patients were assessed at 1, 6 and 12 months. disease activity in up to 20 years follow up in patients with early Outcome was assessed using the HAQ and EQ-5D We used a inflammatory arthritis (EIA), and examine these associations in patients previously developed health resource use questionnaire. The eco- with and without ACPA. nomic evaluation [National Health Service (NHS)] and healthcare Methods: The Norfolk Arthritis Register recruited adults with recent perspectives) estimated cost relative to change in HAQ and quality- onset swelling of 2 joints for 4 weeks since 1990. Baseline adjusted life years (QALY) derived from EQ-5D. assessment included joint examination, smoking status and patient Results: The demographics and baseline characteristics of patients in recording of the HAQ. CRP, ACPA and anti-CarPA were measured on the community group (192) were comparable to those under hospital stored sera obtained at baseline or in the first year of follow up. DAS care (154). 116 in the community group and 90 in the hospital group for 28 joints (DAS28)-CRP was calculated and 2010 ACR/EULAR completed EQ-5D and health resource use questionnaire at 0, 6 and classification criteria for RA applied. HAQ scores were repeated at 1, 12 months. The mean number of rheumatology nurse practitioners 2, 3, 5, 7, 10, 12, 15 and 20 years of follow up, and DAS28-CRP every 5 contacts was higher in the community group (2.24) compared with the years. Generalized estimating equations (GEEs) were used to test the hospital group (1.37). Mean health professional contact costs were association between anti-CarPA status and longitudinal HAQ and marginally higher for the hospital group (£634 compared with £621). DAS28 scores. Analyses were repeated in the ACPA-negative and There was little difference between the two groups with regard to the ACPA-positive subgroups and in patients fulfilling RA criteria. mean cost associated with hospital / day-case admissions, steroid use Results: 1995 patients were included: 1310 (66%) were female, the or tests and procedures. The largest determinant of overall cost was median [interquartile range (IQR)] age was 55 (43–66) years and symptom biologic drug use. At baseline drug use was £538 compared with £225 duration 33 (17–68) weeks. Anti-CarPA were positive in 460 (23%) in hospital, reflecting an imbalance in the use of biologics. The mean patients; the median (IQR) follow up time was 7 (5–11) years. Baseline incremental total NHS cost was estimated to be £224 less for the median HAQ and DAS28 score were higher in anti-CarPA-positive vs anti- hospital group compared with the community group, with wide CIs (CI CarPA negative patients (1.125 vs 0.875 and 4.23 vs 3.73, respectively). In £213, £701). Excluding patients prescribed biologic drugs commu- the GEE analysis, patients who were anti-CarPA positive had significantly nity care remained more expensive £234 (CI £201, £669. Comparing higher levels of disease activity and disability than those who were the health resource costs to clinical outcomes, as measured by the negative [multivariate model for the HAQ, b-coefficient (95% CI) was 0.18 HAQ, we found the community group had higher mean costs (0.10, 0.25); Table 1]. Statistically significant associations were also seen [difference £127 (CI £369, £624)] and a higher level of functional in the ACPA-negative subgroup. In the ACPA-positive and RA subgroups, disability [HAQ; 0.096 (CI 0.02, 0.21)]. However, the difference in there were significant associations with DAS28 and trends approaching HAQ was not clinically significant. statistical significance with HAQ scores. Conclusion: The results show that community care is associated with Conclusion: The presence of anti-CarPA is associated with increased higher costs but no significant difference in clinical outcome as burden of disability and higher disease activity over time in patients measured by HAQ, EQ-5D and the EQ visual analogue scale. with EIA. Anti-CarPA may be useful for identifying ACPA-negative Disclosure statement: The authors have declared no conflicts of patients with poor prognosis. interest.

O01 TABLE 1. Association between anti-CarpA positivity and HAQ and DAS28 throughout follow up Total cohort, ACPA negative, ACPA positive, RA patients, b-coefficient (95% CI) b-coefficient (95% CI) b-coefficient (95% CI) b-coefficient (95% CI) n 1995 1092 373 1221 HAQ Univariate 0.20 (0.13, 0.28) 0.16 (0.02, 0.31) 0.13 (–0.01, 0.28) 0.06 (–0.03, 0.15) Multivariatea 0.18 (0.10, 0.25) 0.14 (0.01, 0.27) 0.10 (–0.04, 0.24) 0.06 (–0.02, 0.15) DAS28 Univariate 0.47 (0.33, 0.61) 0.29 (0.03, 0.55) 0.30 (0.03, 0.56) 0.16 (0.01, 0.32) Multivariatea 0.39 (0.27, 0.51) 0.23 (0.01, 0.45) 0.24 (0.01, 0.47) 0.18 (0.04, 0.31) aAdjusted for age at symptom onset, gender, disease duration, baseline smoking status, ever use of DMARDs and year of inclusion in the cohort. DAS28: DAS for 28 joints. BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS Tuesday 28 April 2015 i23

O03. AUDIT: ARE RHEUMATOID ARTHRITIS PATIENTS years and therefore were routinely vaccinated based on their age, as MANAGED APPROPRIATELY IN PRIMARY CARE? opposed to their diagnosis. Similarly, all patients screened for depression were patients already with depression and were on Kabir S. Sandhu1, Amrita K. Mankia2 and Param Jeet S. Sandhu3 1 pharmacological treatment. The primary recommendation is to Barts and the London School of Medicine and Dentistry, London, incorporate these two interventions into the annual review, perhaps 2Rheumatology, Buckinghamshire Healthcare NHS Trust, Aylesbury 3 through the use of pop-up alerts on the computer system. and General Practice, Hammond Road Surgery, Southall, UK Disclosure statement: The authors have declared no conflicts of interest. Background: RA is an autoimmune condition with a worldwide prevalence of 1%. The approach to treatment has evolved due to novel therapeutic agents and management regimens assessing O04. DEFINING THE CHARACTERISTICS OF REMISSION systemic, as well as joint, involvement. The rationale for monitoring AND LOW DISEASE ACTIVITY STATE IN PATIENTS WITH systemic effects of RA is their association with a poorer prognosis. RHEUMATOID ARTHRITIS: CLINICAL, IMAGING, Cardiovascular disease (CVD) is recognized as the leading cause of FUNCTIONAL AND IMMUNOLOGICAL CHARACTERISTICS death, accounting for 40% mortality. Meta-analyses indicate the prevalence of depression to be 38.8%. Furthermore, greater incidence Hanna L. Gul1, Maria J. Isorna Porto1, Frederique Ponchel1, of fractures and respiratory tract infections occur, as compared with the Elizabeth M. A. Hensor1 and Paul Emery1 general population. This audit aims to evaluate the management of 1Rheumatology, Leeds Institute of Rheumatic and Musculoskeletal systemic RA in a general practice setting, as recommended by National Medicine, University of Leeds, Leeds, UK Institute for Health and Care Excellence and Arthritis Research UK. Methods: All RA patients over 16 years of age registered at Hammond Background: Although remission is the goal of treatment in RA, Road Surgery were audited. The SystmOne practice database was current remission criteria are largely subjective and do not consider searched between October and November 2014. The audit criteria structural damage, physical function or subclinical inflammation. Thus were the percentage of patients with RA who had received an annual the validity of these criteria remains questionable. We aimed to explore review in the preceding 15 months; aged 30–84 years who had the clinical, imaging, functional and immunological characteristics of received a CVD risk assessment in the preceding 15 months; who had RA patients in clinical remission [DAS for28 joints (DAS28)-CRP < 2.6 been offered appropriate interventions to reduce CVD; screened for and/or low disease activity state (LDAS; DAS28-CRP 3.2)] to better depression; aged 50–90 years who had received an assessment of understand the remission phenotype; which may help to describe a fracture risk in the preceding 27 months; and offered influenza and true remission state. pneumococcus immunizations. The audit target was 100%. Methods: A retrospective observational study was performed using Results: A total of 5100 patients were registered at the practice. 31 RA our inflammatory arthritis database. Patients were selected when patients were eligible, resulting in a practice prevalence of 0.61%. The fulfilling the inclusion criteria of an RA diagnosis (1987 or 2010 ACR/ mean age was 64.2 years. 29 (90%) patients were South-East Asian EULAR criteria); and a DAS28-CRP of 3.2. The lowest observation of and 23 (74.2%) were female. All patients had established RA (more DAS28-CRP after diagnosis was prioritized. Disease/remission dura- than 2 years since diagnosis) as per the Guideline Development Group tion and treatment modality was not considered. We collected data on criteria. Patients meeting each audit criterion are presented: annual RA tender and swollen joint counts (TJC28/SJC28), inflammatory markers, review (n ¼ 26; 83.9%); CVD risk assessment (n ¼ 25; 80.6%); CVD autoantibody status, patient-reported outcome measures and US and reduction interventions (n ¼ 25; 80.6%); fracture risk assessment X-ray findings. Furthermore, T-cell subsets (naiveCD4þT cells, inflam- (n ¼ 22; 71.0%); vaccinations (n ¼ 16; 51.6%); and depression screen mation-related cells (IRCs) and regulatory T cells (Tregs) were analysed (n ¼ 8; 25.8%). The RA-adjusted risk assessment tools used were by advanced eight-colour flow cytometry. Frequencies of subsets QRISK for CVD, FRAX for fractures and PHQ-9 for depression. were compared with reference range values obtained from 120 healthy Conclusion: The practice prevalence is lower than the average controls. prevalence and therefore the pick-up of RA is poor, possibly due to Results: We included 633 patients with a minimum DAS28-CRP score a lower prevalence in the South-East Asian diaspora. Annual RA of 3.2 (mean 1.85, S.D. 0.67). Of these, 513 were in strict remission reviews, CVD management and fracture screening occurred most (DAS28-CRP < 2.6), the mean age was 57.6 years (20–88) and 68.7% frequently, possibly because these tasks were notified to the clinician were female. Table 1 summarizes the data of our cohort. Active electronically. Offering vaccinations and depression screening did not synovitis, confirmed by positive power Doppler signal was present in occur as readily. All patients vaccinated were above the age of 65 nearly two-thirds of patients in LDAS and almost half of those in

O04 TABLE 1. General characteristics and characteristics used to refine remission Characteristic DAS28-CRP 2.6–3.2 (n ¼ 120) DAS28-CRP < 2.6 (n ¼ 513) General characteristics Autoantibody status, % (n/n) RF positive 67.3 (76/113) 58.1 (266/458) ACPA (anti-CCP) positive 69.7 (83/119) 70.1 (351/501) Patient-reported outcomes, median (1st quartile, 3rd quartile); range (n) HAQ-DI 1.06 (0.47, 1.88); 0.0–3.0 (102) 0.38 (0.00, 1.13); 0.0–2.63 (442) RAQoL 11.00 (3.03, 21.00); 0.00–30 (100) 4.00 (1.00, 11.90); 0.0–30 (425) VAS general health 38.50 (16.5, 57.25); 0.0–99 (102) 19.00 (6.00, 39.00); 0.0–93 (438) VAS pain 38.00 (11.00, 61.00); 0.0–98 (101) 14.00 (4.00, 34.00); 0.0–95 (435) VAS disease activity 35.00 (14.50, 67.00); 1.0–100 (100) 12.00 (4.00–37.00); 0.0–92 (435) EQ-5D 0.69 (0.52, 0.76); –0.24–1.00 (97) 0.80 (0.66, 1.00); –0.24–1.00 (392) Characteristics used to refine remission, % (n/n) Acute phase reactants CRP < 5 mg/l 47.1 (56/119) 81.9 (420/513) CRP 5–10 mg/l 25.2 (30/119) 11.7 (60/515) CRP > 10 mg/l 27.7 (33/119) 6.4 (33/513) Range 0–83 0–38 ESR > 15 mm/h 61 (61/100) 34.5 (151/438) Range 2–128 1–92 Joint counts, % (n/n) SJC28 ¼ 0 46.7 (56/120) 84.0 (431/513) SJC28 ¼ 1 18.3 (22/120) 9.2 (47/513) SJC28 ¼ 2 or more 35.0 (42/120) 6.8 (35/513) TJC28 ¼ 0 11.7 (14/120) 68.6 (352/513) TJC ¼ 1 21.7 (26/120) 13.8 (71/513) TJC ¼ 2 or more 66.7 (80/120) 17.5 (90/513) Imaging, % (n/n) Power Doppler present (any >0) 65.3 (47/72) 43.2 (140/324) Grey-scale score of >1in1 joint 86.1 (62/72) 76.2 (247/324) X-ray erosions reported 36.1 (39/108) 31.7 (145/458) DAS28: DAS for28 joints; HAQ-DI: HAQ disability index; SJC28: swollen joint count for 28 joints; TJC28: tender joint count for 28 joints; VAS: visual analogue scale. i24 Tuesday 28 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

remission. A grey scale score of >1in1 joint was present in 78% consisted of MTX plus another DMARD (84% occasions). (309/396) patients; its prevalence was similar in LDAS and remission. Commensurate with the increased early use of MTX and combination The group had generally low levels of functional impairment/disability therapy over time, recruitment year was significantly associated with and life impairment, and these are even lower in the remission patients. all-cause mortality risk [hazard ratio (HR) 0.96 (95%CI 0.95, 0.98), T cell subset analysis was available for 51 patients. Abnormal P < 0.001). The weighted pooled logistic survival models indicated that frequencies were observed in 11.8% of patients for naiveCD4þT MTX use was associated with around a 60% reduction in the risk of cells, 27.5% for IRCs and 54.9% for Tregs. Five patients were in LDAS; death [HR 0.43 (95%CI 0.21, 0.51), P < 0.001]. Use of combination abnormal cell frequencies were found in two patients for naiveCD4– T therapy was also associated with around a 60% reduction in the risk of cells, three for IRCs and all had abnormal Treg frequencies. For death [HR 0.39 (95%CI 0.22, 0.68), P < 0.001]. After controlling for the patients in remission, the corresponding proportions with abnormal treatment variables, recruitment year was not related to mortality risk cell frequencies were 8.7% (4/46), 23.9% (11/46) and 50% (23/46) for [HR 1.01 (95%CI 0.98, 1.04), P ¼ 0.566]. naiveT cells, IRCs and Tregs, respectively. Conclusion: MTX and combination therapy are related to a substantial Conclusion: Despite being in clinical/DAS remission or LDAS, a decrease in mortality risk. The greater use of these treatments over substantial proportion of patients exhibited subclinical inflammation on time appears to account for the majority of the decreased all-cause US. This was slightly higher for patients in LDAS. Non-normalization of mortality rate in RA. T-cells was also observed in both LDAS and remission. Current Disclosure statement: The authors have declared no conflicts of remission criteria are composite scores and do not measure interest. inflammation at the primary site of pathology. Identification of remission biomarkers could potentially help predict the ability to O06. IMPACT OF ACHIEVING LOW DISEASE ACTIVITY ON sustain remission and facilitate treatment withdrawal strategies, GENERAL HEALTH STATUS leading to better understanding of what constitutes true remission. Disclosure statement: The authors have declared no conflicts of Aneela N. Mian1, David L. Scott1, Gabrielle H. Kingsley1 and interest. Fowzia Ibrahim1 1Rheumatology, King’s College London, London, UK

Young Investigator Award Background: The EuroQol (EQ-5D), a patient-reported outcome, characterizes health status from 0 (death) to 1 (normal health). It can O05. IMPACT OF CONVENTIONAL DISEASE MODIFYING be used to calculate Quality Adjusted Life Years (QALYs), allowing it to THERAPY ON MORTALITY RISK IN TWO UK RHEUMATOID be used in health economic analyses. We explored the impact of ARTHRITIS COHORTS controlling disease activity with intensive treatment regimens on health Sam Norton1, Elena Nikiphorou2,3, Lewis Carpenter4, David Walsh5, utility using EQ-5D scores. Our hypothesis was that only low disease Patrick Kiely6, Josh Dixey7 and Adam Young2,3 activity or remission states would achieve substantial increases in 1Psychology Department, Institute of , King’s College EQ-5D. London, London, 2ERAS & ERAN, St Albans City Hospital, St Albans, Methods: We undertook secondary analyses of two randomized 3School of Life & Medical Sciences, 4Centre for Lifespan & Chronic controlled trials to examine the relationship between disease activity Illness Research Centre, University of Hertfordshire, Hatfield, and improvements in EQ-5D scores: an early RA trial, intensive 5Arthritis UK Pain Centre, University of Nottingham, Nottingham, DMARDs in 467 patients; and an established RA trial, intensive 6Rheumatology, St George’s Healthcare Trust, London and DMARDs or tumour necrosis factor inhibitors (TNFis) in 205 patients. 7Rheumatology, New Cross Hospital, Wolverhampton, UK Disease control was divided into four categories based on DAS for28 joints (DAS28) scores: low disease/remission, < 3.2; low intermediate, Background: RA is associated with an increased risk of mortality from 3.2–4.0; high intermediate, 4.0–5.1; and active, >5.1. We compared all-causes compared with the general population, though there is increases in mean EQ-5D scores in these different DAS28 groups. some suggestion that this excess mortality risk is reducing. The aim of Results: Only patients achieving DAS28 scores of < 3.2 achieved the present study is to examine the effect of conventional disease substantial improvements in EQ-5D scores (Table 1). Patients with modifying treatment on mortality, and to determine whether this active disease had no or minimal improvements. Intermediate disease accounts for any decrease in mortality risk over time. gave modest improvements in EQ-5D. Improvements in EQ-5D scores Methods: 2701 patients were recruited between 1986 and 2012, from in patients achieving low disease activity or remission were similar in 31 centres in the UK and a single centre in Ireland, to two consecutive early and established RA and with both intensive DMARD and biologic inception cohort studies: the Early RA Study (n ¼ 1465) and the Early treatment. RA Network (n ¼ 1236). For both cohorts, information on demographic Conclusion: Intensive treatment only results in substantial improve- and clinical information, including treatment, was recorded at baseline, ments in EQ-5D scores if patients achieve low disease activity or after 3–6 months, after 12 months and then yearly. Data from both remission. This relationship is seen in early and established RA and cohorts were combined for analysis. In total, 826 individuals were with conventional or biologic strategies. The health economic known to have died by November 2013. The effect of MTX and justification for high cost biologics, which reflects improved EQ-5D combination therapy on mortality risk was estimated using pooled scores, is strong when patients achieve remission or low disease logistic survival models, including inverse probability (of treatment) activity, but weaker when disease control is less marked. We have weights. Weights were necessary to account for greater use of MTX used directly measured EQ-5D scores to try, but it is important to note and combination therapy use among individuals with worse disease that many economic models convert HAQ to EQ-5D, which although (confounding by indication), which would have led to a biased estimate allowing some estimations to be made, are not directly related. We of the causal effect of treatment on mortality risk. recommend intensive treatment strategies target low disease activity Results: Use of MTX within the first 6 months of disease increased or remission. The data also raise some interesting questions about the dramatically over the period of recruitment: from 3.6% in ERAS cost effectiveness of biologics where there is a moderate response but (recruitment 1986 to 2001) to 54.9% in ERAN (recruitment 2002 to remission or low disease activity is not achieved. 2012). Similarly combination therapy within 6 months increased from Disclosure statement: The authors have declared no conflicts of 3.2% in ERAS to 15.7% in ERAN; where combination therapy typically interest.

O06 TABLE 1. Increase in EQ-5D with treatment by DAS28 category Disease Treatment DAS28 category

<3.2 3.2–4.0 4.0–5.1 >5.1 Early RA DMARDs 0.21 (0.16, 0.26) 0.22 (0.14, 0.29) 0.11 (0.06, 0.16) 0.01 (0.05, 0.06) Established RA DMARDs 0.31 (0.17, 0.46) 0.20 (0.06, 0.33) 0.14 (0.011, 0.28) 0.08 (0.24, 0.18) Biologics 0.28 (0.18, 0.38) 0.18 (0.05, 0.31) 0.23 (0.10, 0.36) 0.07 (0.05, 0.18)

Values are mean (S.E.M.). DAS28: DAS for28 joints. i25 Tuesday 28 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

lymphoma, in particular diffuse large B-cell lymphoma (DLBCL) is greatest in patients with persistently active RA: those patients that are BIOLOGICS AND INFLAMMATORY also most likely to receive biologics. There has been a concern that ARTHRITIS TNF inhibitors (TNFis) could increase the risk of lymphoma via reduced immunosurveillance. Conversely, TNFis may, by improving disease control, decrease the lymphoma risk, especially risk of DLBCL. This abstract describes a EULAR initiative to describe the spectrum of O07. FIRST RESULTS OF A EUROPEAN REGISTRIES lymphomas occurring in biologic-naivepatients with RA and those COLLABORATIVE PROJECT TO DESCRIBE THE SPECTRUM treated with biologics. OF LYMPHOMAS ACROSS DIFFERENT DRUG TREATMENT Methods: Patients with RA were included from 11 European biologics GROUPS IN RHEUMATOID ARTHRITIS registers in 8 countries and followed prospectively for the occurrence of first ever lymphoma, confirmed with histology. Patients were 1 2 1 3 Louise Mercer , Xavier Mariette , Will Dixon , Eva Baecklund , considered to be exposed to a biologic agent after receiving the first 4 5 6 7 Karin Hellgren , Lene Dreyer , Merete Hetland , Lene Mellemkjær , dose and lymphomas were attributed to the most recently received 1 8 8 9 Kimme Hyrich , Anja Strangfeld , Angela Zink , Helena Canhao , biologic drug. For the TNFi cohort, prior exposure to biologic drugs 9 10 11 Fernando Martins , Victoria Herna´ ndez , Florence Tubach , was not permitted. Prior exposure to TNFi was allowed for other 12 13 14 Jacques-Eric Gottenberg , Jacques Morel , Jakub Zavada , biologic drugs. Frequency of lymphoma subtypes was recorded for 15 1,6 17 4 Piet van Riel , Axel Finckh , Florenzo Iannone , Johan Askling each drug class. 8 and Joachim Listing Results: Data for 130 462 patients were available for the analysis 1 Arthritis Research UK Centre for Epidemiology, University of (Sweden, n ¼ 61 527; Denmark, n ¼ 21 454; UK, n ¼ 17 907; Germany, 2 Manchester, Manchester, UK, Department of Rheumatology, n ¼ 12 581; Portugal, n ¼ 5031; Spain, n ¼ 4590; France, n ¼ 4512; 3 Universite Paris-Sud, Paris, France, Department of Medical Czech Republic, n ¼ 2860): the mean age was 59 years and 74% 4 Sciences, Uppsala University, Uppsala, Clinical Epidemiology Unit, female. In total, 520 lymphomas with subtype information were Karolinska Institutet, Stockholm, Sweden, 5Department of included in Table 1. Patient-years were available for 493 Rheumatology, Gentofte University Hospital, Hellerup, 6DANBIO, lymphomas, corresponding to an overall crude incidence rate (IR) Copenhagen Center for Arthritis Research, University of of 8.3 (95% CI 7.6, 9.1). DLBCL was the most frequent subtype Copenhagen, 7Danish Cancer Society Research Centre, Danish (37% of all lymphomas; Table 1). 9% of lymphomas were HL and 6% Cancer Society, Copenhagen, Denmark, 8Epidemiology Unit, were T cell, with no cases of hepatosplenic T cell lymphoma. German Rheumatism Research Centre, Berlin, Germany, Importantly, the distribution of subtypes was similar across treatment 9Rheumatology Research Unit, Universidade de Lisboa, Lisbon, groups. Portugal, 10BIOBADASER Registry, Madrid, Spain, 11De´ partement Conclusion: This large collaborative analysis of European registries d’Epide´ miologie et Recherche Clinique, Universite´ Paris Diderot, has successfully collated subtype information on more than 500 Paris, 12Department of Rheumatology, CHU, Strasbourg, 13Universite lymphomas. There was no evidence of modification of the distribution Montpellier, Montpellier, France, 14Institute of Rheumatology, of lymphoma subtypes reported in patients following exposure to Charles University, Prague, Czech Republic, 15Department of biologics. This collaboration facilitates more detailed analyses, Rheumatic Diseases, Radboud University, Nijmegen, The accounting for age, sex, country and specific TNFi, as well as RA- Netherlands, 16University of Geneva, Geneva, Switzerland and related factors. 17University of Bari, Bari, Italy Disclosure statement: J.M. has received consulting fees from Roche Pharmaceuticals, Pfizer, Bristol-Myers Squibb, Union Chimique Belge, Background: RA is associated with a 2–3 fold increased risk of both Merck Pharmaceuticals and Abbott Laboratories. All other authors Hodgkin and non-Hodgkin lymphoma (HL, NHL). The risk of have declared no conflicts of interest.

O07 TABLE 1. Subtypes of lymphoma reported in biologic-naiveand cohorts of patients with RA All Biologic-naive TNFi Rituximab Tocilizumab Abatacept Patients in cohort, n 130462 71866 41078 9880 4800 2838 Total follow up time, person-years 592245 322422 226080 30606 7122 6015 Female, % 774 72 77 79 80 78 Age, mean 59 61 55 58 56 57 Total number of lymphomas 520a 288 219a 652 Lymphoma subtypes, n (% of cohort) Hodgkin lymphoma 45 (9) 21 (7) 24 (11) 0 0 0 B cell lymphomas 389 (75) 220 (76) 157 (72) 5 (83) 5 (100) 2 (100) Chronic lymphocytic / small cell 55 (11) 28 (10) 24 (11) 1 (17) 2 (40) 0 B cell HHL lymphoplasmacytic (Waldenstrom macroglobulinaemia) 11 (2) 4 (1) 6 (3) 1 (17) 0 0 Marginal zone 9 (2) 1 (0) 8 (4) 0 0 0 Follicular 67 (13) 33 (11) 32 (15) 1 (17) 0 1 (50) Mantel cell 5 (1) 5 (2) 0 0 0 0 Diffuse large B cell 194 (37) 113 (39) 75 (34) 2 (33) 3 (60) 1 (50) Unspecified B cell 48 (9) 36 (13) 12 (5) 0 0 0 T cell lymphomas 32 (6) 17 (6) 14 (6) 1 (17) 0 0 Peripheral T cell 12 (2) 6 (2) 5 (2) 1 (17) 0 0 Angioimmunoblastic 5 (1) 3 (1) 2 (1) 0 0 0 Anaplastic large cell 1 (0) 1 (0) 0 0 0 0 LGL T cell 0 0 0 0 0 0 Pleomorphic T cell 2 (0) 0 2 (1) 0 0 0 Hepatosplenic T cell 0 0 0 0 0 0 Unspecified T cell 12 (2) 7 (2) 5 (2) 0 0 0 Unspecified non-Hodgkin lymphoma/lymphoma 53 (10) 30 (10) 23 (11) 0 0 0 All percentages represent the % of the total number of patients with lymphoma in that cohort with Hodgkin lymphoma, B and T cell lymphomas and unspecified non- Hodgkin lymphoma or lymphoma (totalling 100%). a27 lymphomas, but no follow-up time, are included from the RATIO registry, France. HHL: heavy-heavy and heavy-light chanins;LGL: large granular lymphocytic. i26 Tuesday 28 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

O08. IMPROVEMENTS IN FATIGUE FOLLOWING ANTI-TNF Disclosure statement: N.B. has received consulting fees from Pfizer THERAPY DO NOT REFLECT REDUCTIONS IN and MSD; is a member of the speakers’ bureaus for Pfizer and Roche; INFLAMMATION AND ARE INSTEAD A DOWNSTREAM and has received grants/research support from Pfizer. All other authors CONSEQUENCE OF PAIN IMPROVEMENTS: RESULTS FROM have declared no conflicts of interest. THE BRITISH SOCIETY FOR RHEUMATOLOGY BIOLOGICS REGISTER FOR RHEUMATOID ARTHRITIS O09. FACTORS ASSOCIATED WITH PERSISTENT, 1 1 1 1 Katie L. Druce , Gareth T. Jones , Gary J. Macfarlane and Neil Basu INTERMITTENT OR NEVER ACHIEVING REMISSION IN 1 Epidemiology Group, University of Aberdeen, Aberdeen, UK PATIENTS WITH RECENT-ONSET INFLAMMATORY POLYARTHRITIS: RESULTS FROM THE NORFOLK ARTHRITIS Background: RA-related fatigue improves substantially following anti- REGISTER TNF therapy commencement. It has been shown that, rather than 1 2 3 1 being produced directly by reductions in disease activity, these Michael J. Cook , Janet Diffin , Carlo A. Scire` , Mark Lunt , Alex 4 1 improvements are largely mediated by changes in pain. Yet, as pain J. MacGregor , Deborah P. M. Symmons and Suzanne M. 1 has a complex aetiology, it is not clear whether the observed M. Verstappen 1 improvements in fatigue reflect reductions in centrally or peripherally Arthritis Research UK Centre for Epidemiology, University of (e.g. inflammation) driven pain. In clarifying whether it is inflammatory Manchester, 2School of Nursing, Midwifery and Social Work, pain which should be targeted to reduce fatigue, this study sought to University of Manchester, Manchester, UK, 3Epidemiology Unit, inform optimized future management of this burdensome symptom. Italian Society for Rheumatology, Milano, Italy and 4Norwich Medical Methods: The British Society for Rheumatology Biologics Register for RA School, University of East Anglia, Norwich, UK (BSRBR-RA) comprises a large cohort of patients who commenced anti- TNF therapies between October 2000 and November 2008. Data of Background: Sustained remission is the current aim in the treatment interest from 2652 BSRBR-RA participants with high levels of fatigue of RA. However, patients’ response to treatment varies considerably, (SF36 vitality score 12.5), comprised change over 6 months in fatigue, from achieving persistent remission to no remission at all. The aim of pain (SF36 vitality and bodily pain, respectively) and disease activity this study was to identify whether clinical and demographic factors constituents [DAS for28 joints (DAS28); ESR, global health and swollen and comorbidities are associated with achieving persistent remission and tender joints]. Principal components factor analysis, a data-reduction (PR), intermittent remission (IR) or never achieving remission (NR) in method commonly used to collapse or cluster multiple items into fewer patients with recent-onset inflammatory polyarthritis followed for five theoretical, or unmeasured, constructs (factors), was used to determine years in the Norfolk Arthritis Register (NOAR). common clusters of change in symptoms. The factors which explained a Methods: Patients included in this study were recruited to NOAR, a greater proportion of total variance of all items (indicated eigenvalue >1) primary care based inception cohort of patients with recent-onset than any individual item (variance standardized to 1.0) were accepted. To inflammatory polyarthritis, from 2000 to 2008. Baseline variables maximize factor-loading strength on one factor and minimize cross- collected included age at symptom onset, BMI, CRP, RF, anti-CCP loading (loading > 0.3 on 2 factors) the correlation between each item antibody, DAS for 28 joints (DAS28), HAQ score and self-reported and the factors were rotated using varimax rotation. comorbidities. The 2010 ACR/EULAR criteria for RA were applied at Results: Two factors explained more variance in the data than single baseline. Tender and swollen joint counts (out of 51) were performed at items alone (eigenvalues; factor 1 ¼ 2.39, factor 2 ¼ 1.14). Changes in baseline, 1st, 2nd, 3rd and 5th year anniversaries. Patients were both swollen and tender joint counts, along with change in ESR loaded excluded if their symptom duration at baseline was 2 years or if they most strongly on the first factor, while changes in pain and fatigue, had missing joint counts at 1 follow-up visit. Remission at each follow loaded on the second; change in visual analogue scale global health up was defined as no tender or swollen joints. Patients were classified showed loadings of >0.3 on both factors. With a loading of 0.3, as NR if they were not in remission at any anniversary, IR if they were in changes in ESR only just met factor loading criteria, suggesting a weak remission at least once but 2 consecutive anniversaries and PR if association was present. they were in remission at 3 consecutive anniversaries. Univariate Conclusion: Our findings suggest that changes in fatigue observed ordinal logistic regression was used to assess the association between following anti-TNF therapies share an underlying construct with changes baseline characteristics and being in the IR or PR remission groups in pain, but not with changes in inflammation. Therefore changes in fatigue (NR group as reference; Table 1). do not appear to be a direct effect of the drug reducing inflammation. Results: 868 patients were included in this study; 65.8% female, mean Instead, improvements likely represent the downstream consequence of age at symptom onset 55.9 (S.D. 14.6) years and median disease anti-TNF therapies reducing pain and associated improvements in general duration 6.5 [interquartile range 4.1–11.1] months at baseline. The well-being. Accordingly, it is suggested that, in addition to immunomo- numbers (percentages) of patients achieving NR, IR and PR were 471 dulation, reductions in fatigue could be promoted by a multidisciplinary (54.3%), 296 (34.1%) and 101 (11.6%), respectively. Female sex, management strategy specifically to reduce pain. higher number of swollen or tender joints, satisfying the 2010 RA

009 TABLE 1. Baseline characteristics NR IR PR Univariate ordered P-value logistic regression. (from univariate Remission group ordered logistic (NR, IR, PR) is the regression) dependent variable nnn

Age at onset, mean (S.D.), years 56.49 (14.09) 471 55.05 (14.90) 296 55.95 (15.94) 101 1.00 (0.99, 1.00) 0.30 Symptom duration, 6.74 (4.40–11.56) 471 6.34 (3.93–10.99) 296 5.52 (3.78–10.12) 101 0.98 (0.96, 1.00) 0.09 median (IQR), months Female, % 75.16 354/471 58.11 172/296 44.55 45/101 0.39 (0.29, 0.51) <0.001 Swollen joints (51 count), median (IQR) 5 (2–9) 471 2 (0–5) 296 2 (0–5) 101 0.94 (0.92, 0.96) <0.001 Tender joints (51 count), median (IQR) 8 (3–18) 471 2 (0–8) 296 1 (0–3) 101 0.92 (0.90, 0.94) <0.001 CRP, median (IQR), mg/l 11 (4.1–23.1) 401 11.80 (6.00–21.70) 245 11.25 (4.40–21.70) 88 1.00 (0.99, 1.01) 1.00 RF positive, % 43.12 188/436 44.77 124/277 32.98 31/94 0.88 (0.67, 1.16) 0.37 Anti-CCP antibody positive, % 33.94 131/386 37.04 90/243 21.98 20/91 0.86 (0.64–1.16) 0.33 DAS28, mean (S.D.) 4.13 (1.26) 401 3.38 (1.16) 245 3.07 (1.10) 88 0.57 (0.50, 0.65) <0.001 HAQ, median (IQR) 1.25 (0.63–1.75) 462 0.63 (0.25–1.13) 292 0.50 (0.00–1.00) 99 0.39 (0.32, 0.47) <0.001 Satisfied 2010 ACR/EULAR 54.99 259/471 40.20 119/296 36.63 37/101 0.54 (0.42, 0.70) <0.001 criteria for RA, % Time between symptom onset 6.55 (4.01–12.60) 384 6.24 (3.45–11.01) 237 5.19 (3.02–10.05) 63 0.99 (0.98, 1.00) 0.17 and starting DMARDS, median (IQR), months At least one comorbidity, % 73.25 345/471 64.86 192/296 51.49 52/101 0.55 (0.42, 0.73) 0.55 (0.42, 0.73) Hypertensive, % 43.31 204/471 37.5 111/296 26.73 27/101 0.67 (0.51, 0.87) 0.003 Depressed, % 42.46 200/471 31.76 94/296 19.8 20/101 0.52 (0.40, 0.69) <0.001 Obese (BMI>30), % 32.25 149/462 21.23 62/292 13.13 13/99 0.49 (0.36, 0.66) <0.001 Never smoked 31.55 130/412 34.51 88/255 31.52 29/92 referent referent Current smoker, % 25.00 103/412 21.96 56/255 26.09 24/92 0.95 (0.79, 1.15) 0.61 Smoked in the past, % 43.45 179/412 43.53 111/255 42.39 39/92 0.95 (0.69, 1.30) 0.73 DAS28: DAS for 28 joints; IQR: interquartile range. BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS Tuesday 28 April 2015 i27

criteria, higher HAQ and DAS28 scores, having at least one and were censored at first episode of lupus-like event, switching to comorbidity, being hypertensive, depressed or obese at baseline another biologic, death, last returned physician follow-up or 31 May were all associated with lower odds of achieving IR or PR (Table 1). 2014, whichever came first. Similar results were seen after adjusting for DMARD treatment at Results: There were 55 incident DIL cases: 5 in 3673 nbDMARD baseline and in a sub-analysis of patients who satisfied the 2010 ACR/ patients and 50 in 12 289 first TNFi-treated subjects. The median time EULAR criteria for RA at baseline. to event was lower in the TNFi cohort at 0.75 years (Table 1). After Conclusion: Although the aim of current treatment strategies is adjusting for deciles of propensity, the hazard ratio of DIL in patients sustained remission, we found that only 12% of patients achieved on TNFi vs nbDMARD was 2.95 (95% CI 0.93, 9.41). Systemic sustained remission. A number of modifiable predictors were identified characteristics of these events are described as below (Table 1). Over and further research is warranted to assess the impact of changing half of events following TNFi and nbDMARDs were limited to these factors on achieving sustained remission. cutaneous manifestations and 12–20% fulfilled SLE classification Funding: Financial support was received from GSK (granted to criteria (Table 1). In the nbDMARD and TNFi-treated cohorts, one and M.J.C.). five patients developed biopsy-proven lupus nephritis, respectively. Disclosure statement: The authors have declared no conflicts of There were two deaths in the TNFi-induced DIL group, one directly interest. attributed to the event. Conclusion: The overall incidence of DIL in a TNFi-treated RA treated cohort was 1/1000 person-years. There was an increased risk of DIL on O10. RISK AND CHARACTERISTICS OF DRUG-INDUCED TNFi vs nbDMARD, although this was not significant after deciles of LUPUS IN PATIENTS EXPOSED TO TUMOUR NECROSIS propensity adjustment. TNFi-induced lupus encompasses a spectrum of FACTOR-a INHIBITOR THERAPY: RESULTS FROM THE characteristics, but the majority do not fulfil SLE classification criteria. BRITISH SOCIETY FOR RHEUMATOLOGY BIOLOGICS Disclosure statement: M.J. has received honoraria from Pfizer and REGISTER FOR RHEUMATOID ARTHRITIS UCB. I.B. has received honoraria from GSK, Roche and Pfizer; and has Meghna Jani1, Lianne Kearsley-Fleet1, William G. Dixon1, received grants/research support from GSK, Roche and UCB. H.C. Ian Bruce1,2, Hector Chinoy2,3, Anne Barton2,3, Mark Lunt1, has received honoraria from AbbVie, Roche, Janssen, MSD, Pfizer, Kath Watson1, Deborah Symmons1 and Kimme Hyrich1 UCB, Celgene and Servier. A.B. has received grants/research support 1Arthritis Research UK Centre For Epidemiology, 2NIHR Manchester from Pfizer, AbbVie, Eli-Lilly and Sanofi-Aventis. K.H. has received Musculoskeletal Biomedical Research Unit and 3Centre for honoraria from AbbVie and Pfizer. All other authors have declared no Musculoskeletal Research, University of Manchester, Manchester, UK conflicts of interest.

Background: Although TNF-a inhibitor (TNFi) therapies for the O11. CLINICAL UTILITY OF RANDOM ANTI-TNF DRUG treatment of RA are known to induce anti-nuclear antibodies, TNFi- LEVEL TESTING AND MEASUREMENT OF ANTI-DRUG induced lupus is a rare but well-recognized phenomenon. The ANTIBODIES ON LONG-TERM TREATMENT RESPONSE IN incidence and characteristics of RA patients that develop this adverse RHEUMATOID ARTHRITIS event remain poorly defined. The aims of this study were to compare Meghna Jani1, Hector Chinoy1,2, Richard B. Warren3, Christopher E. the incidence of drug-induced lupus (DIL) in subjects with RA treated 3 1,2 4 5 with TNFi to those receiving non-biologic drugs (nbDMARDs) and M. Griffiths , Darren Plant ,BoFu, Ann W. Morgan , Anthony G. Wilson6, John D. Isaacs7, Kimme L. Hyrich1 and Anne Barton1,2 characterize these adverse events. 1 2 Methods: The British Society for Rheumatology Biologics Register for Centre for Musculoskeletal Research, NIHR Manchester 3 RA (BSRBR-RA) is a prospective cohort study assessing the safety of Musculoskeletal Biomedical Research Unit, The Dermatology 4 biologic therapy. This analysis included two cohorts: patients starting Centre, University of Manchester, Centre for Biostatistics, 5 TNFi (adalimumab, etanercept, infliximab, certolizumab); and a biologic- Manchester, Leeds Institute of Rheumatic and Musculoskeletal 6 naivecomparison cohort receiving nbDMARDs. Patients were recruited Medicine, University of Leeds, Leeds, Academic Unit of to the study between 2001 and 2014. Additional information from Rheumatology, University of Sheffield, Sheffield, 7Musculoskeletal consultants was sought for all incident DIL events. Events were classified Research Group, Institute of Cellular Medicine, Newcastle University as DIL if they met 2 criteria as described by the Dubois’ guidelines. and National Institute of Health Research Newcastle Biomedical Briefly this includes treatment with known lupus-inducing drug for 1 Research Centre, Newcastle upon Tyne, UK month; mucocutaneous/constitutional symptoms within the lupus spectrum; multisystem involvement especially neurological, renal and Background: Up to 40% of RA patients on TNF-a treatment fail to skin symptoms; immunological or haematological laboratory profile respond due to primary or secondary inefficacy. One explanation is consistent with lupus; and improvement/resolution of symptoms after immunogenicity due to anti-drug antibody (ADAb) formation and drug discontinuation. Only patients who were biologic-naiveat baseline ensuing sub-therapeutic blood drug levels. The clinical utility of were included and those with pre-existing overlap with SLE excluded, to pharmacological monitoring is disputed partly because the practical- assess the incidence. The risk of an event was compared between the ities of obtaining trough drug levels could impact on service delivery. two cohorts using Cox regression, adjusted using deciles of propensity Our aims were to evaluate whether the presence of ADAbs and/or scores. Events were attributed to TNFi therapy if they occurred on drug non-trough drug levels predict treatment response in anti-TNF treated

O10 TABLE 1. Patient characteristics and risk of first lupus-like event (on first drug) nbDMARD (n ¼ 3673) TNFi (n ¼ 12 289) Age, median (IQR) 61 (52–69) 57 (48–65) Person-years of exposure, pyrs 19 380 47 541 Number of DIL events, n (%) 5 (0.1) 50 (0.4) Crude incidence rate of DIL per 10 000 pyrs (95% CI) 2.58 (1.07, 6.20) 10.53 (7.98, 13.89) Time to first event, years, median (IQR) 2.69 (1.37–2.75) 0.75 (0.18–1.68) Risk of lupus-like events between nbDMARD and TNFi (on drug) Unadjusted hazard ratio (95% CI) Referent 3.75 (1.49, 9.43)* Age and gender adjusted hazard ratio (95% CI) Referent 3.61 (1.42, 9.09)* Deciles of propensity-adjusted hazard ratio (95% CI) Referent 2.95 (0.93, 9.41) Characteristics of DIL Number of events on individual drug, n (%) Penicillamine: 1 (20) Etanercept: 17 (34) AZA: 1 (20) Infliximab: 24 (48) MTX only: 1 (20) Adalimumab: 9 (18) MTX þ HCQ: 1 (20) Certolizumab: 0 LEF: 1 (20) Limited to cutaneous disease, n (%) 3 (60) 29 (58) Systemic events that meet ACR or SLICC classification criteria for SLE, n (%) 1 (20) 7 (14) Pulmonary involvement, n (%) 0 4 (8) Renal involvement, n (%) 1 (20) 5 (10) Pericardial involvement, n (%) 0 2 (4) Neurological involvement, n (%) 0 2 (4) *P < 0.05. Fully adjusted model by propensity score (deciles of propensity) consisting of age, gender, DAS for28 joints, disease duration, HAQ, steroid use, ethnicity, MTX use, smoking and comorbidities score. DIL: nbDMARD: non-biologic DMARD; IQR: interquartile range; pyrs: patient-years; SLICC: Systemic Lupus International Collaborating Clinics. i28 Tuesday 28 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

RA patients; and to assess factors influencing ADAbs and low drug d’Immuno-Rheumatologie, Montpellier University Hospital, Montpellier, levels. France, 5Department of Medicine, University of California Los Angeles, Methods: 331 patients were selected from the Biologics in RA Los Angeles, CA, 6Global Clinical Research, Bristol-Myers Squibb, Genetics and Genomics Study Syndicate prospective cohort [n ¼ 160, Princeton, NJ, USA and 7Department of Rheumatology, Leiden adalimumab (ADL); n ¼ 171, etanercept (ETA) treated]. Serum samples University Medical Center, Leiden, The Netherlands were collected at 3, 6 and 12 months post-therapy initiation. ADAb were measured using radioimmunoassay and drug levels using ELISA Background: In the Phase IIIb, randomized, double-blind, active- at 3, 6 and 12 months. Disease activity [DAS for28 joints (DAS28)] controlled AVERT study, abatacept (ABA) plus MTX and ABA scores were measured at each visit. Generalized estimating equation monotherapy induced protocol-defined DAS remission [DAS for28 (GEE), logistic regression and receiver operator characteristic (ROC) joints (DAS28)-CRP < 2.6] in 60.9% and 42.5% of patients with early curves tested the association and predictive value of ADAb and/or RA after 12 months on treatment (vs 45.2% with MTX alone); DAS- non-trough drug levels on treatment response as assessed by the defined remission was also maintained in 14.8% and 12.4% of patients change in DAS28 score between pre-treatment and 12 months post- 6 months after rapid withdrawal of all RA treatment (vs 7.8% with MTX treatment (ÁDAS28). alone). We further investigated predictors of drug-free DAS-defined Results: 835 serial samples were assessed (n ¼ 414 ADL; n ¼ 421 ETA). remission at 6 months after ABA withdrawal. Mean age: 56 13 years; 75% female; baseline DAS28 score 5.9 0.8; Methods: Patients with early RA (active synovitis in 2 joints, onset of median BMI 27.5 [interquartile range (IQR) 23.6–32.3). ADAbs to ADL were symptoms 2 years) and DAS28-CRP 3.2, who were anti-CCP2 detected in 24.8% (31/125 patients at 1 time point by 12 months) and in positive and MTX naı¨ve, were randomized to weekly SC ABA 125 mg none of the ETA patients. The presence of ADAbs was significantly plus MTX, ABA monotherapy or MTX alone for 12 months. At 12 associated with lower ADL drug levels (ADAb titres>100AU P ¼ 0.566; months, patients with DAS28-CRP < 3.2 stopped all RA treatment 0.0041; Spearman’s rho 0.66). Three month ADAb formation and low (ABA immediately and MTX and steroids tapered over 1 month). ADL levels were significant predictors of 12 month no EULAR response Coprimary endpoints were the proportion of patients with DAS-defined (EULAR) [receiver operating characteristic curve analysis, area under remission at month 12 and at both months 12 and 18 for ABA plus MTX curve (AUC) 0.71, 95% CI 0.57, 0.85]. Patients who developed ADAbs versus MTX alone. To assess predictive characteristics of drug-free received lower median concomitant MTX doses (15 mg/week [IQR 10–20]) DAS-defined remission, post hoc analyses were performed in all and had longer disease duration (14.0 years [6.7–19.4]) vs patients who did treatment groups: descriptive analysis of the proportion of patients not (20 mg/week [15–20] P ¼ 0.01); (7.7 years [3.6–16.0] P ¼ 0.03). ADL with DAS-defined remission at both months 12 and 18 by baseline drug level was the most significant independent predictor of ÁDAS28 at all characteristic subgroups; and clinical variables were tested individu- time points after adjusting for confounders (regression coefficient (RC) ally by logistic regression in a univariate analysis and variables with 0.060 (CI 0.015, 0.10), P ¼ 0.009). ETA levels were associated with 12 P < 0.20 were entered into a multivariate model. month EULAR response [RC 0.088 (CI 0.019, 0.16) P ¼ 0.012], although Results: Descriptive analysis showed that in both ABA treatment arms, not significant after adjustment. Significant predictors of low drug levels in the proportion of patients with a DAS28-CRP of < 2.6 at both months 12 the fully adjusted GEE model were ADAb status, BMI and adherence and 18 was numerically higher in patients with lower baseline DAS28- (Table 1). Patients with a BMI30 had significantly lower drug levels CRP, lower baseline HAQ-disability index and shorter symptom duration; compared with those with a BMI < 30 in both ADL and ETA cohorts [RC these factors were not associated with remission at months 12 and 18 in 0.78 (95% CI 0.37, 1.18) P < 0.0001]. the MTX-alone group). Predictive factors for a DAS28-CRP of < 2.6 at Conclusion: At 3 months, ADAb formation and low ADL drug levels both months 12 and 18 identified in the univariate analysis are shown in are significant predictors for poor treatment response at 12 months. Table 1. In the multivariate model, adjusted for corticosteroid use and ADAb levels, BMI and adherence are important factors influencing restricted to patients with DAS28-CRP < 2.6 at month 12, baseline drug levels in non-responding anti-TNF treated patients. DAS28-CRP [odds ratio (OR) 1.676 (95% CI 1.176, 2.387), P ¼ 0.0043] Disclosure statement: M.J. has received honoraria from UCB and and duration of remission in the first 12 months while on treatment (OR Pfizer. H.C. has received honoraria from AbbVie, Roche, Janssen, 0.913 [0.807, 1.033], P ¼ 0.1484) were identified as predictors of DA28 MSD, Pfizer, UCB, Celgene and Servier. R.B.W. has received grants/ (CRP) < 2.6 at both months 12 and 18. research support from AbbVie, Pfizer, Janssen and Novartis. C.E.M.G. Conclusion: A small but significant number of patients treated with has received grants/research support from AbbVie, Amgen, Celgene, abatacept plus MTX achieved drug-free remission 6 months after drug Eli-Lilly, GSK, Janssen, Lilly, MSD, Novartis, Pfizer and Sandoz. withdrawal. According to descriptive and multivariate analyses, less AK.L.H. has received honoraria from AbbVie and Pfizer. A.B. has severe disease activity at baseline and longer duration in DAS-defined received grants/research support from Pfizer, AbbVie, Eli-Lilly and remission on treatment were predictors for drug-free remission Sanofi-Aventis. All other authors have declared no conflicts of interest. following abatacept withdrawal. Funding: This study was supported by Bristol-Myers Squibb. Disclosure statement: P.E. has received consulting fees from AbbVie, O11 TABLE 1. Predictors of low drug levels in ADL- and ETA-treated patients using Bristol-Myers Squibb, Merck, Pfizer, Roche and Takeda; and has GEE for binary outcomesa received grants/research support from AbbVie, Bristol-Myers Squibb, Variable Regression P value Merck, Pfizer and Roche. G.R.B. has received consulting fees from coefficient (95% CI) AbbVie, Bristol-Myers Squibb, MSD, Medimmune, Novartis, Pfizer, Age 0.0056 (0.20, 0.031) 0.67 Roche, Sandoz and UCB; is a member of the speakers’ bureaus for Gender 0.054 (0.58, 0.69) 0.87 AbbVie, Bristol-Myers Squibb, MSD, Pfizer, Roche, Sandoz and UCB; BMI 0.055 (0.017, 0.094) 0.005* and has received grants/research support from AbbVie, Pfizer, Roche, Baseline disease activity 0.15 (0.21, 0.50) 0.43 UCB. V.P.B. has received grants/research support from Amgen, (DAS28-CRP score) Pfizer, Bristol-Myers Squibb, Janssen, UCB and Roche/Genentech. MTX use –0.15(0.67, 0.38) 0.59 b B.G.C. is a member of the speakers’ bureaus for Bristol-Myers Squibb, Anti-drug antibody status 1.27 (0.44, 2.07) 0.003* Merck, Pfizer, Roche-Chugai and UCB; and has received grants/ Adherence –0.68 (1.29 to 0.07) 0.028* research support from Pfizer and Roche-Chugai. D.E.F. has received aLow ADL drug level defined as level < 5 mg/ml level; low ETA drug level defined as consulting fees from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, b level < 3.62 mg/ml as per calculated concentration-effect curves; adalimumab Cytori, Janssen, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, patients only. *P < 0.05. ADL: adalimumab; DAS28: DAS for28 joints; ETA: etanercept; GEE: generalized estimating equation.

O12 TABLE 1. Predictors of DAS28-CRP < 2.6 at months 12 and 18 identified by univariate analysis O12. PREDICTORS OF DRUG-FREE REMISSION Variable OR 95% CI P-value FOLLOWING TREATMENT WITH ABATACEPT (IN COMBINATION WITH METHOTREXATE OR AS Baseline DAS 1.957 1.424, 2.689 <0.001 Baseline HAQ 1.929 1.106, 3.363 0.0206 MONOTHERAPY) IN EARLY RHEUMATOID ARTHRITIS Baseline CDAI 1.050 1.023, 1.078 0.0002 Paul Emery1, Gerd R. Burmester2, Vivian P. Bykerk3, Bernard Baseline TJC28 1.087 1.033, 1.143 0.0012 Baseline SJC28 1.115 1.051, 1.183 0.0003 G. Combe4, Daniel E. Furst5, Chetan S. Karyekar6, Dennis A. Wong6 7 Symptom duration, years 2.001 0.898, 4.459 0.0898 and Tom W. J. Huizinga Baseline pain 1.028 1.011, 1.046 0.0014 1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, Baseline erosion 1.077 0.966, 1.164 0.0616 University of Leeds, Leeds, UK, 2Department of Rheumatology and Baseline synovitis 1.070 0.977, 1.171 0.1460 Clinical Immunology, Charite´ – University Medicine Berlin, Berlin, Baseline osteitis 1.043 0.979, 1.111 0.1956 3 Germany, Department of Rheumatology, Hospital for Special Surgery, CDAI: Crohn’s Disease Activity Index; DAS28: DAS for28 joints; SJC28: swollen Weill Cornell Medical College, New York, NY, USA, 4Service joint count for 28 joints; TJC28: tender joint count for 28 joints. BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS Tuesday 28 April 2015 i29

Roche/Genentech and UCB; is a member of the speakers’ bureaus for Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, UCB and Eli Lilly; is a AbbVie, Actelion and UCB; and has received grants/research support member of the speakers’ bureaus for Abbott Laboratories, Biotest AG, from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Gilead, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, Pfizer Inc, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech and UCB. Roche, sanofi-aventis and Schering-Plough; has received grants/ C.S.K. is an employee of Bristol-Myers Squibb. D.A.W. is an employee research support from the EU and the Dutch Arthritis Foundation; and and shareholder of Bristol-Myers Squibb. T.W.J.H. has received has non-remunerative positions of influence such as officer, board consulting fees from Abbott Laboratories, Biotest AG, Bristol-Myers member, trustee or public spokesperson for Meteor Board, Abbott Squibb, Crescendo Bioscience, Novartis Pharmaceuticals Corporation, Laboratories and Roche. i30 Wednesday 29 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

Background: Patients with SLE have endothelial dysfunction CONNECTIVE TISSUE DISEASES and increased risk of cardiovascular disease (CVD). Endothelium- dependent dilatation (ED) is abnormal in lupus patients. Endothelial repair mechanisms are also impaired in SLE. Myeloid angiogenic cells (MACs) promote angiogenesis to restore damaged vessels. Vitamin D deficiency is associated with CVD in the general population. Vitamin D O13. B LYMPHOCYTE STIMULATOR PROMOTES may be a novel therapy to improve endothelial repair and function. MONOCYTE DYSFUNCTION IN SLE Methods: Vitamin D deficient (25(OH)D3 < 20 ng/ml) SLE patients were Eoghan M. McCarthy1,2, Joan Ni Gabhann2, Siobhan Smith2, treated with cholecalciferol by their physician. Replete lupus patients Suzanne Donnelly3, Grainne Kearns1 and Caroline Jefferies2 (>30 ng/ml) and healthy controls (>20 ng/ml) were also recruited. 1Rheumatology, Beaumont Hospital, 2Molecular and Cellular Endothelial function was determined by the ratio of ED to endothelium- Therapeutics, Royal College of Surgeons in Ireland and independent dilatation (EI) at baseline and after 3 months. MACs from 3Rheumatology, Mater Misericordiae University Hospital, Dublin, SLE patients were obtained from peripheral blood and cultured Ireland 10 nM calcitriol for 7 days. Function was determined by migration and angiogenesis assays. Endothelial nitric oxide synthase (eNOS) Background: SLE involves complex interactions between the innate expression (transcript and protein) was studied in human aortic and adaptive immune systems. Monocytes play a key role in the endothelial cells (HAoECs) treated with TNF-a and MAC-conditioned dysregulated immune response seen in SLE, whilst more recently B medium. lymphocyte stimulator (BLyS) has been demonstrated to play a key Results: We studied 22 deficient and 18 replete patients. Vitamin D role in SLE pathogenesis. The effect of BLyS on monocyte function in deficient patients had an increased number of MACs compared with health and SLE is poorly understood. The aim of this study was to controls (P ¼ 0.04) but impaired migratory capacity (P < 0.01) and a investigate the effect of BLyS on monocyte signalling and activation in trend toward reduced angiogenic capacity (P ¼ 0.13). Medium from healthy controls and to determine its role in the pathogenesis of SLE. calcitriol-treated MACs significantly increased angiogenesis compared Methods: Signalling pathways following BLyS stimulation were with untreated MACs (P ¼ 0.01). Vitamin D reduced IP-10 expression investigated by western blotting in monocytes from healthy controls by MACs (P < 0.001) and blockade of IP-10 restored the angiogenic and SLE patients. Quantitative PCR was conducted to investigate pro- capacity of lupus MACs in our model. In vitamin D-treated patients, inflammatory gene expression. Monocyte supernatant and serum change in 25(OH)D3 strongly correlated with change in ED/EI levels of proinflammatory cytokines were measured by ELISA. CD14þ (r ¼ 0.650, P < 0.01). This remained associated after adjustment for monocyte activation was assessed by flow cytometry. age [odds ratio 1.12 (1.02, 1.24), P ¼ 0.02]. There were no changes in Results: Following stimulation with BLyS an increase in phosphory- traditional cardiovascular risk factors or disease activity over this lated levels of STAT1, AKT, p42/44 MAPK and p38 MAPK was period. Compared to untreated SLE MACs, medium from calcitriol- observed in healthy controls indicating BLyS signals via a number of treated MACs more strongly attenuated TNF-a-mediated downregula- pathways in monocytes. A corresponding decrease in total IkB levels tion of eNOS in HAoECs (P ¼ 0.01). was observed. Strikingly, SLE patients exhibited significantly Conclusion: In this experimental study, vitamin D improved endothe- enhanced responses to BLyS stimulation compared with controls for lial function in clinically stable SLE patients. This was associated with the phospho-p42/44 MAPK, AKT and STAT pathways. Quantitative an increase in MAC number and function. The improved angiogenic PCR analysis revealed significant increases in BLyS itself, IL-6 and capacity in MACs may be mediated via downregulation of the anti- IFN-g gene expression in SLE patients following stimulation, a finding angiogenic cytokine IP-10. In addition, changes in ED/EI may be that was not replicated in controls. Subsequent ELISA confirmed mediated by MAC regulation of eNOS in endothelial cells. Vitamin D is significantly enhanced IL-6 production in the supernatant of SLE a novel therapy to reduce CVD in this patient group. patient monocytes compared with controls following BLyS stimulation. Disclosure statement: The authors have declared no conflicts of Furthermore the SLE patients exhibited significantly higher levels of interest. IL-6 in their serum. With respect to monocyte activation SLE patients expressed significantly more CD80, CD86 and HLA-DR in the resting O15. RESPONSE TO RITUXIMAB IN PATIENTS WITH state compared with healthy controls. Despite this baseline hyper- REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): activated state, BLyS stimulation resulted in significant increases in RESULTS FROM A NATIONAL MULTI-CENTRE REGISTER CD80, CD86 and MHC class II in SLE patients. By contrast, the healthy control volunteers failed to significantly upregulate any of the surface Emily J. Sutton1, Kath D. Watson1, David A. Isenberg2, markers following BLyS stimulation, indicating that SLE patients Anisur Rahman3, David Jayne4, Caroline Gordon5, Ben Parker1, monocytes are more responsive to the effects of BLyS. Interestingly, David D’Cruz6, Munther Khamashta7, Pamela Lutalo8, SLE patients with evidence of immunological activity (dsDNA positive/ Peter Lanyon9, Benjamin Rhodes10, Bridget Griffiths11, Edward low C3/C4) exhibited enhanced HLA-DR and CD86 expression M. Vital12, Chee-Seng Yee13, Christopher Edwards14, following BLyS stimulation compared with patients without evidence Mohammed Akil15, Nicola Erb16, Athiveer Prabu17, Asad Zoma18, of such activity. Finally co-culture of BLyS treated monocytes with T Neil McHugh McHugh19, Hazem Youssef20, Lee-Suan Teh21, lymphocytes resulted in enhanced expression of the T cell activation Michael W. Beresford22 and Ian N. Bruce1 marker CD69 on both CD8 and CD4þ T Cells, a finding that was 1Centre for Musculoskeletal Research, University of Manchester, significant in SLE patients. Manchester, 2Centre for Rheumatology, 3Centre for Rheumatology Conclusion: BLyS promotes dysregulation of monocyte activation and Research, University College London, London, 4Vasculitis and Lupus signalling pathways in SLE with consequential excess production of Clinic, Addenbrookes Hospital, Cambridge, 5Rheumatology pro-inflammatory cytokines and enhanced T cell activation. Research Group, University of Birmingham, Birmingham, 6Louise Disclosure statement: The authors have declared no conflicts of Coote Lupus Unit, Guy’s and St Thomas’ Hospital, 7Lupus Research interest. Unit, The Rayne Institute, St Thomas’ Hospital, 8King’s College London School of Medicine, Guy’s and St Thomas’ Hospital, London, 9Department of Rheumatology, Nottingham University Hospitals NHS O14. VITAMIN D IMPROVES ENDOTHELIAL FUNCTION AND Trust, Nottingham, 10Rheumatology, Queen Elizabeth Hospital, ENDOTHELIAL REPAIR IN SYSTEMIC LUPUS Birmingham, 11Rheumatology, Freeman Hospital, Newcastle upon ERYTHEMATOSUS Tyne, 12NIHR-Leeds Musculoskeletal Biomedical Research Unit and John A. Reynolds1, David W. Ray2, Terence O’Neill1, M Yvonne Leeds Institute of Rheumatic and Musculoskeletal Medicine, Alexander3 and Ian N. Bruce1,4 University of Leeds, Leeds, 13Department of Rheumatology, 1Arthritis Research UK Centre for Epidemiology, Institute of Doncaster and Bassetlaw Hospitals NHS Foundation Trust, Inflammation and Repair, 2Endocrinology Research Group, Institute Doncaster, 14NIHR Wellcome Trust Clinical Research Facility, of Human Development, University of Manchester, 3School of University Hospital Southampton NHS Foundation Trust, Healthcare Sciences, Manchester Metropolitan University and 4NIHR Manchester, 15Rheumatology Department, Royal Hallamshire Manchester Musculoskeletal Biomedical Research Unit, University of Hospital, Sheffield, 16Rheumatology, Russell’s Hall Hospital, Dudley, Manchester, Manchester, UK 17Department of Rheumatology, Worcester Acute Hospitals NHS BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS Wednesday 29 April 2015 i31

Trust, Worcester, 18Rheumatology, Hairmyres Hospital, East Kilbride, beginning to flare by 6 months post therapy. Further analysis will 19Rheumatology, Royal National Hospital for Rheumatic Diseases, attempt to identify predictors of response in this cohort. Bath, 20Department of Rheumatology, Aberdeen Royal Infirmary, Disclosure statement: E.J.S. has received funding for research from Aberdeen, 21Department of Rheumatology, Royal Blackburn Roche and GSK. C.G. has received consulting fees from Genentech, Hospital, Blackburn and 22Institute of Translational Medicine (Child GSK, MedImmune, Merck Serono, Parexel, Roche, and UCB Pharma; Health), University of Liverpool, Liverpool, UK and remuneration for lectures from GSK and UCB as well. All other authors have declared no conflicts of interest. Background: Published efficacy data for rituximab in SLE are complex with positive single-centre case series and negative randomized O16. HEAT SHOCK PROTEIN 70 PROTECTS AGAINST ER controlled trials. This may be due to heterogeneity of SLE or the STRESS-INDUCED MITOCHONDRIAL DYSFUNCTION; A populations, study design or endpoints of trials. The BILAG Biologic POTENTIAL THERAPEUTIC TARGET TO REDUCE MUSCLE Registry (BILAG BR) is a national, multicentre, prospective study which WEAKNESS IN IIM? aims to determine the safety and efficacy of biologics in SLE patients refractory to standard immunosuppressive therapy. The objective of Adam P. Lightfoot1, Malcolm J. Jackson1, Anne McArdle1 and the present analysis is to describe clinical response to rituximab at 3 Robert G. Cooper1 and 6 months post therapy. 1Musculoskeletal Biology, University of Liverpool, Liverpool, UK Methods: Patients with SLE (4 ACR 1997 criteria), 5 years old, refractory to conventional therapy and newly starting treatment with Background: The idiopathic inflammatory myopathies (IIMs) are a rituximab, from centres across the UK, were recruited into the BILAG group of acquired autoimmune diseases which primarily target skeletal BR. A comprehensive questionnaire collected information on con- muscle. Patients typically present with symmetrical proximal muscle comitant medications, risk factors for infection, co-morbidities and weakness and elevated circulating levels of muscle enzymes, such as SLE disease duration. Disease activity was measured using the BILAG creatine kinase. Classical anti-inflammatory therapies are successful in 2004 Index and the SLEDAI 2000 (SLEDAI-2K) at treatment initiation suppressing the inflammation within the muscle; but most patients and at 3 and 6 months post therapy. remain weak. Moreover, recent research indicates that weakness may Results: Baseline and 3- and 6-month disease activity were collected actually precede inflammatory cell infiltrations in murine IIM. Research for 80 patients (92.5% women) starting therapy with rituximab. The has further demonstrated that activation of the endoplasmic reticulum cohort included 44 (60.3%) white British patients. The median (ER) stress response in IIM patients may be associated with muscle (interquartile range [IQR]) age and disease duration at baseline were weakness. In other cell types there is a well-established link between 39.5 years (IQR 30.0–47.3) and 5.7 years (IQR 2.5–11.6) respectively. ER stress and augmented mitochondrial function, and mediated by the The most commonly involved BILAG 2004 index systems were generation of reactive oxygen species (ROS). Furthermore, significant mucocutaneous [33 (41.25%)], renal [28 (35.0%)] and musculoskeletal evidence suggests that ROS play a key role in muscle dysfunction in [25 (31.0%)]. The baseline SLEDAI-2K was 8 (IQR 4–13.5). At 3 months range of muscle pathologies other than IIM, such as in ageing. follow-up, 47 (58.75%) patients showed an improvement in their Protection against muscle dysfunction during ageing has been overall BILAG 2004 index, 16 (20.0%) had persisting active disease achieved by pharmacological and transgenic up-regulation of mole- and 12 (15.0%) had deteriorating disease. The majority of patients [11/ cular chaperones, such as heat shock protein 70 (HSP70). We have 12 (91.7%)] who deteriorated, did so in one system only. In the same here interrogated the hypothesis that, in IIM, activation of ER stress follow-up period, 56 (70.0%) had an improved SLEDAI-2K, 15 pathways can induce changes in mitochondrial function which may (18.75%) had no change and 9 (11.25%) worsened. Data at 6 induce muscle weakness which could be ameliorated by up-regulation months showed 39 (48.75%) with improvement, 18 (22.5%) with of HSP70. persistent disease and 16 (20.0%) with deterioration. In addition, there Methods: C2C12 myotubes were grown in culture and treated with the was a trend towards steroid dose being reduced over the 6-month ER stress-inducing compound tunicamycin in the absence or period (Table 1). presence of the HSP upregulating drug 17AAG. ER stress pathway Conclusion: There was variability in the degree of response to activation, antioxidant enzyme network activation and HSP70 upre- rituximab with respect to both the magnitude and duration of gulation were determined by quantitative PCR and sodium dodecyl response, in this cohort of SLE patients refractory to standard sulfate polyacrylamide gel electrophoresis/western blotting. immunosuppression. Although nearly half of the cohort demonstrated Mitochondrial function was analysed using a Clark electrode. significant reduction in disease activity across all systems at 6 months, Results: C2C12 myotubes treated with tunicamycin displayed activa- there was a sub-group that worsened in either the original system tion of the ER stress pathway via upregulation of the key ER stress involved, or developed activity in a new system. This may be explained markers Grp78, Grp94 and splicing of X-box binding protein 1 (XBP-1). by some patients who initially responded to rituximab at 3 months, Furthermore, ER stress pathway activation caused declines in

O15 TABLE 1. Baseline and follow-up data Variable (n ¼ 80 unless otherwise stated) Value, n (%) or median (IQR) Baseline characteristics Female 74 (92.5) Ethnicity (N ¼ 73) White British/other white 44 (60.3) Indian/Pakistani/Bangladeshi 10 (13.7) African ancestry 10 (13.7) Mixed (white/Caribbean/other mixed) 9 (12.3) BILAG 2004 Index score at baseline 1 A score and/or 2 B score 55 (68.8) Age at diagnosis, years 30.0 (18.4–40.2) Age at baseline, years 39.5 (30.0–47.3) Disease duration at baseline, years 5.7 (2.5–11.6) Prednisolone dose at baseline, mg/day (n ¼ 70) 10 (8.0–22.5) Number of previous immunosuppressant therapies at baseline (n ¼ 78) 2 (1–3) Baseline SLEDAI-2K score 8 (4–13.5) Baseline SLICC/ACR Damage Index (n ¼ 64) 0 (0–1) Patient follow-up BILAG 2004 Index 3 months, n (%) 6 months, n (%) Improvement [all As to B/C/D; all Bs to C/D (allowing for 1B persisting)] 47 (58.75) 39 (48.75) Persistent active disease (any system still A or 2Bs as per previous time point) 16 (20.0) 18 (22.5) Deterioration (any system to A from B/C/D or to B from C/D) 12 (15.0) 16 (20.0) No change/inactive (stable C/D/E with no new A or B) 5 (6.25) 7 (8.75) SLEDAI-2K (n ¼ 80) 3 months 6 months Score at follow-up, median (IQR) 4 (2–6.5) 4 (2–7) Improve, n (%) 56 (70.0) 56 (70.0) Persist, n (%) 15 (18.75 13 (16.25) Worsen, n (%) 9 (11.25) 11 (13.75) Prednisolone dose at follow-up, median (IQR) , mg/day 10 (5–13.75) 8.5 (5–12.5) IQR: interquartile range; SLEDAI-2K: SLEDAI 2000; SLICC: Systemic Lupus International Collaborating Clinics. i32 Wednesday 29 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

mitochondrial function, as evidenced by reduced respiratory control employee of Genentech. H.S. is an employee of Roche. J.S. is an ratio (RCR), phosphate oxygen ratio (P:O) and the rate of ATP employee of Genentech. D.E.F. has acted as a consultant for Abbott, synthesis, which was prevented by 17AAG. These changes were Actelion, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor, determined as mediated by phosphorylation of JNK, which was CORRONNA, Genentech, Gilead, GlaxoSmithKline, National Institutes upregulated in response to ER stress induction and attenuated by of Health, Novartis, Pfizer and Roche; has acted as a consultant for 17AAG. USB; has received honoraria from Abbott, Actelion, BMS, Genentech, Conclusion: These data suggest that ER stress pathway activation Encysive and UCB; is a member of the speakers’ bureaus for Abbott alters muscle mitochondrial bioenergetics, thus attenuating oxygen and Genentech; and has received research grants from Actelion, BMS, consumption and ATP generation, i.e. creating an energy deficit. As Celgene, Genentech, Gilead, NIH, Novartis, Roche and UCB. All other HSP70 seems to protect against such adverse changes, drugs authors have declared no conflicts of interest. targeting chaperone expression (e.g. arimoclomol) may represent a therapeutic avenue worthwhile for alleviating a component of IIM- O18. EARLY HALO SIGN FEATURES ON ULTRASOUND induced muscle weakness. EXAMINATION OF TREATED PATIENTS WITH GIANT CELL Disclosure statement: The authors have declared no conflicts of ARTERITIS interest. Ana S. Serafim1, Surjeet Singh1, Jennifer Piper1, Andrew Hutchings2, 3 1 4 O17. SAFETY AND EFFICACY OF SUBCUTANEOUS Mike Bradburn , Cristina Ponte , Bhaskar Dasgupta , Wolfgang Schmidt5, Eugene McNally1, Andreas Diamantopoulos6 TOCILIZUMAB IN ADULTS WITH SYSTEMIC SCLEROSIS: 1 WEEK 24 DATA FROM A PHASE II/II TRIAL and Raashid Luqmani 1Nuffield Department of Orthopaedics, Rheumatology and Christopher P. Denton1, Dinesh Khanna2, Jaap M. van Laar3, Musculoskeletal Sciences, University of Oxford, Oxford, 2London Angelika Jahreis4, Sabrina Cheng4, Helen Spotswood5, School of Hygiene and , London School of Hygiene Jeffrey Siegel4 and Daniel E. Furst6 and Tropical Medicine, London, 3University of Sheffield, Sheffield, 1Rheumatology Department, University College London Medical 4Department of Rheumatology, Southend University Hospital, School, London, UK, 2Department of Internal Medicine, University of Westcliff-on-Sea, UK, 5Department of Rheumatology, Hospitals - Michigan, Ann Arbor, MI, USA, 3Rheumatology Department, Berlin-Buch, Berlin-Buch, Germany and 6Department of University Medical Center Utrecht, Utrecht, The Netherlands, Rheumatology, Hospital of Southern Norway, Kristiansand, Norway 4Medical Department, Genentech, South San Francisco, CA, USA, 5Medical Department, Roche Products Ltd, Welwyn Garden City, Background: The Temporal Artery Biopsy vs US in diagnosis of GCA UK and 6UCLA Medical Center, University of California, Los Angeles, (TABUL) study compared temporal artery US with biopsy for CA, USA diagnosing GCA. All patients with newly suspected GCA underwent a single US scan of temporal and axillary arteries, followed by a biopsy Background: SSc is a progressive, debilitating disease with limited of the symptomatic temporal artery within 7 days of starting steroids. treatment options. IL-6 is implicated in disease pathogenesis, and the To determine the potential role of US as a biomarker in GCA, we serum level may predict worsening lung fibrosis. Tocilizumab (TCZ), an measured differences in the size of the halo around the arteries with IL-6 receptor inhibitor, is under evaluation in the ongoing 2-year, phase different duration of steroid therapy; furthermore we correlated halo II randomized, controlled trial, faSScinate. Week-24 efficacy and safety size with ischaemic symptoms of GCA. data are presented. Methods: We included 415 cases with suspected GCA. We analysed Methods: Patients (18 years) with active diffuse SSc (5-year data from 301/415 patients with clinically defined definite or probable disease duration, mRSS 15–40 units, elevated acute-phase reactants) GCA at baseline. Using the IBM SPSS Statistics package version 20, were randomized 1:1 to s.c. TCZ 162 mg or placebo (PBO) weekly for we performed a cross-sectional analysis with linear and logistic 48 weeks. The primary endpoint was mean change in mRSS from regression models to determine the relationship between halo size and baseline (BL) at week 24. Change in the HAQ-disability index was a days of steroid treatment and also with ischaemic symptoms of GCA secondary endpoint. Patient and lung responses were secondary/ (jaw and tongue claudication, amaurosis fugax and reduced, lost or exploratory measures. double vision). Results: BL characteristics for the 87patients (43 TCZ, 44 PBO) were Results: We studied 214 women and 87 men [mean (S.D.) age 72.6 similar, including mean (S.D.) mRSS [TCZ 26.4 (7.2); PBO 25.6 (5.9)]. At (9.3) and 71.6 (9.6) years, respectively] from 20 different recruitment 24 weeks, a numerically favourable effect of TCZ over PBO on mRSS centres. Fifty per cent were scanned on or before day 2 of steroid was noted (TCZ –3.9, PBO, 1.2; Table 1). A greater proportion of TCZ treatment. Forty-three per cent (131 patients) had a halo in one or more patients achieved clinically meaningful reduction in mRSS of 4.7 temporal segments, 48.5% (146 patients) had bilateral temporal artery [TCZ 43.2% (16/37), PBO 26.3% (10/38); P ¼ 0.15]. More PBO than halos and 12.6% (38 patients) had axillary involvement. The linear TCZ patients (81% vs 50%) had worsening of forced vital capacity regression model showed a consistently smaller halo size over the 7 (FVC) change (0%) and 27% of PBO patients vs 3% of TCZ patients days of steroid treatment (P < 0.005) for temporal arteries. The had 10% FVC decline (P ¼ 0.009). Adverse events (AEs)/serious AEs likelihood of finding a halo diminished with time, until day 4 of steroid were reported in 88.4%/20.9% TCZ and 90.9%/25.0% PBO patients. treatment (P < 0.005). At least one ischaemic symptom was present in There were fewer non-infectious SAEs in TCZ (5 patients) vs PBO (10 42% of the patients: jaw claudication in 48.2% (146 patients), reduced patients) patients. Infection/infestation SAEs were more common in or lost vision in 36.6% (111 patients), double vision in 8.6% (26 TCZ patients (6 patients vs 1 pt). SAEs (by system organ class), patients), tongue claudication in 6.6% (20 patients) and amaurosis potentially indicative of SSc complications, reported more frequently in fugax in 4% (12 patients). Jaw claudication occurred more frequently PBO patients: cardiac (TCZ 0 patients, PBO 3 patients), gastrointest- in patients with a halo (P < 0.05). Temporal artery symptoms correlated inal (TCZ 0 patients, PBO 2 patients) and renal (TCZ 0 patients, PBO 2 with ipsilateral US findings (P < 0.05). patients). Three TCZ and two PBO patients discontinued the drugs due Conclusion: In newly diagnosed GCA, US halo size decreases rapidly to AEs. One death occurred in each arm: pulmonary infection in a TCZ with steroid treatment and correlates with the presence of ischaemic pt (day 109) and heart failure in a PBO pt 131 days after withdrawal. symptoms, supporting its early use as a diagnostic and potentially Conclusion: Favourable trends in skin and lung score for TCZ were prognostic marker. In future we will be exploring the potential value of detected though the primary endpoint was not met. Encouraging change in halo size in individual patients over time to determine its changes in FVC were noted. The study is ongoing (double-blind and value in monitoring response to treatment. open-label phases). Disclosure statement: R.L. has received consulting fees from GSK, Disclosure statement: C.P.D. has acted as a consultant for Actelion Novartis, Roche and Pfizer. All other authors have declared no Pharmaceuticals US. A.J. is an employee of Genentech. S.C. is an conflicts of interest.

O17 TABLE 1. Change from baseline in mRSS, HAQ-DI and FVC at week 24 (ITT population) TCZ PBO Difference (95% CI) P a mRSS, adjusted , mean (S.D.) 3.9 (n ¼ 41) 1.2 (n ¼ 43) 2.70 (5.85, 0.45) 0.09 a HAQ-DI, adjusted , mean (S.D.) 0.14 (n ¼ 41) 0.12 (n ¼ 42) 0.02 (0.19, 0.23) 0.85 FVC (L) change 0%, n (%) 15 (50.0; n ¼ 30) 30 (81.1; n ¼ 37) FVC (L) decline 10%, n (%) 1 (3.3; n ¼ 30) 10 (27.0; n ¼ 37) 0.009 aMixed-model repeated measures analysis that included treatment, visit, joint involvement at baseline, treatment-by-visit interaction, baseline parameter and baseline parameter-by-visit interaction. HAQ-DI, HAQ-disability index; ITT: intent-to-treat; mRSS, modified Rodnan skin score; PBO: placebo; TCZ: tocilizumab. i33 Wednesday 29 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

Background: Enthesitis is a clinical hallmark of spondyloarthropathy IMAGING (SpA), and historically conventional US has been utilized to detect inflammatory changes such as tendon thickening, calcification and hypoechogenicity with loss of tendon fibrillar structure. Sonoelastography (SE) is a novel US application that quantifies the tissue elasticity (i.e. the degree of tissue stiffness) within an anatomical O19. A DIAGNOSTIC PROTOCOL FOR GIANT CELL structure. It provides different biomechanical tissue information that ARTERITIS USING ULTRASOUND ASSESSMENT can complement changes that are detected by grey-scale US (GSUS)

1 1 1 1 and power Doppler US (PDUS). The aim of this pilot study was to Jennifer Piper , Ana S. Serafim , Cristina Ponte , Surjeet Singh , compare SE to GSUS and PDUS in the assessment of enthesitis. Bhaskar Dasgupta2, Wolfgang A. Schmidt3, Eugene McNally1, 4 5 Methods: A total of 40 entheseal sites of patients with SpA were Andreas Diamantopoulos , Andrew Hutchings and included in the analysis. Bilateral proximal plantar fascia, distal Achilles Raashid Luqmani1 1 2 tendon, distal and proximal patellar tendon insertion and distal NDORMS, University Of Oxford, Oxford, Department of quadriceps tendon were systematically scanned with the same Rheumatology, Southend University Hospital, Southend on Sea, UK, 3 Aplio-400 Diagnostic US System (Toshiba Medical Systems Rheumatology Berlin-Buch, Immanuel Krankenhaus Berlin, Berlin- Corporation; multi-frequency transducer 7–18 Hz) in GSUS, PDUS 4 Buch, Germany, Department of Rheumatology, Hospital of Southern and real-time sonoelastography imaging mode. SE grading was based 5 Norway, Kristiansand, Norway and London School of Hygiene and on differential tissue stiffness: blue-green (hard), 0; green-yellow Tropical Medicine, London, UK (intermediate), 1; yellow-red (soft), 2; and red (very soft), 3. GSUS and PDUS were graded based on the validated Madrid Sonographic Background: US has yet to supersede temporal artery biopsy as the Enthesis Index (MASEI) scoring system (i.e. calcification, power gold standard diagnostic test for confirmation of GCA. This may reflect Doppler enhancement, erosions, tendon structure, tendon thickness poor consistency of the scanning technique, due to the lack of a and bursa was scored on a semiquantitative scale of 0–3). The standardized US protocol. We have developed a standardized sensitivity and specificity of SE, GSUS and PDUS were compared with protocol which was implemented in a prospective study of 857 clinical examination as the reference standard. participants: 439 healthy age match controls and 418 participants with Results: SE grading strongly correlated with PDUS grading suspected GCA [Temporal Artery Biopsy vs US in diagnosis of GCA (rS ¼ 0.852, P < 0.01), and combined GSUS/PDUS gradings [TABUL]). Each participant was assessed for typical US features of (rS ¼ 0.716, P < 0.01). The sensitivity of SE and combined GSUS/ GCA: presence of a halo (oedema in the vessel wall), stenosis or PDUS were identical when compared with the reference standard; occlusion of the vessel. 71.4%. In contrast the specificity of SE was 63.2% and combined Methods: A detailed scanning protocol was developed for all GSUS/PDUS was 26.3%, when compared with the reference participants and healthy controls. Recording the presence or absence standard. of US features of GCA in each segment of the temporal and axillary Conclusion: This is the first study to compare SE with conventional arteries. Sonographers were asked to acquire video and static images US for the detection of enthesitis in SpA. SE had a greater specificity for each participant. The sonographer measured and documented: compared with conventional US and a comparable sensitivity in the halo diameter and length; pulse Doppler measurements prior to and detection of enthesitis in SpA. SE is a promising new imaging within a stenosis and arterial occlusion. Each sonographer was biomarker in SpA; further work is required to standardize the grading required to be proficient in the protocol by scanning at least 10 system and image acquisition for SE. healthy controls (evaluated by US experts), passing an online test Disclosure statement: The authors have declared no conflicts of showing normal and abnormal scans (pass mark >75%) and scanning interest. a patient with US evidence of active GCA. Results: The US scanning protocol was started by 33 sites, with only 22 sites completing the training in 6.7 months (range 0.2–16.4 months). O21. ULTRASOUND-DEFINED TENOSYNOVITIS IMPROVES A total of 439 controls were scanned across 31 sites (one sonographer THE PREDICTION OF EARLY RHEUMATOID ARTHRITIS covered three sites). The online test was passed by 39 sonographers 1 1 1 1 (multiple sonographers at some sites) with an average of 2 attempts Ilfita Sahbudin , Luke Pickup , Paola de Pablo , Jason Bell , 1 2 3 4 (range 1–4); 22 sonographers successfully scanned an active GCA Zaeem Cader , Abhishek Abhishek , Gina Allen , Peter Nightingale , 2 2 2 patient, validated by the expert panel. The longest delay in training was Alison Jordan , Paresh Jobanputra , Simon Bowman , 1 1 1 locating a patient with active GCA. We have created a bank of 857 sets Christopher Buckley , Karim Raza and Andrew Filer 1 of recorded images of temporal and axillary arteries from 418 patients Rheumatology Research Group, School of Infection and Immunity, 2 with suspected GCA and 439 healthy controls. Expert review of the University of Birmingham, Department of Rheumatology, University 3 first 279 scans revealed expert agreement in 91% of cases, Hospitals Birmingham NHS Foundation Trust, Birmingham, Green demonstrating the robustness of the technique and training package. Templeton College, University of Oxford, Oxford and 4Wolfson Conclusion: Quality and accuracy are imperative for the clinical use of Computer Laboratory, University Hospitals Birmingham NHS US in diagnosis of GCA. The development of an effective protocol, Foundation Trust, Birmingham, UK including training, ensures consistency and proficiency in scanning. The methodology can be extended for evaluation of additional artery Background: Early identification of patients at risk of RA is essential assessment, including carotid, subclavian and vertebral arteries, to allow prompt institution of therapy which has been shown to extending the value of a structured approach. We recommend the improve outcomes. Current early diagnostic strategies for RA TABUL study scanning protocol as the standard approach for include the 2010 ACR/EULAR criteria and the Leiden rule, which diagnosis of GCA using US. rely heavily on clinical assessment. Identifying factors that can Disclosure statement: R.L. has received consulting fees from GSK, further improve the discriminative ability of such clinical tools is an Roche, Novartis and Pfizer. All other authors have declared no important goal. US scanning is a sensitive and specific modality for conflicts of interest. the detection of subclinical disease including tenosynovitis, which is a common manifestation of early RA. We aimed to establish the prevalence of tenosynovitis assessed by US in an unselected very O20. SONOELASTOGRAPHY AS A NOVEL IMAGING early arthritis cohort; and explore whether the presence of BIOMARKER IN SPONDYLOARTHROPATHY: A PILOT STUDY tenosynovitis improves the prediction of RA compared with the validated Leiden score. Ilfita Sahbudin1, Luke Pickup1, Caroline Cardy2, Adrian Peall3 and Methods: 107 patients with clinically apparent synovitis of at least one Andrew Filer1 joint and symptom duration 3 months underwent clinical and tendon 1Rheumatology Research Group, MRC Centre for Immune US assessments and were followed prospectively for 18 months, Regulation, School of Immunity and Infection, University of determining outcome by 1987 ACR criteria. A blinded systematic US Birmingham, 2Rheumatology Department, Worcestershire Acute assessment determined the presence of grey scale and power Doppler Hospitals NHS Trust, Birmingham and 3Rheumatology Department, tenosynovitis at 16 tendon regions involving bilateral fingers (extensor Wye Valley NHS Trust, Birmingham, UK and flexor compartments), wrists (extensor and flexor compartments), i34 Wednesday 29 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

shoulders (bicep tendon) ankles (anterior compartment, peroneals and differences (95% CI) were 9.5 (6.5, 12.4) mm and 1.7 (1.8, 5.2) mm. posterior tibialis tendon) using a Siemens Acuson Antares scanner Estimates of intra and inter-rater reliability were 0.88 and 0.56 for (Siemens, Bracknell, UK) and multifrequency (5–13MHz) linear array providing at least one vessel measurement in an evaluation of a given transducer. image. Intra and inter-rater reliability estimates for vessel width were Results: 43 patients developed RA [very early RA (VERA)], 20 patients 0.91 and 0.85, respectively; by disease (SSc/PRP/HC), these figures developed non-RA persistent disease (NRAP) and 44 patients had were 0.97/0.66/0.53 and 0.69/0.55/0.32, respectively. resolving disease at follow-up. A total of 1712 tendon regions in 107 Conclusion: Mean vessel width was unmeasurable in a sizable patients were included in the analysis. All patient groups had evidence minority (24%) of image evaluations with potential implications for of tenosynovitis at one or more tendon compartment during baseline the representativeness of this measure. Measurement of larger vessels assessment (VERA 86%, NRAP 75%, resolving 70%). There were may be more reliable, and this may account for the higher reliability in significant differences in the distribution of tendon involvement SSc. Research on the impact of training on rater reliability, and into between the three groups including the extensor carpi ulnaris (ECU) more objective (automated) analysis methods is required to further tendon (VERA 54%, NRAP 15%, resolving 18%; P < 0.001) and hand develop this promising outcome measure. flexor tendon compartments (VERA 54%, NRAP 40%, resolving 11%, Funding: This study was supported by the Raynaud’s & Scleroderma P < 0.001). The area under the curve (AUC) for the Leiden score as a Association (MU3). continuous variable was 0.860. Logistic Regression analysis demon- Disclosure statement: The authors have declared no conflicts of strated that hand tenosynovitis (TS), hand flexor TS and ECU TS all interest. improved AUC values for the prediction of RA (hand TS AUC ¼ 0.878, P ¼ 0.035; hand flexor TS AUC ¼ 0.884, P ¼ 0.019, wrist ECU TS O23. VERTEBRAL ENDPLATE OR MODIC CHANGE IS AN AUC ¼ 0.872, P ¼ 0.054). INDEPENDENT RISK FACTOR FOR EPISODES OF SEVERE Conclusion: This is the first study to show that US scanning-defined AND DISABLING LOW BACK PAIN TS contributes additional predictive information over and above the Leiden score. Hand flexor and extensor scanning provides the optimal Juhani Maatta1,2, Sam Wadge1, Alex J. MacGregor1, minimal US data to improve predictive model. Jaro Karppinen2 and Frances M. Williams1 Disclosure statement: The authors have declared no conflicts of 1Twin Research, King’s College London, London, UK and 2Medical interest. Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland O22. RELIABILITY AND VALIDITY OF MEAN VESSEL WIDTH IN CAPILLAROSCOPY FOR EVALUATING SYSTEMIC Background: Modic change (MC) describes vertebral endplate and SCLEROSIS-RELATED MICROANGIOPATHY bone marrow lesions visible by MRI. MC has been associated with both disc degeneration (DD) and with lower back pain (LBP). It remains Graham Dinsdale1,2, Tonia Moore1,3, Joanne Manning3, unclear whether MC causes LBP independently or through association Andrea Murray1,2, Michael Berks4, Philip Tresadern4, with DD, a well-recognized cause of LBP. Moreover, association of MC Christopher Taylor4, Neil O’Leary5, Christopher Roberts5, with episodes of severe, disabling LBP is uncertain. This is of particular John Allen6, Marina Anderson7, Maurizio Cutolo8, interest because severe episodes may lead to time of work and Roger Hesselstrand9, Kevin Howell10, Paula Pyrkotsch7, ultimately contribute to unemployment. The objective of the present Francesca Ravera8, Vanessa Smith11, Alberto Sulli8, Marie Wildt9 study was to assess the relationship between MC and severe, and Ariane Herrick1,3 disabling LBP, features of intervertebral DD and incident MC during 1Centre for Musculoskeletal Research, University of Manchester, 10-year follow-up among a sample of the British population (TwinsUK). 2Photon Science Institute, University of Manchester, Manchester, Methods: Volunteers were recruited from the TwinsUK register to the 3Directorate of Rheumatology, Salford Royal Hospital NHS Foundation Spine study comprising MRI and interview for data collection between Trust, Salford, 4Centre for Imaging Sciences, Institute of Population 1996 and 2000, with a subset attending for follow-up a decade later. Health, 5Centre for Biostatistics, Institute of Population Health, MC, DD (evaluated by loss of disc height and signal intensity, presence University of Manchester, Manchester, 6Regional Medical Physics of disc bulge and anterior osteophytes) and Schmorl’s nodes (SN) Department, Freeman Hospital, Newcastle upon Tyne, 7Institute of were determined on T2-weighted lumbar MR scans. Ageing and Chronic Disease, University of Liverpool, Liverpool, UK, Results: Complete data were available for 823 subjects at baseline 8Research Laboratory and Academic Division of Clinical Rheumatology, and 429 at follow-up. Mean age at baseline was 54.0 years (range 32– Dept. Internal Medicine, University of Genova, Genova, Italy, 70), with 96% females. The prevalence of MC was 32.2% at baseline 9Department of Clinical Sciences, Section of Rheumatology, Lund and 48.7% at follow up. Subjects with MC were older (P < 0.001) and University, Lund, Sweden, 10Institute of Immunity and Transplantation, more overweight (by BMI; P ¼ 0.026). At baseline (and follow-up), more Royal Free Campus, University College London, London, UK, subjects reporting severe LBP demonstrated MC (35.0% vs 16.4%, 11Rheumatology, Ghent University Hospital, Ghent, Belgium respectively, P < 0.001; 35.1% vs 20.0%, respectively, P < 0.001). In multivariable analyses, MC was associated with episodes of severe, Background: The characteristic microvascular structural abnormalities disabling LBP [odds ratio 1.58 (95% CI 1.04, 2.41)] independently of of SSc are easily viewed and recorded at the nailfold using high- age, BMI, DD and SN at baseline. Loss of disc height and disc signal magnification videocapillaroscopy. Image annotation software allows intensity was independently associated with prevalent MC at baseline, both qualitative and quantitative assessment of the capillaries, and the and disc height and disc bulge with incident MC during follow up. potential for tracking changes over time. Our objective was to assess the Conclusion: A number of studies have shown the association reliability and validity of mean capillary width (known to be increased in between MC and low back pain, but this is the first to highlight the SSc) as an example of one of a number of measured parameters. independent relationship, despite co-existing DD. MC is an indepen- Methods: 124 patients [102 with SSc, 22 with primary RP (PRP)] and 50 dent risk factor for episodes of severe and disabling LBP in middle- healthy controls (HCs) underwent high-magnification videocapillaro- aged women. Our results give insight into the more precise factors of scopy imaging of all 10 digits (1740 images). All patients signed DD affecting development of MC, in particular the role of disc height informed consent. Image subsets, sampled over disease categories, loss as part of degeneration. These observations support further work were randomly allocated to at least 2 of 10 capillaroscopy experts. aimed at identifying the precise histology underlying MC. These raters used custom software to assess images. To assess intra- Disclosure statement: The authors have declared no conflicts of rater reliability, each rater performed repeat evaluations on an image interest. subgroup. At least six images were assessed from each subject. Raters identified distal vessel locations in an image, and then were asked to O24. THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN measure the apical width of each identified vessel. We examined the THE STRATIFICATION OF SLE: A MULTICENTRE CROSS- probability of raters identifying at least one distal vessel in an image SECTIONAL STUDY (logistic mixed-effects model); and the mean distal vessel width (per image evaluation), conditional on an image evaluation having at least Ahmed S. Zayat1, Christopher J. Edwards2, Md Yuzaiful Md Yusof1, one distal vessel apex measured (linear mixed-effects model). Sandeep Mukherjee2, Richard J. Wakefield1, Paul Emery1 and Results: 3478 images were evaluated. Each rater assessed a median Edward M. Vital1 (range) of 112 (87–1401) unique images from 14 (9174) subjects. 1Leeds Institute of Rheumatic and Musculoskeletal Medicine Same-rater repeat evaluations were performed on (median) 16% of (LIRMM), University of Leeds, Leeds and 2NIHR Wellcome Trust images, and 904 images from 116 patients were evaluated by at least Clinical Research Facility, University Hospital Southampton NHS two raters. Raters measured at least one distal vessel width in 76% of Foundation Trust, Southampton, UK image evaluations (74% SSc, 81% PRP, 75% HC). The mean vessel width in HC was 11.8 mm and mean vessel width was higher in SSc Background: Musculoskeletal symptoms in SLE are common and (21.2 mm) but not significantly different in PRP (13.4 mm); respective cause substantial morbidity. However, assessing the nature of these BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS Wednesday 29 April 2015 i35

symptoms can be challenging. Multiple recent studies have reported experiences and views of support for the psychological impact of positive musculoskeletal US findings in SLE patients with joints inflammatory arthritis. symptoms. However, the severity of such abnormalities and their Methods: A questionnaire designed by researchers, patient partners relationship to the clinical condition are poorly understood. The and clinicians included three open-ended questions asking about objectives of this study were to determine the characteristics and examples of helpful and unhelpful psychological support. severity of musculoskeletal US abnormalities in SLE and to correlate Questionnaires were administered to 1080 patients at six regional these abnormalities with the clinical condition. rheumatology units across England, and 1200 members of a national Methods: Patients fulfilling the ACR diagnostic criteria for SLE were patient charity. They were completed anonymously and returned included in Leeds and Southampton. Patients had hand US examina- directly to the research team. tion (including joints and tendon sheaths) and clinical assessment Results: 1210 (53%) patients completed the questionnaire, with 779 including BILAG, SLEDAI, tender joint count (TJC) and swollen joint (64%) responding to the open-ended questions [80% female; mean count (SJC). Patient had and immunology assessment. age (S.D.) 59 years (12.6); patient global 5 (2.2); disease duration < 5 Any patient who had rhupus (RF or CCP positive) was excluded. years (40%), 5–10 (20%), >10 (40%)]. Data were analysed using a Results: A total of 55 patients were recruited. Among them, 18%, hybrid approach. Inductive analysis of the full data set led to the 18%, 55% and 9% of patients were BILAG A, B, C and D respectively. development of a coding framework which guided a deductive In those with inflammatory joint symptoms (BILAG A–C), 58.3% had analysis of data subsets. Three main themes emerged: significant US finding [grey-scale US (GSUS) 2 and/or power Doppler Psychological consequences, including the impact of symptoms US (PDUS) 1]. All BILAG A had moderate–severe PD (i.e.PD 2). (Pain and fatigue have a huge impact), loss (One loses confidence, However, a substantial number of patients who had BILAG B were the ability to commit to anything, and it can completely change one’s judged not to have significant US findings. By contrast, many patients personality), negative emotions (I have so much anger due to my with BILAG C did have significant US abnormality (Table 1). Erosions arthritis and frustration), depression (Since I was first diagnosed I have were found in about one third of BILAG A patients. Tenosynovitis was experienced bouts of depression and found it much harder to cope) also found in a significant number of BILAG A–C patients (Table 1). and isolation (It’s a very lonely illness); barriers to support, including 16% of patients had synovitis on US but no swollen joints. There was a poor communication (Not returning phone calls when in need of moderate positive correlation between presence of PD and presence reassurance or information makes you feel alone and panicked), lack of erosions [correlation coefficient (CC) 0.44, P ¼ 0.001]. There was a of time (I didn’t feel I could speak to rheumatology nurse/consultant strong positive correlation between US synovitis and SJC (CC 0.72 about my problems as it was always rushed/lacking time), a medical and 0.82, P < 0.001) for GS and PD, respectively). However, there was focus (When emotional problems are mentioned in the Rheumatology a weak correlation between US synovitis and TJC (CC 0.031 and 0.23, Department they tend to be ignored, concentrating more on physical P ¼ 0.85 and 0.168 for GS and PD, respectively). There was moderate wellbeing) and being someone who cannot ask for help (I find it hard to correlation between US synovitis and SLEDAI (CC 0.29 and 0.42, ask for help with anything physical or emotional); and facilitators of P ¼ 0.002 and 0.033 for GS and PD, respectively). Neither inflamma- support, including the opportunity to talk to people with arthritis (It’s tory markers nor SLE immunological markers (i.e. ANA, ENA, reassuring to know you’re not the only one), access to services (A complements and immunoglobulins) appeared to be associated with counsellor who specifically worked with patients managing chronic joint inflammation. disease helped me through those dark days) and understanding from Conclusion: US appears to have value in the assessment and clinicians (I was very emotional and did not understand what was stratification of musculoskeletal symptoms in SLE. US was able to happening to me, they [rheumatology team] made me aware that these detect clinically significant synovitis in patients who had BILAG C or had things were my new illness and it was normal for RA). no swollen joints. In addition, a substantial number of patients with clinical Conclusion: High levels of psychological distress were commonplace synovitis were judged not to have significant US findings. There was a and often attributed to fatigue and pain. Patients looked to the moderate positive association between PD and joints erosions. US may rheumatology team to acknowledge the psychological impact of their bemoresensitiveandprovetobeabetter classification tool than clinical inflammatory arthritis and identified their understanding as helpful. examination and BILAG in assessment of joint pathology in SLE. Further research will address the training needs of rheumatology Disclosure statement: E.M.V. has received consulting fees from GSK; teams to meet patients’ support needs. has received honoraria from Roche and Chugai; and has received Funding: This study was supported by Arthritis Research UK (grant grants/research support from Roche. All other authors have declared number 19755). no conflicts of interest. Disclosure statement: All authors have declared no conflicts of interest.

O24 TABLE 1. Frequencies of different US abnormalities in different BILAG groups O26. THE RELATIONSHIP BETWEEN PAIN SEVERITY AND US abnormality A (n ¼ 10) B (n ¼ 10) C (n ¼ 30) D (n ¼ 5) ALLOSTATIC LOAD: RESULTS FROM THE ENGLISH GS 2 and/or PD 1, % 100 80 38 0 LONGITUDINAL STUDY OF AGEING PD 1, % 100 80 20 0 PD 2, % 100 40 7 0 Ross Wilkie1, Kimberly Sibille2, Diane Smith1 and John McBeth1 Erosions, % 33 20 7 0 1Arthritis Research UK Primary Care Centre, Keele University, Keele, Tenosynovitis, % 45 30 11 0 UK and 2Department of Aging and Geriatric Research, University of GS: grey-scale; PD: power Doppler. Florida, Gainesville, FL, USA

Background: Musculoskeletal pain is stressful and may impact on a number of physiological systems (e.g. inflammatory, metabolic, cardiovascular, neuroendocrine). When these physiologic systems are persistently or extensively challenged without adequate recovery, they can begin to show signs of wear and tear and demonstrate BHPR patterns of dysregulation or allostatic load (AL). AL indices are theoretically based, empirically supported and predict functional decline, comorbidity and mortality. This study tested the hypothesis that increasing pain severity was associated with increasing AL; O25. PATIENT EXPERIENCES OF PSYCHOLOGICAL determined whether this association was independent of lifestyle and SUPPORT IN INFLAMMATORY ARTHRITIS: OPEN-ENDED comorbidities; and identified individual biomarkers associated with RESPONSES IN A NATIONAL SURVEY pain severity. Methods: Data was used from a population-based prospective cohort Emma Dures1, Isobel Fraser2, Alice Peterson3, Judy Caesley3, study of adults aged 50 years; the English Longitudinal Study of Celia Almeida1, Marianne Morris1, Nicholas Ambler4, Jon Pollock2 Ageing (ELSA) wave 4 (conducted in 2008; n ¼ 5341). Pain severity was and Sarah Hewlett1 measured using two variables: often troubled with pain (yes/no); and if 1Nursing & Midwifery, University of the West of England, Bristol, ‘yes’, the intensity of pain (mild/moderate/severe). Twelve biomarkers 2Health & Social Sciences, University of the West of England, of AL were used to create an index: systolic blood pressure, diastolic 3Academic Rheumatology, University Hospitals Bristol and 4Pain blood pressure, mean arterial pressure, resting pulse rate, fibrinogen, Management, North Bristol NHS Trust, Bristol, UK high density lipoprotein (HDL), low density lipoprotein (LDL), CRP, glycosylated haemoglobin (HbA1C), dehydroepiandrosterone Background: Psychological support can improve quality of life and (DHEAS), insulin-like growth factor-1 (IGF-1) and waist-hip ratio self-management, and is recommended in UK, European and (WHR). Participants with a high clinical risk (lowest quartile for HDL, American treatment guidelines. This study examined patient IGF-1, DHEAS and the highest quartile for all other measures) were i36 Wednesday 29 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

scored 1. AL total scores ranged from 0 to 12, with higher scores on-going support and therapeutic alliance as targets for future trials of indicating higher AL. Linear regression was used to examine the exercise in older adults with knee pain. association between pain severity and AL, initially adjusting for Disclosure statement: The authors have declared no conflicts of interest. putative confounders (age, gender, education) and then for lifestyle (smoking, alcohol, activity levels) and comorbidities (depression, O28. WE ALL KEEP SCHTUM: THE EXPERIENCES AND cardiovascular disease, respiratory disease, cancer, diabetes and COPING STYLES OF MEN WITH RHEUMATOID ARTHRITIS arthritis). Results were expressed as unstandardized b-coefficients with 95% CIs. Logistic regression was used to examine the Caroline A. Flurey1, Sarah Hewlett1, Alan White2, Karen Rodham3, association between pain severity and high clinical risk of allostatic Robert Noddings4 and John Kirwan5 load for each of the 12 biomarkers adjusting for confounders. 1Faculty of Health and Applied Sciences, University of the West of Results: The mean age of participants was 65.3 (S.D. 9.2) years, 55% England, Bristol, 2Centre for Men’s Health, Institute of Health and were female and 62.4% had no pain, 12.6% mild pain, 19.1% Wellbeing, Leeds Beckett University, Leeds, 3Psychology, Sport and moderate pain and 5.9% severe pain. The mean AL score was 3.2 Exercise, Staffordshire University, Stoke-on-Trent, 4Rheumatology, (S.D. 2.0). AL was associated with mild (0.08; 0.00, 0.16), moderate University Hospitals Bristol NHS Trust and 5Academic (0.15; 0.08, 0.22) and severe pain (0.38; 0.27, 0.49) following Rheumatology, University of Bristol, Bristol, UK adjustment for confounders. Only severe pain (0.24; 0.11, 0.36) was associated with AL when lifestyle and comorbidities were included in Background: Current research in RA reflects the preponderance of the model. Seven biomarkers were associated with pain severity; women with the condition (30% male). Research in other conditions fibrinogen, HDL, CRP, HBA1c, DHEAS, IGF-1 and WHR. Systolic suggests men and women have different coping styles and support blood pressure, diastolic blood pressure, resting pulse, and mean needs. The aim of this research was to explore the experiences and arterial pulse were not associated with pain severity. coping styles of men with RA. Conclusion: Findings indicate a dose response relationship between Methods: Six focus groups with men with RA and five follow-up musculoskeletal pain and allostatic load and that there may be a interviews to explore their experiences of RA, coping mechanisms and specific allostatic load signature for pain that differs from other health ideas for effective support. These data were analysed using Inductive conditions. Thematic Analysis. Disclosure statement: The authors have declared no conflicts of interest. Results: 22 male patients were included, with a mean age of 64years, disease duration of 9years and HAQ of 1.24. Three overarching themes are proposed. The first is: treat it as a death – experiencing loss. These O27. UPTAKE AND MAINTENANCE OF PHYSIOTHERAPY- men discussed loss in many areas of their lives due to RA including: LED EXERCISE AND GENERAL PHYSICAL ACTIVITY IN strength (‘These radiators I have to lift up are so heavy. Years ago I’d OLDER ADULTS WITH KNEE PAIN: THE BEEP LONGITUDINAL just sling them on my shoulder and walk about, not anymore’), QUALITATIVE STUDY independence (‘It’s soul destroying because it takes away your Clare Jinks1, Andrew Moore2, Melanie A. Holden1 and Nadine independence. Yeah, your dignity. Financially you lose your indepen- E. Foster1 dence...you stop and think now [before spending money]’), and 1Research Institute for Primary Care & Health Sciences, University of masculine identity (‘A man is happier working, he’s the head of the Keele, Keele and 2Musculoskeletal Research Unit, University of home when he’s a family man’). The second is: we all keep schtum – Bristol, Bristol, UK ways of coping. Many of the men coped by keeping going despite their RA (‘It’s just there isn’t it, you’ve got to get on with it’), but some took Background: This study investigated participants’ experiences of this too far (‘I had to go to work and I was crying in pain’) and others physiotherapy-led exercise interventions in the BEEP randomized trial used exercise as self-punishment (‘I just run and run until I can’t run (ISRCTN93634563). Participants were randomized to usual care (UC), anymore...I just feel like punishing myself’). Some of these men were with up to four treatment sessions of advice and exercise over 12 able to talk to their wives or partners if they needed support, but weeks; Individually Tailored Exercise (ITE), an individualized, super- generally preferred not to talk to friends (‘They’re [friends] not vised and progressed lower-limb exercise programme in 6–8 treat- understanding at all, that’s why we all keep schtum’). Asking for help ment sessions over 12 weeks; or Targeted Exercise Adherence (TEA), was avoided as it was seen as not a very macho thing and RA was supporting the transition from lower limb exercise to general physical kept hidden in public (‘You obviously just have to put on a brave face activity in 8–10 treatment contacts over 6 months. Views of the because it really hurts’). The third is: we’d end up just moaning—what acceptability of each intervention, impact on exercise and general support would men like? In general these men were not interested in a physical activity behaviour and explanations for change in exercise support group (‘Speaking to other people with the same complaint, I behaviour were evaluated. can’t see what good it would do’), but would consider an information Methods: Face to face interviews with participants in each of the session (‘Something in relation to what research has been done’). treatment arms at two time-points (n ¼ 30 on completion of Conclusion: It is important to men to retain their masculine identity physiotherapy treatment, n ¼ 22 interviewed 12–18 months later). A and roles. As in other conditions, these male patients seem to be layered approach to analysis was undertaken blind to the trial clinical employing coping strategies not addressed by current interventions, results. Analysis included open coding (using constant comparison) of which can sometimes be destructive. Thus, they may have different transcripts to investigate experiences of interventions, views on support needs to women. This needs further exploration, as under- exercise and barriers and facilitators to exercise; deductive coding standing the potentially different needs of men is necessary to improve to predetermined codes of individualization, supervision and progres- communication and inform the design of interventions. sion (three core characteristics of BEEP interventions); and within-case Disclosure statement: C.A.F. has received an Arthritis Research UK and cross-case longitudinal analysis focusing on change. Fellowship. All other authors have declared no conflicts of interest. Results: Different levels (basic and higher) of supervision, progression and individualization emerged that matched the protocols for each O29. A MULTI-CENTRE SURVEY OF TOLERABILITY AND treatment arm. Overall higher levels were contained in narratives of ADHERENCE FOR PATIENTS ON REGULAR METHOTREXATE participants in TEA and ITE. Key themes of therapeutic alliance and 1 2 3 3 change in knowledge emerged as facilitating factors across all three Sandra Robinson , Una Martin , Sarah Gibson , Emmanuel George , 4 4 5 arms of the trial. These were linked to physiotherapist and patient Matthew Kalinowski , Peter Prowse , Ade Adebajo , 6 6 1 7 factors and appeared to foster improved knowledge and maintenance David Marshall , Michael Reed , Peta Heslop , Hilary Wrightson 8 of exercise in the long-term. Time and place were also important and David Walker 1 facilitating factors across the three arms of the trial. Patient factors (e.g Research and Development, Northumbria Healthcare NHS 2 continuing to have knee pain or being pain-free, self-efficacy and fear Foundation Trust, Tyne and Wear, UK, Rheumatology, Waterford of doing the wrong thing or falling, lack of motivation, impact of Regional Hospital, Waterford, Ireland, 3Rheumatology, Wirral University comorbidities) were barriers across all three arms at both time points. Teaching Hospital NHS Foundation Trust, Wirral, 4Rheumatology, Time and place (e.g. lack of access to facilities, no time) were barriers Hampshire Hospitals NHS Foundation Trust, Hampshire, across all arms at both time points except at follow up in UC. Lack of 5Rheumatology, Sheffield University, Sheffield, 6Rheumatology, monitoring or support (e.g. from a physiotherapist or family member) Inverclyde Royal Hospital, Inverclyde, 7Rheumatology, Northumbria was highlighted as a barrier in the long term. More regular reviews or Healthcare NHS Foundation Trust, Tyne and Wear and 8Rheumatology, monitoring were suggested as ways to improve BEEP interventions. Freeman Hospital, Newcastle upon Tyne, UK Conclusion: Interview participants experienced different levels of supervision, individualization and progression. Similar barriers and Background: MTX has become the core DMARD for the treatment of facilitators to exercise and physical activity existed across the three RA. It has also found utility in treating other forms of inflammatory arms of the trial and barriers remained at follow-up. These findings arthritis including PsA, and can be used to reduce corticosteroid help to contextualize the clinical results of the trial. They also highlight therapy. We were struck by the number of patients who complain of BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS Wednesday 29 April 2015 i37

side effects that interfere with their lives but are not sufficiently serious comparable countries in confronting consequences of long-term to need withdrawal. We surveyed our own patients and found that diseases. One potentially effective approach is by educating people 57% had at least 1 side effect. We were interested to see if this pattern to become more health literate. Early life interventions relating to was repeated in other places in the UK and to determine whether exercise and good MSK health practices may be an effective addition patients reported side effects and adherence differently to doctors and to traditional approaches. LifeLab is a science-based approach to nurses. improving teenagers’ health-related attitudes and behaviour. The Methods: A steering group of participants was organized to reflect a LifeLab approach was developed at the University of Southampton wide geographical spread throughout the UK and included nurses and and combines educationalists, scientists, clinical researchers and consultants. The questionnaire was modified to include questions school children and has been effective in improving young peoples’ about adherence. 50 consecutive patients on MTX for any reason, who understanding of the nature of diseases and reasoning about health were on a stable dose and planning to continue, were surveyed from issues. However, no specific MSK health education components have each site. This added six centres and 300 patients. previously been included in LifeLab. Results: The rate of any side effect was higher in all of the new centres Methods: In 2014 the first MSK LifeLab workshop was designed than our first survey ranging between 67% and 86%. Fatigue with educationalists and researchers in biomechanics, occupational presented the highest difference from the first survey; visual analogue therapy, podiatry and physiotherapy from the MSK Research Cluster scale (VAS) scores for severity were 35 % higher in other centres. All at Southampton for year 8 (age 12–13 years) school students. The other side effects rated 20% higher than the original survey. workshops aimed to promote young peoples’ health literacy in Adherence was explored with questions about choosing not to take musculoskeletal health and integrated experiential learning using 3D and forgetting to take. Choosing not to take ranged from 2% to 8%, motion analysis, real-time US scanning of muscles contracting; with high VAS scores for severity of side effects which suggests that radiographs of normal and OA foot joints; anatomy models and the decision to choose not to take MTX was related to severity of side hand and hip joint implants. The workshops covered the impact of effects. Patient response to forgetting to take MTX showed more OA joint disease on daily life; capturing and illustrating joint variation, ranging from 0 to 18% and they rated lower VAS scores for movement using state of the art 3D motion analysis technology; severity of side effects. It is interesting to note that the survey and an in-depth look at muscles using US imaging. Learning completed by the nurse produced the highest disclosure of non- objectives included students being able to identify key components adherence by the patients; this may reflect on the way nurses of active healthy living for bones, muscles and joints; observe communicate with patients. Numbers of missed weeks ranged patterns in how healthy joints can move and contrast patterns with between 2 and 4. injured joint movement; discover what role muscles play in healthy Conclusion: These surveys have shown a very high rate of side effects joints; and compare healthy joint structures with arthritic joint that patients are prepared to put up with for the benefits they get from structures. MTX. The main variation is in the complaint of Fatigue which is very Results: 58 students from three state secondary schools, attended a subjective. The variation in admission of non-adherence is interesting university widening participation outreach day within which the MSK and merits further study as it may be an underestimate. LifeLab workshop was run. On the same day the students also Disclosure statement: The authors have declared no conflicts of attended workshops in Humanities and Oceanography. When asked interest. which workshop of the outreach day was their favourite 43% of the students identified the MSK workshops. Feedback on why the workshops were enjoyable included: ‘I enjoyed biomechanics O30. RAISING TEENAGERS’ AWARENESS OF because I like looking at how things work and move; Ostioarphritus. MUSCULOSKELETAL HEALTH THROUGH LIFELAB: A I’m into sports & find the body interesting; The bones because you COLLABORATION BETWEEN SCHOOL STUDENTS, got to find out about the body. The interactive nature of the TEACHERS AND CLINICAL ACADEMIC RESEARCHERS. workshop with teenagers having hands on learning was also well received: My favourite was bones because they made it fun; and Jo Adams1, Kath Woods Townsend2, Marcus Grace3, 1 1 1 1 The bones experiments because the technology involved was Martin Warner , Cathy Bowen , Peter McQueen , Charlotte Dando awesome.’ and Maria Stokes1 1 2 Conclusion: Using interactive MSK workshops as part of Faculty of Health Sciences, University of Southampton, National LifeLab presents an exciting health literacy approach to Institute of Health Research Southampton Biomedical Research 3 encourage young people to start to engage in understanding Centre, University of Southampton and Southampton Education their MSK health. School, University of Southampton, Southampton, UK Disclosure statement: The authors have declared no conflicts of interest. Background: Musculoskeletal (MSK) disease is the major cause of years lived with disability in the UK. The UK is behind other i38 Wednesday 29 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

sample size and acceptability to inform a future, multicentre, appropriately powered randomized controlled trial (RCT). PRIMARY CARE Methods: This study was randomized, controlled and took place in an urban location. Volunteer paramedics attended training sessions about osteoporosis, falls and fracture risk calculation. Patients aged 50 years who fell and were attended by a paramedic and medically O31. GOUT AND RISK OF SUBSEQUENT VASCULAR EVENT: stabilized were eligible. They (or their consultee) were asked for verbal A DISCRETE-TIME EVENT HISTORY ANALYSIS IN THE consent to answer questions relating to their fracture risk and for a CLINICAL PRACTICE RESEARCH DATALINK researcher to later contact them. Those who subsequently formally consented were randomized to intervention (investigation and/or Lorna E. Clarson1, Samantha L. Hider1, John Belcher1, treatment advice based on the patients FRAX calculation was sent Edward Roddy1, Carl Heneghan2 and Christian D. Mallen1 to the patient’s GP and the patient asked to attend their doctor), or 1Research Institute for Primary Care & Health Sciences, Keele control (usual care). Target recruitment was 50/group. Qualitative University, Keele and 2Department of Primary Care Health Sciences, techniques assessed the acceptability of the intervention to patients, Oxford University, Oxford, UK their GPs and attending paramedics. Results: 25 trained paramedics gathered verbal consent from 175/ Background: Current evidence suggests that gout is an independent 1447 (12.1%) of patients who fell between June 2013 and 2014. 53/ risk factor for excess cardiovascular morbidity and mortality; yet, 175 (30%) who expressed interest then proceeded to formal study suboptimal care for patients with gout in primary care persists. We participation. The average age was 81 years (range 57–98) and 27/53 aimed to identify risk factors specific to these gout patients which may (51%) women. 23/53 (43%) of patients reported prior fracture. The contribute to their increased risk of vascular disease. median number of falls reported in the previous 12 months was 3.0 Methods: Discrete-time event history analysis was used to estimate and median risk of hip fracture 7.6% [risk >5% in 37/53(70%)]. 28/53 the contemporaneous effect of changing vascular risk factors on the (53%) patients were judged to be at intermediate/high risk of fracture risk of an incident vascular event (cardiovascular, cerebrovascular or (National Osteoporosis Guideline Group treatment thresholds). Of the peripheral vascular) in each year following diagnosis of gout for 8386 28 patients at intermediate/high risk of fracture, only 9 had ever taken primary care gout patients over the age of 50 with no prior history of bone protection medication, and just 4 were currently doing so. Three vascular disease, using records from the Clinical Practice Research out of four patients recommended new treatment in the 3-month follow Datalink. up period were in the intervention group. Qualitative work suggested Results: Older age, higher Charlson co-morbidity score, incident the intervention was acceptable to the majority of patients, GPs and prescription of anti-platelet or lipid-lowering medications, measure- paramedics. However, some patients could not recall consent at 3- ment of blood pressure or body mass index (whether normal or high) month follow up, paramedics commented upon patient indisposition and a mean daily dose of 300 mg of allopurinol or less were associated as a barrier to recruitment, and GPs highlighted difficulties in with an increased risk of a vascular event. Female gender, incident implementing fracture prevention advice in patients with complex diagnosis of hyperlipidaemia or chronic kidney disease and increasing medical backgrounds. persistence with allopurinol (measured using the medication persis- Conclusion: The qualitative work suggests the intervention is tence ratio) all reduced the risk of a vascular event. acceptable. The calculated fracture risk among those who fall is Conclusion: The effect of some risk factors differed from those high, but few high-risk patients were taking bone protection. This previously reported using continuous survival analysis, with increased suggests an opportunity for paramedics to improve targeted fracture risk of vascular event associated with measuring blood pressure and prevention therapy in patients who fall, though relatively poor body mass index even when recorded as normal, and hyperlipidaemia recruitment rate suggests the need for an alternative RCT design. and chronic kidney disease appearing protective, perhaps demon- Disclosure statement: S.C. has received honoraria for speaking at a strating that those most at risk are those not under surveillance for meeting sponsored by Lilly. All other authors have declared no alternative reasons. This would support the introduction of a routine conflicts of interest. vascular surveillance from diagnosis of gout. Disclosure statement: The authors have declared no conflicts of interest. O33. A REAL HEADACHE: A CROSS-SECTIONAL SURVEY OF SYMPTOMS ASSOCIATED WITH GIANT CELL ARTERITIS IN A PRIMARY CARE SETTING O32. CAN PARAMEDICS USE FRAX TO IDENTIFY PATIENTS 1,2 2 3 AT GREATEST RISK OF FUTURE FRACTURE AMONG THOSE Max Yates , Karly Graham , Richard A. Watts and 2 WHO FALL? A FEASIBILITY STUDY Alex J. MacGregor 1Rheumatology, Norfolk and Norwich University Hospital, 2Norwich 1 1 2 Shane Clarke , Bethany Simmonds , Rachael Gooberman-Hill , Medical School, University of East Anglia and 3Rheumatology, 3 4 5 Maria Robinson , Rosemary Greenwood , Elsa Marques , Ipswich Hospital, Ipswich, UK Jonathan Benger6, Christopher Salisbury7, Lee Shepstone8 and 9 Rachel Bradley Background: GCA is the commonest form of large vessel vasculitis. 1Rheumatology, University Hospitals Bristol, 2School of Clinical 3 Its association with permanent visual loss in up to 23% of patients Sciences, University of Bristol, Bristol, Research and Clinical Audit, makes prompt recognition and treatment essential. However, the high South Western Ambulance Service NHS Foundation Trust, Exeter, prevalence of headache and the lack of specificity of a raised ESR (two 4 5 Research Design Service, University Hospitals Bristol, School of key items of the current classification criteria) pose a challenge to Social and Community Medicine, University of Bristol, Bristol, identify GCA appropriately in primary care. In addition, using 6 Faculty of Health and Applied Sciences, University of West of classification criteria for the purposes of diagnosis risks the mis- England, Bristol, 7Centre for Academic Primary Care, School of interpretation of inference. In this study we aimed to investigate the Social and Community Medicine, University of Bristol, Bristol, prevalence of symptoms associated with GCA in a general practice 8Norwich Medical School, University of East Anglia, Norwich and population with the objective of identifying key discriminating features 9Care of the Elderly, University Hospitals Bristol, Bristol, UK that identify the disease in this setting. Methods: A cross-sectional survey of all individuals aged 55 years or Background: As the majority of patients who fracture have fallen, it older from a large general practice of two sites in Norfolk, UK, was follows that people who fall can usefully be targeted in any programme carried out. The questionnaire was developed to include the full range to reduce osteoporotic fracture. We hypothesized that trained of clinical features that have been related to GCA, identified from a paramedics attending patients who had fallen could determine an literature review. All GP diagnoses of GCA identified on the GP individual’s 10-year fracture risk (using FRAX), and, by informing their database and clinical care records were reviewed for the purpose of general practitioner (GP) of that risk, positively influence the proportion case classification against 1990 ACR criteria. Key clinical features of patients appropriately treated (e.g. weekly alendronate) for high were identified through step-wise logistic discrimination adjusting for fracture risk. We determined that a feasibility study was required to age and sex. Likelihood ratios of individual features in the final selected explore and refine issues of study design, recruitment, retention, model were estimated. BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS Wednesday 29 April 2015 i39

O33 TABLE 1. Prevalence of individual symptoms and likelihood ratios associated with a clinical diagnosis Symptom Prevalence for whole sample (n ¼ 2277) Positive likelihood Negative likelihood ratio (95% CI) ratio (95% CI) Male, % Female, % Jaw or tongue pain 4.3 10.7 7.8 (4.0, 15.0) 0.46 (0.20, 1.09) Visual disturbance 18.2 22.0 2.54 (1.26, 5.10) 0.62 (0.31, 1.25) Headache lasting longer than 7days 2.8 6.7 14 (7.86, 25.0) 0.39 (0.16, 0.96) Scalp tenderness 4.4 11.3 13 (9.89, 16.0) 0 (0, 0.99) Early morning shoulder pain and stiffness lasting >1 h 20.6 29.7 3.54 (2.70, 4.65) 0.17 (0.03, 1.04) Unexplained weight loss 3.6 4.9 16 (8.86, 28.0) 0.39 (0.16, 0.96) Myalgia 15.6 22.5 3.35 (1.95, 5.77) 0.46 (0.19, 1.13) Migraine 14.8 23.6 1.98 (0.81, 4.87) 0.77 (0.45, 1.32)

Results: The analysis is based on completed responses from 2277 had access to a dedicated early arthritis clinic although most GPs individuals from an invited sample of 4728 individuals aged 50 years or rated ease of access to secondary care rheumatology as moderate older (response rate 49%). The median age was 68 years old. There [median NRS 7 (IQR 5–8)]. was no statistical difference between responders and non-responders Conclusion: GPs were moderately confident in recognizing early RA. for age structure and gender ratio. 15 participants self-reported a However, despite guidance recommending early referral of patients diagnosis of GCA (8 of who were confirmed on their care record). Of with suspected synovitis, most GPs would still arrange investigations the total responses, 2.8% of males and 6.7% of females reported prior to referral. This suggests that further work is needed to reduce having suffered severe headaches lasting longer than 7 days. In the avoidable diagnostic delay for this patient group. logistic discrimination model (adjusted for age and sex) the following Disclosure statement: The authors have declared no conflicts of clinical features provided the most predictive power: headache, interest. unexplained weight loss and early morning shoulder pain and stiffness (receiver operator characteristic ¼ area under curve 96.8%). Likelihood ratios for individual symptoms as predictors of GCA are displayed in O35. POPULATION PREVALENCE AND ASSOCIATIONS OF Table 1. PLANTAR HEEL PAIN IN ADULTS AGED 50 YEARS AND OVER: Conclusion: This is the first study to survey an entire population for CROSS-SECTIONAL FINDINGS FROM THE CLINICAL symptoms commonly associated with GCA in a community setting. ASSESSMENT STUDY OF THE FOOT The data show that GCA accounts for a small proportion of those with prolonged headache. As expected the co-occurrence of jaw, tongue Edward Roddy1, Rebecca Case1, Martin J. Thomas1, Hylton pain and scalp tenderness with headache are important predictors of B. Menz1,2, Trishna Rathod1 and Michelle Marshall1 GCA in this setting. It is of particular interest that the highest positive 1Research Institute for Primary Care & Health Science, Keele likelihood ratio is related to unexplained weight loss. This is not University, Keele, UK and 2Lower Extremity and Gait Studies included in current classification criteria but may be of diagnostic value Program, La Trobe University, Bundoora, Australia in identifying GCA in the in the general practice setting. Disclosure statement: The authors have declared no conflicts of Background: Plantar heel pain is a very common presentation to interest. primary care and yet among the most difficult to manage. There is a lack of epidemiological evidence on the rates of consultation for the condition and of the health status of affected individuals. Greater O34. WHEN DO GENERAL PRACTITIONERS REFER understanding of these aspects may help more appropriately target SUSPECTED RA? A NATIONWIDE GP SURVEY and successfully manage the condition. The objectives of this study were to estimate the population prevalence and distribution of plantar 1,2 1 1 Samantha L. Hider , Milica Blagojevic-Bucknall , Rebecca Case , heel pain in mid-to-older age groups; examine associations with health 1 3 3 Kris Clarkson , Rebecca Stack , Karim Raza and Christian status; and report frequency of healthcare use. 1 D. Mallen Methods: A general Health Survey was mailed to all adults aged 50 1 Arthritis Research UK Primary Care Centre, Research Institute for years registered with four general practices in North Staffordshire. Primary Care & Health Sciences, Keele University, Keele, Plantar heel pain in the last month was defined by self-reported 2 Rheumatology Department, Haywood Rheumatology Centre, shading on a foot manikin. Disabling plantar heel pain was defined as Staffordshire & Stoke-on-Trent Partnership NHS Trust, self-reported foot problems occurring on most/every day(s) on at least Stoke-on-Trent and 3Rheumatology Research Group, School of one of the 10 function items of the Manchester Foot Pain and Disability Immunity & Infection College of Medical & Dental Sciences, Index. Population prevalence was estimated using multiple imputation University of Birmingham, Birmingham, UK and weighted logistic regression. The following analyses were based on complete case data. Binary logistic regression estimated the Background: Early diagnosis of RA and prompt initiation of DMARD association between plantar heel pain and demographic character- treatment leads to improved outcomes. Diagnostic delay can be at the istics, health status measures [Short Form-12, Hospital Anxiety and level of the patient, general practitioner (GP) or secondary care. Depression Scale) and lifestyle factors (BMI), Short-Form International National Institute for Health and Care Excellence Quality Standards for Physical Activity Questionnaire, past use of high-heeled footwear]. RA suggest that patients with persistent small joint synovitis are Healthcare use was summarized as the 12-month period prevalence of referred to a rheumatology service within 3 working days of foot-related consultation. presentation. The aim of this study was to investigate GP referral Results: The population prevalence of plantar heel pain was 9.1% practice for patients with suspected RA. (95% CI 8.3, 9.9) and 7.4% (95% CI 6.7, 8.1) for disabling plantar heel Methods: 5000 GPs across England were randomly selected from the pain. Prevalence was higher in females, and in those with routine and Binley’s database and mailed a cross-sectional questionnaire that manual occupations. Plantar heel pain was less prevalent but more investigated which factors GPs rated as important when diagnosing frequently disabling in older age groups. After adjustment for age, sex RA, together with their confidence at recognizing suspected RA [on a and BMI, plantar heel pain was associated with poorer physical health 10-point numeric rating scale (NRS)]. Ethical approval for the study [adjusted odds ratio (aOR) 3.9 (95% CI 2.9, 5.2)], poorer mental health was obtained from Keele University. [aOR 2.6 (95% CI 2.0, 3.3)], anxiety [aOR, mild 2.4 (95% CI 1.8, 3.1); Results: 1388 complete questionnaires were returned. The mean (S.D.) moderate 3.0 (95% CI 2.2, 4.0); severe 3.2 (95% CI 2.2, 4.7)], age of responders was 47 (9.4) years. 705 (60%) were female and were depression [aOR, mild 2.2 (95% CI 1.7, 2.9); moderate 2.7 (95% CI 2.0, qualified as a GP for an average of 16.6 (9.7) years. Responders were 3.6); severe 3.2 (95% CI 2.2, 4.7)], BMI [aOR, overweight 1.7 (95% CI moderately confident at diagnosing RA [median (interquartile range; 1.3, 2.2); obese 2.1 (95% CI 1.5, 2.9); severely obese 5.1 (95% CI 3.6, IQR) visual analogue scale 7 (5–7) and had suspected RA in 4 (2–6) 7.2)] and low levels of physical activity [aOR, 2.9 (95% CI 2.3, 3.6)] but patients in the last 2 years. GPs rated the five most important factors in not high-heeled footwear [aOR, 0.8 (95% CI 0.6, 1.1)]. The 12-month diagnosing RA as: small joint swelling; early morning stiffness of period prevalence of foot-related consultation with a general practi- >60 min; small joint pain; high ESR and CRP; and anti-CCP antibody tioner or allied health professional was 43.6% (95% CI 38.6, 48.8) and positivity. Only 343 (24.7%) responders would refer suspected RA 41.5% (95% CI 36.6, 46.5), respectively. immediately, with 999 (71.9%) preferring to arrange tests prior to Conclusion: Plantar heel pain is a common, disabling symptom referral. Of those GPs that arrange further tests, the majority request among adults aged 50 years and over. Observed patterns of RF (1098, 79.1%) or CRP (1094, 78.8%) prior to referral and many association indicate that in addition to focused site-specific manage- (631, 45.5%) would also arrange plain radiographs. Only 498 (35.8%) ment, interventions should also target more general physical and i40 Wednesday 29 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

psychological factors that could potentially act as barriers to treatment function [Western Ontario McMaster Osteoarthritis Index (WOMAC)] at compliance and recovery. 6 months. A range of secondary outcomes were measured at baseline Disclosure statement: R.C. is funded by a National Institute for Health and at 3, 6, 9 and 18 months. Participants and physiotherapists were Research (NIHR) Research Methods Fellowship. All other authors have not blind to allocation, but outcome data collection and analyses were declared no conflicts of interest. conducted blind to allocation. Primary analysis was by intention-to- treat; sensitivity analysis was per protocol analysis. Results: 514 older adults with knee pain were randomized and 87% O36. IMPROVING THE EFFECTIVENESS OF EXERCISE provided primary outcome data at 6 months. There were no clinically THERAPY FOR OLDER ADULTS WITH KNEE PAIN: A or statistically significant differences between groups at 6 months [UC PRAGMATIC RANDOMIZED CONTROLLED TRIAL mean (S.D.) WOMAC pain 6.4 (4.0) and function 21.4 (14.1); ITE pain 6.4 Nadine E. Foster1, Elaine Nicholls1, Melanie A. Holden1, Emma (4.0) and function 22.3 (13.7); TEA pain 6.2 (3.8) and function 21.5 L. Healey1, Stephanie Tooth1 and Elaine M. Hay1 (13.2)] or at any other time point. On average, participants in all three 1Arthritis Research UK Primary Care Centre, Keele University, Keele, groups improved during treatment and the benefits of treatment were UK relatively stable over 18 months. At 6 months, according to the OMERACT-OARSI responder criteria, 50%, 51% and 55% were Background: Exercise for knee pain attributable to OA is recom- categorized as treatment responders in UC, ITE and TEA, respectively. mended as a core treatment in clinical guidelines but it is unclear how Self-reported exercise adherence was high at 3 months in all groups exercise is best delivered to optimize patient outcomes. (UC 75%, ITE 81%, TEA 81%) but remained higher for longer in the Methods: The BEEP trial (ISRCTN93634563) was a parallel, pragmatic TEA group at later time points (UC 55%, ITE 68% and TEA 77% at 6 randomized, controlled trial investigating the effectiveness of two months). Sensitivity analysis did not change the results, but there was physiotherapy-led exercise interventions compared with usual phy- a non-significant trend for better pain and function scores in those in siotherapy care (UC), for pain and function in older adults with knee the TEA group who received the intervention per protocol. No serious pain. Adults aged 45 years with knee pain attributable to OA from 65 adverse events and 16 minor and transient adverse effects were general practices in England were randomized using computer- reported. generated blocks of size 3 to UC (up to four treatment sessions of Conclusion: Changing the content and characteristics of physiother- advice and exercise over 12 weeks); Individually Tailored Exercise (ITE; apy-led exercise programmes for older adults with knee pain did not an individualized, supervised and progressed lower-limb exercise provide better outcomes compared with usual physiotherapy care. programme in 6–8 treatment sessions over 12 weeks); or Targeted Funding: This study was supported by the NIHR (NIHR-RP-011–015). Exercise Adherence (TEA; supporting the transition from lower limb Disclosure statement: N.E.F. is supported by an NIHR Research exercise to general physical activity in 8–10 treatment contacts over 6 Professorship. M.A.H. was part-funded by the NIHR School for months). 47 physiotherapists from 5 National Health Service phy- Primary Care Research. E.L.H. was part funded by the NIHR siotherapy services delivered treatment: 15 delivered UC, 17 ITE and Collaborations for Leadership in Applied Health Research and Care 15 TEA. Primary outcomes were self-reported pain and physical West Midlands. All other authors have declared no conflicts of interest. i41 Thursday 30 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

O38. METHOTREXATE INDUCES EPIGENETIC MODIFICATION OF THE FOXP3 LOCUS IN CD4þCD25þ REGULATORY T CELLS FROM PATIENTS WITH RHEUMATOID ARTHRITIS BASIC SCIENCE Adam Cribbs1, Alan Kennedy2, Henry Penn3, Parisa Amjadi2, Patricia Green2, Fionula Brennan2, Bernard Gregory2 and Richard Williams2 1University of Oxford, Kennedy Institute of Rheumatology and Botnar O37. THE AUTOIMMUNE RISK GENE UBE2L3 IS HIGHLY Research Centre, 2University of Oxford, Kennedy Institute of EXPRESSED DURING B CELL PROLIFERATION AND IS Rheumatology, Oxford and 3Arthritis Centre, Northwick Park CORRELATED WITH PLASMABLAST AND PLASMA CELL Hospital, London, UK EXPANSION IN SLE

1 1 2 Background: RA is a chronic systemic inflammatory disease of Adrian M. Shields , Simon Vyse , Henning Walczak , Paul autoimmune origin, which arises from a breakdown in tolerance. H. Lehner3, Costantino Pitzalis4, Timothy D. Spector5, 1 4 Regulatory T cells (Tregs) play an indispensable role in maintaining Timothy J. Vyse and Myles J. Lewis tolerance by eliminating auto-reactive T cells from the periphery. We 1Department of , King’s College London, 2 have previously shown that methylation of the CTLA4 promoter at a University College London Cancer Institute, University College key NFAT-binding site could contribute to reduced CTLA-4 expression London, London, 3Cambridge Institute for Medical Research, 4 and impaired Treg function in a cohort of untreated RA patients. University of Cambridge, Cambridge, William Harvey Research However, others have shown that Treg function is normal when Institute, Barts and The London School of Medicine and Dentistry 5 isolated from patients with more established RA. In this study, we and Twin Research and Genetic Epidemiology, King’s College hypothesized that DMARD therapy can induce epigenetic London, London, UK changes that result in restoration of Treg function, and thus may explain why defective Treg function is not observed in established RA Background: Our previous work has shown that the rs140490 SNP patients. located at 270 bp of the UBE2L3 promoter region is strongly 14 Methods: Thymidine incorporation was used to measure suppression associated with SLE [P ¼ 8.6 10 , odds ratio 1.30 (95%CI 1.21, of T cell proliferation and ELISA was used to determine IFN-g 1.39], and the UBE2L3 risk haplotype drives increased UBE2L3 suppression. CTLA-4 and Foxp3 were measured by flow cytometry expression in B cells and monocytes. UBE2L3 is an E2 ubiquitin- and quantitative PCR (qPCR) in Tregs from healthy individuals and RA conjugating enzyme that critically regulates ubiquitination by the linear patients before and following 6 months of MTX treatment. To ubiquitin chain assembly complex (LUBAC). Linear ubiquitination characterize the in vitro effects of MTX, CD4þ T cells were isolated regulates NF-kB activation and TNF-a, IL-1 and CD40 inflammatory from healthy individuals and cultured in IL-2/IL-6/TNFa in the presence responses. Herein, we dissect in detail UBE2L3 expression in or absence of MTX, and Foxp3 expression was determined using lymphocyte subsets in SLE patients and healthy controls and correlate qPCR and flow-cytometry. Methylation of the foxp3 upstream the effects of the UBE2L3 genotype. enhancer was analysed by bisulphite-specific PCR, followed by Methods: Peripheral blood mononuclear cells from 36 patients with sequencing SLE and 27 healthy controls, stained with a 10-colour flow cytometric Results: We found that MTX treatment in RA patients resulted in antibody panel including intracellular staining for UBE2L3 expression demethylation of the FOXP3 upstream enhancer, leading to increased and analysed using an LSR Fortessa II cytometer. Clinical and Foxp3 protein expression. A consequence of higher levels of Foxp3 biochemical parameters of SLE disease activity were also collected. was a corresponding increase in the expression of CTLA-4, which in DNA was extracted from blood samples and UBE2L3 genotype was turn led to a reversal of defective Treg suppressive function. Therefore, determined using TaqMan PCR assays. we identify for the first time that MTX has epigenetic modifying effects, Results: Significantly higher levels of UBE2L3 expression were which may explain, in part, its ability to restore Treg suppression in RA identified in the plasmablast and plasma cell populations of both patients undergoing MTX therapy. SLE patients and control individuals relative to other B-lymphocyte Conclusion: Overall, our work suggests that identifying chemical subsets. SLE patients were found to have significantly greater UBE2L3 compounds that target the DNA methylation pathway in a manner that expression in their plasma cell population compared with controls leads to demethylation of the foxp3 locus may be a sensible strategy individuals (UBE2L3 MFI Control vs SLE: 1030 44 vs 1461 157, for uncovering new epigenetic therapies for RA. P ¼ 0.01). B-lymphocytes expressing high levels of the proliferation Disclosure statement: The authors have declared no conflicts of marker Ki-67, showed significantly greater expression of UBE2L3 than interest. non-proliferating B lymphocytes (UBE2L3 MFI Ki-67hi vs Ki-67lo: 837 86 vs 337 39, P < 0.0001). Activated B-lymphocytes expres- sing high levels of CD95 (Fas receptor) also expressed significantly O39. HYPOXIA INCREASES NEUTROPHIL EXTRACELLULAR greater levels of UBE2L3 in both control (UBE2L3 MFI CD95lo vs TRAP FORMATION AND ADHESION TO ENDOTHELIAL CELLS CD95hi: 362 25 vs 576 43, P < 0.0001) and SLE patients (UBE2L3 MFI CD95lo vs CD95hi: 386 35 vs 696 70, P < 0.0001), suggesting Akif A. Khawaja1,2, Charis Pericleous1, Luke W. Thomas3, that increased UBE2L3 expression is important for B cell activation. Margaret Ashcroft3, Joanna C. Porter2 and Ian Giles1 Flow cytometric data was stratified by genotype at rs140490. The T/T 1Centre for Rheumatology, 2Centre for Inflammation and genotype at rs140490 was associated with a significant expansion in Tissue Repair, University College London, London both plasmablast and plasma cell populations in SLE patients (both and 3Department of Medicine, University of Cambridge, P < 0.001), but not healthy controls. rs140490 genotype showed a Cambridge, UK trend to increased SLEDAI scores (P ¼ 0.06), but was not significantly correlated with ANA titre, anti-dsDNA antibody titre, C3/C4 hypocom- Background: RA is an autoimmune rheumatic disease characterized plementaemia or ESR level. by ACPA, endothelial dysfunction, platelet activation, synovial hyper- Conclusion: These data demonstrate that UBE2L3 plays an important plasia and hypoxia in affected joints. Circulating ACPA target role in plasmablast and plasma cell activation, proliferation and citrullinated proteins, which are generated by the activity of peptidyl differentiation in SLE. The T/T genotype at rs140490, was associated arginine deiminase (PAD)-2/4; however, the source of these autoanti- with a significant expansion of plasmablast and plasma cell popula- gens has yet to be clarified. Neutrophil extracellular traps (NETs) play a tions in SLE patients. This suggests that UBE2L3 genotype plays a critical role in the innate immune response and have been implicated in direct role in driving plasmablast and plasma cell differentiation, and several autoimmune pathologies. PAD-4 is required for the generation thus may promote increased disease activity in SLE. of NETs, which serve as a source of citrullinated proteins. Furthermore, Disclosure statement: The authors have declared no conflicts of NETs have been identified in serum and SF of patients with RA. NET interest. formation is enhanced by integrin engagement; however, the effects of i42 Thursday 30 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

hypoxia upon their generation are unknown. Therefore, we hypothe- five T cells to one monocyte for 7 days in the presence of anti-CD3 size that hypoxia modulates the cellular interactions leading to (OKT3), with or without etanercept, EPA or the control fatty acid, enhanced NETosis. linoleic acid. Expression of IL-17 and IFN-g was measured by Methods: Human umbilical cord endothelial cells (HUVECs) were intracellular staining and flow cytometry. grown in hypoxia (1% oxygen, 7.6 mmHg) to mimic conditions found in Results: Time-averaged EPA levels and the EPA/arachidonic acid (AA) the RA joint, or in normoxia (21% oxygen, 159.6 mmHg) in the ratio correlated with change in DAS for28 joints (DAS28) scores at 3 presence or absence of TNF-a or lipopolysaccharide (LPS). Levels of months (0.51, P ¼ 0.007 and 0.48, P ¼ 0.01, respectively), indicat- surface endothelial adhesion molecules, intercellular adhesion mole- ing that higher plasma EPA was associated with a greater reduction in cule (ICAM)-1, ICAM-2, vascular cell adhesion molecule (VCAM)-1 and DAS28. EPA was also associated with EULAR response (P ¼ 0.02), and E selectin, were measured by fluorescence-activated cell sorting. the DAS28 components, ESR (P ¼ 0.07) and tender joint count Neutrophils were isolated from whole blood donated by healthy (P ¼ 0.15) tended to be inversely associated with EPA tertile. An volunteers. Cell adhesion assays were performed in which binding increase in Th17 cells post-therapy has been associated with non- of 20,70-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxy- response to anti-TNF, and may be driven by increased production of methyl ester (BCECF-AM) labelled neutrophils to HUVEC monolayers IL-23. Prostaglandins produced from AA also promote Th17 cell or immobilized fibrinogen was measured using a fluorescent plate differentiation, and higher levels of EPA may impair AA-derived reader. A capture ELISA was established and tested to compare NET prostaglandin production. Thus, we examined the effect of etanercept release between experimental conditions. and EPA upon Th17 generation. Etanercept increased Th17 frequen- Results: Hypoxia modulated endothelial expression of ICAM-1, ICAM- cies in a dose-dependent manner (ANOVA P < 0.0001). Physiological 2, VCAM-1 and E selectin in response to TNF-a or LPS stimulation. doses of EPA, but not the control fatty acid, linoleic acid, prevented Hypoxia also enhanced neutrophil adhesion to HUVEC monolayers this etanercept-driven increase in Th17 frequency. from 3 3.1% to 47 12.0% of total cells added (P < 0.001). NET Conclusion: Dietary EPA supplementation might prove a simple release from phorbol 12-myristate 13-acetate (PMA)-stimulated method to improve anti-TNF outcomes in RA patients by suppressing neutrophils was elevated under hypoxia compared with unstimulated accumulation of Th17 cells. controls (49.6% vs 58.4%, P < 0.01). Cellular localization of key Disclosure statement: C.B. received a grant from Schering-Plough proteins involved in NET production in neutrophils was altered on (now Merck) that supported this work. I.M. received a grant from cultured under hypoxia. Endothelial-neutrophil co-culture experiments Schering-Plough (now Merck) that supported this work. P.T. received a demonstrated enhanced NETosis of PMA-stimulated neutrophils grant from Schering-Plough (now Merck) that supported this work. cultured under normoxia (P < 0.05). B.F. received a grant from Schering-Plough (now Merck) that Conclusion: We have shown that hypoxia modulates: adhesion supported this work. All other authors have declared no conflicts of molecule expression in HUVECs; neutrophil adherence to HUVEC interest. monolayers; and NET release. Furthermore, co-culture of neutrophils with HUVEC under normoxia elevates NET production on stimulation. O41. ANTIPHOSPHOLIPID ANTIBODIES ENHANCE Given that these processes are all relevant to the pathogenesis of CARDIOMYOCYTE APOPTOSIS IN A SIMULATED IN VITRO citrullinated antigens in RA, further experiments are currently under- CARDIAC ISCHAEMIA/REPERFUSION INJURY MODEL: A way to dissect the modulatory effects of hypoxia on NETosis and PROCESS DEPENDENT ON THE PRO-APOPTOTIC KINASE investigate the effects of ACPA-positive RA-IgG upon these cellular P38 MAPK conditions. Disclosure statement: The authors have declared no conflicts of Lauren Bourke1, James McCormick2, Vera M. Ripoll1, interest. Charis Pericleous1, Anastasis Stephanou2 and Yiannis Ioannou3 1Rheumatology, University College London, 2Molecular Medicine 3 O40. PLASMA LEVELS OF POLYUNSATURATED OMEGA 3 and Biological Unit, University College London and Arthritis EICOSAPENTAENOIC ACID ARE ASSOCIATED WITH ANTI- Research UK Centre for Adolescent Rheumatology, University TNF RESPONSE IN RHEUMATOID ARTHRITIS, AND INHIBIT College London, London, UK THE ETANERCEPT DRIVEN RISE IN TH17 CELL DIFFERENTIATION IN VITRO Background: A significant amount of myocardial damage during a myocardial infarction (MI) occurs during the reperfusion stage which is Louisa E. Jeffery1, Philip Calder2, Andrew Filer3, Karim Raza1, known as ischaemia/reperfusion (I/R) injury and can account for up to Christopher Buckley3, Iain McInnes4, Peter Taylor5 and 50% of total infarcted tissue post-MI. During the reperfusion phase a Benjamin Fisher3 complex interplay of multiple pathways and mechanisms are activated 1Immunity and Infection, University of Birmingham, Birmingham, which ultimately culminate in cell death primarily through apoptosis. 2Human Development & Health Academic Unit, Faculty of Medicine, There is some evidence from a lupus mouse model, within a University of Southampton, Southampton, 3Rheumatology Research mesenteric I/R injury model, that lupus IgG are pathogenic. Group, University of Birmingham, Birmingham, 4Glasgow Biomedical Additionally, anti-phospholipid (aPL) autoantibodies which are found Research Centre, University of Glasgow, Glasgow and 5Kennedy in 30–40% of lupus patients (termed secondary APS), as well as those Institute of Rheumatology, Oxford University, Oxford, UK with APS (primary APS) have been shown to specifically restore mesenteric I/R injury in a complement deficient mouse model. No Background: Anti-TNF agents have revolutionized the management of study has investigated the role of human lupus IgG in a heart model or RA, but a substantial proportion of patients fail to respond or do so the mechanism through which these aPL antibodies are potentially only partially. Understanding the reasons for inadequate response may pathogenic. guide choice of alternative biological agents, or permit optimization of Methods: Polyclonal IgG was purified by protein G from serum of anti-TNF therapy. Long-chain omega-3-polyunsaturated fatty acids patients with secondary APS (SLE/aPL positive (n ¼ 5), SLE/apL (PUFAs), including eicosapentaenoic acid (EPA), have immunomodu- negative (n ¼ 5), primary APS (n ¼ 6) and healthy controls (n ¼ 10), latory effects and supplementation is associated with modest efficacy which were age- and gender-matched. We utilized an established in RA. Omega-3-PUFAs cannot be synthesized de novo in humans, in vitro model of hypoxia/reoxygenation to simulate I/R injury. and conversion into long-chain omega-3-PUFAs is poor. Levels of Cardiomyocytes were isolated from 1–2-day-old rat pups and treated long-chain omega 3 PUFAs are therefore dependent upon dietary with 500 mg/ml polyclonal IgG from each group. The following day, intake from marine sources, which is highly variable. We sought to cells were exposed to simulated I/R injury for 4h in a hypoxic chamber determine whether plasma omega-3-PUFAs were associated with plus 4h of reoxygenation. Apoptosis was measured by assessment of response to anti-TNF agents in RA. caspase-3 cleavage using immunoblot and a terminal deoxynucleo- Methods: Twenty-two patents with established RA, who had failed at tidyl transferase dUTP nick end labeling (TUNEL) kit. least one DMARD and were on weekly MTX, were randomized to either Results: In the presence of IgG from patients with SLE, caspase-3 infliximab (3 mg/kg at weeks 0, 2, 6 and 10), or etanercept (25 mg cleavage was increased by 49.7% (S.D. 16.31) above untreated cells twice-weekly). Plasma was collected at baseline and at three months and in comparison with healthy controls (P < 0.0005). This finding was and its phosphatidylcholine fatty acid composition measured. The confirmed by TUNEL assay, which showed an increase of 54.2% in study was conducted in compliance with the Helsinki declaration and TUNEL positivity in cells treated with SLE IgG compared with ethical approval was obtained from the West Glasgow Ethics untreated. When SLE patients were divided into those that were aPL Committee. All subjects gave written informed consent. To assess positive (secondary APS) vs aPL negative, there was a greater increase the effect of etanercept and EPA upon T helper 17 (Th17) differentia- in cleaved caspase-3 in aPL positive patients (P ¼ 0.0051), with similar tion, CD4þCD25 T cells and monocytes were purified from the blood levels also observed in the presence of IgG from primary APS patients. of healthy donors by negative selection and co-cultured at a ratio of Phosphorylation of the pro-apoptotic kinase p38 MAPK was BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS Thursday 30 April 2015 i43

significantly increased in the presence of aPL positive IgG (primary and Based on recent research suggesting that skeletal muscle can act secondary) vs SLE/aPL negative (P ¼ 0.0010). Treatment of cells with as a source of diverse cytokines, we interrogated whether MHC-I the p38 MAPK inhibitor SB203580 significantly reduced levels of overexpression could cause microRNA dysregulation, ER stress cleaved caspase-3 in the presence of IgG from aPL positive patients pathway activation and release of myokines which could contribute (P ¼ 0.0256); however, there was no significant effect in the presence to the myositis phenotype. of healthy or aPL-negative IgG. Methods: C2C12 myotubes were transfected using Conclusion: In this in vitro simulated I/R injury model, IgG purified Lipofectamine2000M with a MHC I (H-2kb) overexpression vector in from patients with SLE and APS enhanced I/R injury, as assessed by the presence of salubrinal, an ER stress-blocking compound. caspase-3 cleavage and TUNEL. This in vitro data strongly implicates Successful transfection and upregulation of the H-2kb gene was aPL as being pathogenic in cardiac I/R injury and presents a potential confirmed by quantitative PCR (qPCR). Expression levels of miRNAs novel role of aPL via enhanced p38MAPK phosphorylation. and activation of the ER stress response was determined by qPCR Disclosure statement: The authors have declared no conflicts of and/or western blotting. Cytokine release from transfected C2C12 interest. myotubes was assessed by Luminex multiplex analysis. Results: Transfection of C2C12 myotubes with the H2-kb vector resulted in increased MHC I gene expression. H2-kb transfection also O42. IS MUSCLE A CHEMOTACTIC ORGAN IN THE resulted in activation of the ER stress pathway, evidenced by elevated IDIOPATHIC INFLAMMATORY MYOPATHIES (IIM)? Grp78, CHOP expression and X-box binding protein (XBP-1) splicing. OVEREXPRESSION OF MHC I (H-2KB) IN C2C12 MYOTUBES The expression levels of myomiRs (e.g. miR-133) and inflamma-miRs RESULTS IN RELEASE OF PRO-INFLAMMATORY CYTOKINES (e.g. miR-21) were affected by increased levels of MHC I in myotubes. Interestingly, inhibition of miR-133 expression in muscles of adult mice Adam P. Lightfoot1, Katarzyna Goljanek-Whysall1, Caroline led to increased expression of Grp78 and ATF4. Moreover, elevated V. Cotton1, Kate E. Earl1, Anne McArdle1 and Robert G. Cooper1 levels of IL-6, CCL2/MCP-1, CCL4/MIP1b and CCL5/RANTES were 1Musculoskeletal Biology, University of Liverpool, Liverpool, UK released from C2C12 myotubes following H2-kb transfection, which were ablated when myotubes were transfected in the presence of Background: The idiopathic inflammatory myopathies (IIM) are a salubrinal. heterogeneous group of rare autoimmune disorders which primarily Conclusion: MHC-I overexpression caused activation of ER-stress target skeletal muscle. IIM can be subclassified into PM, DM and responses, dysregulation of microRNA–target interactions associated inclusion-body myositis, with further clinical sub-types associated with with ER stress and pro-inflammatory cytokine release from C2C12 malignancy and interstitial lung disease. Patients present with myotubes, a process prevented by attenuation of the ER stress symmetrical proximal muscle weakness, elevated serum muscle response with salubrinal. These data suggest that MHC I over- enzymes and significant immune cell infiltrations into muscle expression induces muscle to act as a proinflammatory organ in the (CD8þCD4 T cells, B cells and macrophages). Upregulation of absence of immune cells. Furthermore, this MHC-1 myokine produc- MHC-I in vitro and in vivo is also a characteristic finding, and is tion in may play a chemotactic role, e.g to encourage immune cell associated with activation of the endoplasmic reticulum (ER) stress infiltrations into muscle. Attenuation of myokine release may represent response. MicroRNAs are emerging as novel regulators of gene a worthwhile therapeutic strategy to minimize inflammatory cell expression, and several microRNAs are predicted to regulate the infiltrations into IIM muscle. expression of ER stress-related genes. Moreover, pharmacological Disclosure statement: A.P.L. has received grants/research support activation of the ER stress response results in up-regulation in from Myositis UK. All other authors have declared no conflicts of proinflammatory muscle-derived cytokine (myokine) expression. interest. i44 Thursday 30 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

demonstrating subtle benefit from specific interventions without better tools for case definition and outcomes assessment. ADOLESCENT AND YOUNG ADULT Disclosure statement: The authors have declared no conflicts of RHEUMATOLOGY interest.

O44. AN INTEGRATIVE ANALYTICAL APPROACH TO SUBPHENOTYPING OF JUVENILE DERMATOMYOSITIS O43. THE EFFICACY OF A MULTIDISCIPLINARY Claire T. Deakin1, Shireena A. Yasin1, Katie A. Arnold1, INTERVENTION STRATEGY FOR THE TREATMENT OF 2 2 2 BENIGN JOINT HYPERMOBILITY SYNDROME IN Sarah L. Tansley , Zoe E. Betteridge , Neil J. McHugh , Janice L. Holton3, Tom S. Jacques4 and Lucy R. Wedderburn1 CHILDHOOD: A RANDOMIZED, SINGLE CENTRE PARALLEL 1 GROUP TRIAL Infection, Inflammation and Rheumatology Section, University College London Institute of Child Health, London, 2Rheumatology Peter J. Bale1, Vicky Easton2, Holly Bacon2, Emma Jerman3, Department, Royal National Hospital for Rheumatic Diseases, Bath, Kate Armon4 and Alex J. MacGregor1 3Division of Neuropathology, University College London Institute of 1Medical School, University of East Anglia, 2Paediatric and 4Developmental Biology and Cancer Programme, Physiotherapy, Norfolk and Norwich University Hospital, 3Paediatric University College London Institute of Child Health, London, UK Occupational therapy, Norfolk Community Health and Care NHS Trust and 4Jenny Lind Children’s Department, Norfolk and Norwich Background: JDM is a severe paediatric autoimmune condition University Hospital, Norwich, UK associated with muscle weakness and skin rashes, affecting approxi- mately 1 in 20 000 children. It encompasses a heterogeneous Background: Joint hypermobility is common in childhood and can be spectrum of symptoms, and can involve differing degrees of muscle associated with musculoskeletal pain and dysfunction. Current weakness, treatment-resistant rash, calcinosis, ulceration and involve- management is delivered by a multidisciplinary team but evidence of ment of the lung, gut or brain. Existing treatment consists of long-term efficacy is limited. This clinical trial aimed to determine whether a management involving steroids and immunosuppression; while some structured multidisciplinary intervention resulted in improved clinical patients are responsive and able to come off treatment by 2 years, outcomes compared with standard care. others fail to respond. In order to improve management of JDM, there Methods: A prospective randomized, single-centre parallel group trial is an imperative to define clinical subphenotypes that are identifiable comparing an 8-week individualized multidisciplinary intervention by unique biomarkers, and to investigate the biological mechanisms programme with current standard management. Standard manage- underpinning these subtypes. To that end, associations have been ment included an appointment with a paediatric rheumatologist who identified between certain clinical features and expression of the anti- provides diagnosis, advice and appointments with physiotherapy or MDA5, anti-NXP2 and anti-TIF1-g autoantibodies. occupational therapy if deemed clinically necessary. Children were Methods: Muscle biopsies (n ¼ 101) from the UK-wide JDM Cohort assessed for pain, function, coordination and strength at baseline and and Biomarker Study were scored using the validated score tool. at 3 and 12 months. Biopsy scores are being integrated with clinical features at the time of Results: 119 children, aged 5–16 years, with symptomatic hypermo- biopsy and at subsequent time-points. Principal component analysis bility were randomized to receive targeted multidisciplinary interven- (PCA) has been performed as a clustering technique in order to define tion (I) (n ¼ 59) or standard management (S) (n ¼ 60). Of these, 105 JDM sub-phenotypes. were followed to 12 months. There was a significant improvement in Results: Preliminary PCA has successfully identified two distinct child and parent reported pain, coordination and strength. However, clusters that correlate with the autoantibodies anti-MDA5 and anti- no added benefit could be shown from the intervention (Table 1). The Mi2, and reflect mild and severe histological changes, respectively. number of children showing significant pain reduction (40%) was 27 Separation between these clusters was predominantly on the basis of (50.0%) for I vs 21 (41.1%) for S. Those pain free at 12 months were 29 biopsy features in the Inflammatory and Muscle Fibre Domains in the (56.9%) for I vs 20 (45.5%) for S. The response was independent of the score tool. degree of hypermobility. Conclusion: These analyses represent the first step towards the Conclusion: This is the first RCT to compare a structured multi- identification of JDM sub-phenotypes that correlate with potential disciplinary intervention with standard care in symptomatic childhood biomarkers, and may enable definition of biological mechanisms hypermobility. The study demonstrates significant improvement behind such subtypes and a more targeted therapeutic approach for among subjects but no additional benefit from targeted intervention. JDM. The findings emphasize the benefit of informed diagnosis and Disclosure statement: The authors have declared no conflicts of management according to clinical need, but highlight the difficulty in interest.

O43 TABLE 1. Rate of change in primary and secondary outcomes over 12 months following each intervention Outcome variable Baseline Change in Change in standard score intervention group care group Child pain assessment (Wong–Baker Faces pain scale, 0–5, zero is the best; n ¼ 103), median (IQR) 2 (1–3) 1.42 (1.78 to 1.06) 1.31 (1.75 to 0.85) Parent observed pain assessment (0–100 VAS, with 0 as the best; n ¼ 105), mean (S.D.) 35.90 (26.46) 6.09 (12.90 to 0.73) 6.22 (13.62 to 1.18) Child health assessment questionnaire (0–3, with 0 as the best; n ¼ 104), mean (S.D.) 0.82 (0.63) 0.02 (0.12 to 0.16) 0.03 (0.13 to 0.64) Child health nine-dimensional utility (0–1, with 0 as the worst; n ¼ 104), mean (S.D.) 0.85 (0.11) 0.02 (0.01 to 0.04) 0.002 (0.02 to 0.03) Movement assessment battery for children (0–100, with 0 as the worst; n ¼ 104), mean (S.D.) 34.56 (28.61) 2.60 (2.92 to 8.11) 8.51 (3.17 to 13.86) Grip strength (dynamometer; n ¼ 104), mean (S.D.) 57.29 (28.30) 4.55 (0.16 to 8.94) 6.75 (2.85 to 10.66) IQR: interquartile range. BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS Thursday 30 April 2015 i45

O45. TUMOUR NECROSIS FACTOR INHIBITION IN 1Institute of Cellular Medicine, Newcastle University, 2Paediatric ENTHESITIS RELATED ARTHRITIS AND DISEASE MODIFYING Rheumatology, Great North Children’s Hospital, 3Department of EFFECTS IN AXIAL DISEASE Public Health and Wellbeing, Northumbria University and 4 1 1 1 Institute of Health and Society, Newcastle University, Newcastle Corinne Fisher , Ania Radziszewska , Linda Suffield , Margaret Hall- upon Tyne, UK Craggs2, Debajit Sen1 and Yiannis Ioannou1,3 1Arthritis Research UK Centre for Adolescent Rheumatology, Background: Recent advances in the management of paediatric and University College London, University College London Hospitals and adolescent rheumatology have developed the need for highly Great Ormond Street Hospital, 2Department of , University 3 specialist nurses within the multidisciplinary team. This has resulted College London Hospital NHS Trust and National Institute for Health in nurses working in shared care within other health care settings (e.g. Research Biomedical Research Centre, University College London community care, primary care, general paediatrics and adult rheuma- Hospitals, London, UK tology) demanding an enhanced knowledge base and new skill set. There is an important role for education and support for not only nurse Background: Patients with the enthesitis-related arthritis (ERA) specialists but also nursing colleagues. This study aims to establish subtype of JIA frequently require treatment with tumour factor the essential core learning needs of nurses delivering care to children inhibitors (TNFis). The efficacy and safety of TNFis have been clearly and young people with rheumatic disease within a variety of health demonstrated but the long-term efficacy is unknown and lower care settings. remission rates were attained in ERA compared with other subtypes Methods: Multi method research was conducted using online survey, of JIA in one recent study. We therefore undertook a review of TNFi focus groups and interviews with key nursing stakeholder groups use in our large cohort of adolescent and young adult patients with including clinical nurse specialists, nursing students and nurses from ERA. general paediatrics, community, research and adult rheumatology. An Methods: Patients with ERA (fulfilling ILAR criteria) who had been online survey of CNS within the British Society for Paediatric and treated with TNFi were identified from our cohort of 125 patients. A Adolescent Rheumatology (BSPAR; response rate 77%, with 27/35 review of demographics, disease phenotype, co-prescription of respondents) ascertained expert opinion about educational needs DMARDs and radiological assessment was undertaken. based on experience, knowledge and skills, and how these mapped to Results: 60% (75/125) of all patients with ERA were treated with TNFis the needs of different nursing groups. The survey results informed the at some point during their disease and 58.4% (73/125) remained on question frameworks for focus groups and one-to-one interviews to treatment. The median time to treatment with TNFi was 5 years after further explore educational needs of nurses working outside of the disease onset. DMARDs were coprescribed with TNFis in 97.3% (73/ specialism. All interviews and focus groups were recorded and 75) of patients but 24.0% (18/75) subsequently stopped taking these. transcribed; transcriptions along with free text comments from the Factors that made the prescription of TNFis more likely included axial survey were analysed qualitatively using thematic analysis. This study ERA (71% vs 37.8% of those with peripheral ERA only, P ¼ 0.00026), had ethical approval with informed consent from all participants. HLA B27 (71.8% vs 40% of those who were HLA B27 negative, Results: Four initial themes were extracted and described (Table 1): P ¼ 0.00438) and hip arthritis (76% vs 58% with no-hip arthritis, Need for increased awareness about rheumatic disease; impact of P ¼ 0.03318). Etanercept was the most frequent first-choice TNFi personal experience and nursing role; need for increased knowledge (65.8%), followed by adalimumab (19.2%) and infliximab (13.7%). about rheumatic disease and management; and design components 25.3% (19/75) had to switch biologic treatment mostly because of for a impactful learning and information resource. inefficacy (84.2%, 16/19). Two patients came off treatment perma- Conclusion: This study has identified core learning needs for all nently: both had no response to two TNFis and had little evidence of nursing groups. What is apparent from the results is that the level of acute inflammatory change on MRI prior to treatment. 10 patients tried need ranges from novice to expert. Future work will develop resources to stop TNFis having responded well to treatment (seven for possible to meet these individual educational requirements. remission, two with side effects and one for pregnancy). All relapsed Funding: This work was funded by an unrestricted educational bursary within 6 months and restarted treatment. 37/57(64.9%) patients with from Pfizer. axial ERA had SI joint (SIJ) MRI after starting TNFi (median time from Disclosure statement: H.E.F has received unrestricted educational starting biologic to scan, 14 months). Resolution of inflammatory bursaries from Pfizer, AbbVie, Roche, Genzyme, BioMarin and Sobi. change within the SIJs was seen in 29.7%, mild residual inflammatory All other authors have declared no conflicts of interest. change was seen in 51.4% and there was no improvement in 18.9%. Interestingly, 11 patients on TNFi (for >1 year) developed new bony ankylosis of their SIJs. O47. CLINICAL OUTCOMES OF YOUNG ADULTS WITH Conclusion: TNFi is an effective treatment for ERA and has an axial JUVENILE IDIOPATHIC ARTHRITIS FOLLOWING TRANSITION disease modifying effect with resolution of inflammatory change in TO ADULT CARE almost a third of patients with pre-biologic MRI evidence of sacroiliitis. Adam P. Croft1, Elizabeth Rankin2 and Alison Jordan1 However, some residual inflammation is seen on MRI in over half of all 1Rheumatology Research Group, Centre for Translational patients despite TNFis, perhaps explaining low remission rates in ERA. Inflammation Research, University of Birmingham and 2Department Factors that predict TNFi use include axial ERA, HLA B27 and hip of Rheumatology, Queen Elizabeth Hospital, University Hospitals arthritis. SIJ bony ankylosis may still occur despite TNFi and defining Birmingham NHS Trust, Birmingham, UK predictors of this warrants future study and analysis of larger cohorts of patients. Background: To describe the clinical outcomes of young adults with Disclosure statement: The authors have declared no conflicts of JIA following transition to adult care rheumatology services in a interest. prospective inception cohort of children managed with contemporary treatments. O46. WHAT ARE THE EDUCATIONAL NEEDS OF NURSES Methods: Adults diagnosed with JIA in childhood and transferred to INVOLVED IN THE CARE OF CHILDREN AND YOUNG PEOPLE adult care services between 2005 and 2010 were included. The WITH RHEUMATIC DISEASE? probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extra-articular manifestations), disease remission Nicola Smith1, Helen E. Foster1, Ruth Wyllie2, Christine English3, (inactive disease >12 months after discontinuing treatment) and of Barbara Davies3 and Tim Rapley4 receiving specific treatments were calculated.

O46 TABLE 1. Description of themes Theme Description 1. Need for increased Those without professional experience of paediatric rheumatology expressed need for increased awareness about the awareness presentation of rheumatic disease, in particular what’s normal, when to be concerned and what to do when concerned 2. Impact of personal experience The learning needs appeared dependent on past experience and what would be expected within their nursing role; those with and nursing role a professional experience and greater knowledge of children with rheumatic disease were more able to clearly define their learning needs 3. Need for increased knowledge This was highlighted across all nursing groups albeit the level of knowledge was stratified by what would be expected within their role; topics included understanding of conditions, treatment and medications, impact of disease and treatment on the child/young person and family, available support for themselves, patients and families and contemporary information and research to enable them to be well informed 4. Design components for an impactful All groups discussed design considerations in relation to format, structure and layout to create the ideal resource learning and information resource i46 Thursday 30 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

Results: 87 young adults were followed up for a minimum of 5 years musculoskeletal conditions such as JIA communicate with healthcare following the transition of clinical care to adult rheumatology services professionals about their pain experiences. Accurate pain commu- at a single centre. At the time of transition to adult services 21 (24%) nication facilitates effective pain and disease management. young adults with JIA (regardless of subtype) were on non-biological Standardized self-report measures including The Visual Analogue DMARD therapy, 9 (10%) young adults were treated with biological Scale (VAS) and the Faces Pain Scale, Revised (FPS-R) are considered DMARDs, 33 (38%) were in clinical remission and an additional 28 gold standard approaches commonly used in clinic; however, they do (32%) patients had inactive disease. Initial treatment included joint not reflect the multidimensional nature of pain in children with JIA. With injections and NSAIDs for oligoarthritis, DMARDs for polyarthritis and advances in technology, a new iPad application called This Feeling has systemic corticosteroids for systemic JIA. Following transition to adult been developed as an interactive tool to aid the communication of pain care 78(89%) of individuals achieved remission or inactive disease in children. This Feeling derives from the strong conceptual and within 2 years but only 52(60%) at 5 years. 58 (66%) individuals research base of an existing somatic assessment module of a experienced a relapse in disease or persistent disease activity computer assisted interview programme which uses images to requiring an escalation of treatment during the first 5 years following enable children to describe their pain. Our objectives were to explore the transfer of care. Overall, across all JIA subtypes within the first 5 whether This Feeling is an acceptable, usable and feasible system for years following transition, the probability of treatment with a biological communicating pain in children with JIA aged between 5 and 16; to therapy was 42%, experiencing a relapse of disease was 84%, ever compare children’s experiences of using this approach with traditional attaining inactive disease was 76% and discontinuing treatment at VAS and FPS-R; and to explore further development needs of This least once was 62%. Feeling. Conclusion: Whilst many young adults with JIA achieve either disease Methods: Children were recruited from the Childhood Arthritis remission or inactive disease prior to adulthood, persistent or relapsing Prospective Study, the largest prospective inception JIA cohort in disease in young adults is common within the first 5 years following the world, undertaken to study outcomes in children with JIA. A cross- transition to adult rheumatology care. Transitional care services must sectional, mixed-methods design utilized standardized measures (the develop to meet this clinical need through the delivery of multi- VAS and FPS-R) and This Feeling, which were administered to children disciplinary intensive treat-to-target clinical care aimed at optimizing attending outpatient appointments. Views on completing This Feeling disease control. were obtained from children and caregivers via a semistructured Disclosure statement: The authors have declared no conflicts of interview which was audio recorded and transcribed. interest. Results: 43 children (72% female; 31 girls and 12 boys) consented to the research. All children were able to use This Feeling. The majority of children (95%, 41/43) preferred using This Feeling to communicate O48. DEVELOPMENT AND FEASIBILITY TESTING OF their pain experiences compared with traditional pain reporting A NEW IPAD APPLICATION, THIS FEELING, TO AID measures. Most children particularly enjoyed the easy and fun nature COMMUNICATION OF PAIN IN CHILDREN WITH JUVENILE of the application, which took an average of 8 min to complete. IDIOPATHIC ARTHRITIS Children reported that This Feeling enabled them to accurately Pauline Tapping1, Amir Rashid2, Daniela Ghio2, Alice Chieng3, describe pain sites and types of pain as well as their emotional Phil Jimmieson4, Rachel Calam1, Lis Cordingley2 and responses. Children and caregivers identified points for development Wendy Thomson2 including the need for additional icons to describe pain; pain symbols 1School of Psychological Sciences, University of Manchester, to be labelled (particularly for younger children); and a zoom function 2National Institute for Health Research Manchester Musculoskeletal to enable children to select specific painful joints. Biomedical Research Unit, University of Manchester, 3Paediatric Conclusion: Preliminary findings indicate that This Feeling is an Rheumatology, Royal Manchester Children’s Hospital, Manchester acceptable and feasible aid for the communication of pain in children and 4Department of Computer Science, University of Liverpool, with JIA. Further adaptions are currently under development which will Liverpool, UK address the additional functions identified by this study. Disclosure statement: The authors have declared no conflicts of Background: Despite advances in pain assessment systems, ques- interest. tions remain over how best to help children with inflammatory i47 Thursday 30 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

damage and early death but who are more likely to respond to anti- TNF biologic therapy. GENETICS Disclosure statement: K.L.H. has received honoraria from Pfizer; and has received speakers fees from AbbVie. A.B. has received con- sultancy fees and/or grant support from Eli-Lilly, Pfizer and AbbVie but not in relation to the work presented. All other authors have declared O49. PERSONALIZED GENETIC MEDICINE: AMINO ACID no conflicts of interest. POSITIONS 11, 71 AND 74 IN HLA-DRB1 PREDICT DISEASE SEVERITY, MORTALITY AND TREATMENT RESPONSE IN O50. INTERNATIONAL IMMUNOCHIP STUDY IN THE RHEUMATOID ARTHRITIS—MULTI-CENTRE PROSPECTIVE IDIOPATHIC INFLAMMATORY MYOPATHIES IDENTIFIES COHORT STUDIES GENETIC DIFFERENCES BETWEEN CLINICAL SUBGROUPS, Sebastien Viatte1, Darren Plant1, Buhm Han2,BoFu1, AND CONFIRMS HLA ALLELES AS STRONGEST GENETIC Annie Yarwood1, Wendy Thomson1, Deborah P. M. Symmons3, RISK FACTOR 1 4 3 Jane Worthington , Adam Young , Kimme L. Hyrich , Ann 1 2 3 5 6 7 Simon Rothwell , Robert G. Cooper , Ingrid Lundberg , Frederick W. Morgan , Anthony G. Wilson , John D. Isaacs , 4 5 6 7 2 1 W. Miller , Peter K. Gregersen , Jiri Vencovsky , Katalin Danko , Soumya Raychaudhuri and Anne Barton 8 9 10 1 Lucy R. Wedderburn , Vidya Limaye , Albert Selva-O’Callaghan , Arthritis Research UK Centre for Genetics and Genomics, University 11 12 13 2 Michael G. Hanna , Lauren M. Pachman , Ann M. Reed , of Manchester, Manchester, UK, Program in Medical and Population Øyvind Molberg14, Olivier Benveniste15, Pernille Mathiesen16, Genetics, Broad Institute of MIT and Harvard, Boston, MA, USA, Timothy Radstake17, Andrea Doria18, Jan De Bleecker19, William 3 Arthritis Research UK Centre for Epidemiology, University of E. Ollier20, Terrance P. O’Hanlon4, Annette T. Lee5, Hector Chinoy1 4 Manchester, Manchester, UK, St Albans City Hospital, Health and and Janine Lamb20 Human Sciences Research Institute, University of Hertfordshire, St 1Centre for Musculoskeletal Research, University of Manchester, Albans, UK, 5NIHR Leeds Musculoskeletal Biomedical Research Manchester, 2Department of Musculoskeletal Biology, University of Unit, Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Trust, Liverpool, Liverpool, UK, 3Department of Medicine, Karolinska Chapeltown Road, Leeds, UK, 6Conway Institute of Biomolecular & Institutet, Stockholm, Sweden, 4Environmental Autoimmunity Group, Biomedical Research, University College Dublin, Dublin, Ireland and NIH, Bethesda, MD, 5Center for Genomics & Human Genetics, The 7Musculoskeletal Research Group, Institute of Cellular Medicine, Feinstein Institute, Manhasset, NY, USA, 6Institute of Rheumatology, Newcastle University and Newcastle upon Tyne NHS Foundation Charles University, Prague, Czech Republic, 7Third Department of Trust, Framlington Place, Newcastle upon Tyne, UK. Internal Medicine, University of Debrecen, Debrecen, Hungary, 8Arthritis Research UK Centre for Adolescent Rheumatology, Background: The shared epitope (SE) is a group of alleles of the HLA- University College London, London, UK, 9Rheumatology Unit, Royal DRB1 gene and was thought to have the strongest effect on RA Adelaide Hospital, Adelaide, Australia, 10Internal Medicine Department, susceptibility. However, recently, HLA-DRB1 position 11, outside of the Vall d’Hebron General Hospital, Barcelona, Spain, 11National Hospital classical SE, has been shown to be a stronger predictor of RA for Neurology & , UCL, London, UK, 12Ann & Robert H. susceptibility. Positions 11, 71 and 74 define 16 haplotypes, the effect Lurie Children’s Hospital of Chicago, Northwestern University Feinberg of which ranges from risk to protective on RA susceptibility. Their effect School of Medicine, Chicago, IL, 13Division of Rheumatology, Mayo on RA severity, treatment response or mortality in patients has not Clinic, Rochester, MN, USA, 14Department of Rheumatology, Oslo previously been studied. Our objectives were to assess whether HLA- University Hospital, Oslo, Norway, 15Pitie´ -Salpeˆ trie` re Hospital, AP-HP, DRB1 positions 11, 71 and 74 can also be used to predict radiological Paris, France, 16Paediatric Clinic, Copenhagen University Hospital, outcome, anti-TNF response and mortality in patients with RA. Copenhagen, Denmark, 17Department of Rheumatology & Clinical Methods: We used 3 independent prospective cohort studies: the Immunology, University Medical Center Utrecht, Utrecht, The Norfolk Arthritis Register (1691 patients with 2811 X-rays); the Early Netherlands, 18Division of Rheumatology, University of Padova, Rheumatoid Arthritis Study (421 patients with 3758 X-rays); and a Padova, Italy, 19Department of Neurology, Ghent University, Ghent, cohort from 57 UK centres (BRAGGSS; 1846 patients with Belgium and 20Centre for Integrated Genomic Medical Research, treatment response). HLA typing was determined using a reverse University of Manchester, Manchester, UK dot-blot method or dense genotyping of the HLA region by the ImmunoChip array, followed by imputation. Longitudinal modeling of Background: The idiopathic inflammatory myopathies (IIM) are a the presence of erosions was performed with generalized estimating heterogeneous group of rare autoimmune diseases characterized by equation (GEE) models, whilst the Larsen score was modeled by muscle weakness and extramuscular manifestations such as skin Generalized Linear Latent and Mixed Modeling (GLLAMM). Change rashes, interstitial lung disease and an increased association with in the DAS for 28 joints was modeled with linear regression and malignancy. Recent candidate gene studies in IIM and a genome-wide EULAR response with ordinal logistic regression. Cox proportional association study in DM suggest a shared genetic architecture with hazard models were used for all cause and cardiovascular mortality other autoimmune diseases. We therefore conducted a genetic studies. association study using the Immunochip; a custom Illumina array Results: Valine at position 11 of HLA-DRB1 (Val11) is a new and the containing coverage of 186 established pan-autoimmune susceptibility strongest independent genetic determinant of radiological damage in loci identified from other autoimmune diseases. RA, and this finding has been replicated in separate cohorts [odds ratio Methods: We genotyped 2566 IIM cases of Caucasian descent (OR) in NOAR 1.75 (95%CI 1.52, 2.01), P ¼ 8.7 1015]. Positions 71 comprising DM, JDM and PM fulfilling Bohan and Peter classification and 74 represent independent predictors and the three positions criteria, and inclusion body myositis fulfilling Griggs, European define 16 haplotypes strongly associated with disease outcome Neuromuscular Centre and Hilton-Jones criteria. Samples have been (multivariate P ¼ 2.83 1012), superseding the SE. The hierarchy, collected from 14 countries through the Myositis Genetics Consortium. ranging from risk to protective effects, is perfectly correlated with that Data from all cases and 15 651 matched Caucasian control samples observed for disease susceptibility. HLA-DRB1 haplotypes associated were combined for clustering, and SNPs were called using GenCall. with RA susceptibility and severe outcome are also predictors of good SNP quality control (QC) was based on a call rate of >98% and/or treatment response with anti-TNF therapy. For example, the cluster separation score >0.4. Sample QC was based on a call rate Val11Lys71Ala74 haplotype, carried by 52% of patients, is associated >98%. Samples with extreme heterozygosity, related individuals and with good EULAR response [OR 1.24 (95%CI 1.07, 1.44) ancestral outliers were also removed. Analysis was performed in P ¼ 5.31 103). On average, 17 patients need to be treated with PLINK version 1.07 using logistic regression adjusting for the top 10 anti-TNF to see one more patient responding better, based solely on principal components. the carriage of this haplotype. Both all-cause and cardiovascular Results: Initial analysis of 114 422 SNPs confirmed the MHC as the most mortality are also predicted by the 16 haplotypes. strongly associated region. PTPN22 was the only non-HLA locus to reach Conclusion: Combinations of amino-acids at positions 11, 71 and 74 genome-wide significance of P < 5 108, previously associated in a of the HLA-DRB1 gene predict severe disease, treatment response candidate gene study. Using a second suggestive tier of significance of and mortality in RA, superseding the classical SE. At disease onset, P < 2.25 105, there was evidence for association at additional loci, this allows stratification of patients to identify those at risk of joint including STAT4, UBE2L3-YDJC and DGKQ-GAK. A subanalysis of PM i48 Thursday 30 April 2015 BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS

(n ¼ 931) strengthened the association with PTPN22 and suggested PM- successfully identified over 100 loci associated with disease onset. specific loci including UBE3B/MMAB, NAB1 and IL18R1. In a combined After the HLA region and PTPN22, the strongest association to both DM and JDM analysis (n ¼ 1360), there is no evidence of association with seropositive and seronegative RA is seen within the ANKRD55 gene, on PTPN22, suggesting the association with total IIM is driven by the chromosome 5q11. ANKRD55 is an unexplored gene that could provide stronger association with the PM subgroup. There were fewer associa- novel insights into the biological pathways that underpin RA and also be tions of suggestive significance in DM and JDM; however, the GSDMB a putative novel therapeutic target. The objective was to utilize well- locus is of particular interest. powered genetic data in order to fine-map the region, and through Conclusion: This is the largest genetic association study to date in bioinformatic data and functional experiments, to generate robust IIM. The data confirm that HLA is the most associated locus in IIM and evidence for the causal variant and causal gene at the 5q11 locus. its clinical subgroups, and that the association of PTPN22 in IIM may Methods: As part of the ImmunoChip project, 60 single nucleotide be driven by its preferential association with PM. Identification of polymorphisms (SNPs) in a 0.1 cM recombination block around the further novel loci at a suggestive level of significance may differ previous lead genome-wide association study marker at the 5q11 between clinical subgroups of myositis. The IIMs are a heterogeneous locus, rs6859219, were analysed for their association in 11 475 cases set of diseases; additional clinical subgroup specific analyses as well and 15 870 controls. Conditional logistic regression and haplotype as antibody specific analyses are thus planned. analysis were conducted in order to fully characterize the genetic Disclosure statement: The authors have declared no conflicts of interest. architecture of the region. Bioinformatic tools were subsequently used in order to examine and prioritize SNPs based on their regulatory potential. Correlation of the putative variants with expression of nearby O51. DNA METHYLATION PROFILING OF SYNOVIAL FLUID- genes (eQTL) was carried out in whole blood, CD4þ and CD8þ T cell DERIVED FIBROBLAST-LIKE SYNOVIOCYTES FROM subsets, and chromatin immunoprecipitation (ChIP) experiments for PATIENTS WITH RHEUMATOID ARTHRITIS REVEALS the histone modification H3K4me1, a marker of enhancers was carried COMMON AND DISTINCT CHANGES RELATIVE TO THEIR out in lymphoblastoid B cell lines. TISSUE-DERIVED COUNTERPARTS Results: Genetic fine-mapping using ImmunoChip data refined the John R. Glossop1,2, Kim E. Haworth1, Richard D. Emes3,4, association at the 5q11 locus to a single signal, rs71624119 Nicola B. Nixon2, Jon C. Packham2, Peter T. Dawes2, (P ¼ 5.59 1020), highly correlated with 4 other SNPs (LD R2 0.8). Anthony A. Fryer1, Derek L. Mattey1,2 and William E. Farrell1 Bioinformatic prioritization implicated two of these SNPs, rs10065637 1Institute for Science and Technology in Medicine, Keele University, and rs6859219, with evidence of regulatory activity, potentially located Keele, 2Rheumatology, Haywood Rheumatology Centre, Stoke-on- within an intronic enhancer element. Evidence was obtained for Trent, 3School of and Science, University of correlation of these SNPs with expression of ANKRD55 (eQTL) in both 5 þ 3 Nottingham, Sutton Bonington and 4Advanced Data Analysis Centre, whole blood (P ¼ 3.85 10 ) and CD4 (P ¼ 3 10 ), but not þ University of Nottingham, Sutton Bonington, UK significant in CD8 T cells. Bioinformatic analysis also indicates that ANKRD55 is coregulated with other immune molecules associated Background: Fibroblast-like synoviocytes (FLS) from patients with RA with RA, including CD28, part of the T cell receptor signalling pathway. display an aggressive, invasive phenotype and play a key role in joint Preliminary ChIP data was suggestive of a greater enrichment for the destruction. Increasing evidence indicates that alterations to the histone mark of enhancer activity, H3K4me1, with carriage of the risk epigenome, including DNA methylation, contribute to the FLS allele at both rs10065637 and rs6859219. phenotype in RA. Herein, we performed the first genome-wide profiling Conclusion: Although the RA associated loci at 5q11 contains strong of DNA methylation in FLS derived from SF, as a more readily immunological candidates for causality, including IL6ST and IL31RA, accessible source of disease-associated cells, in patients with RA. our preliminary findings implicate ANKRD55, a gene of unknown Methods: Synovial fluid samples were collected during routine function. Determining the causal SNP, gene and disease mechanism in arthrocentesis from 12 Caucasian patients with RA and OA. FLS were this, the third most associated RA region, uniquely conferring similar isolated and expanded in vitro using standard adherent cell culture risk to both seropositive and seronegative disease, has the potential to methods. Genomic DNA was extracted, bisulfite-converted and subse- illuminate novel pathways and therapeutic targets in disease. quently hybridized to HumanMethylation450 BeadChips for quantitative Disclosure statement: The authors have declared no conflicts of assessment of genome-wide DNA methylation at over 480 000 CpG interest. dinucleotides. Data were analyzed using NIMBL software. A CpG was considered to be differentially methylated in RA FLS relative to OA FLS if O53. PTPN22 IS ASSOCIATED WITH SUSCEPTIBILITY TO the mean difference in methylation b-value was at least 0.1 and was PSORIATIC ARTHRITIS BUT NOT PSORIASIS: EVIDENCE FOR statistically significant following adjustment for multiple testing. A FURTHER PSA-SPECIFIC RISK LOCUS Candidate genes were validated by bisulfite pyrosequencing. 1 2 1 2 Results: Genome-wide profiling identified 328 CpGs (representing 195 John Bowes , Sabine Lohr , Ashley Budu-Aggrey , Steffen Uebe , 1,3 4 5 genes) that were differentially methylated between RA and OA fluid- Ian N. Bruce , Marie Feletar , Helena Marzo-Ortega , 5 6 7 derived FLS. The majority (80%) of these sites/genes were hypo- Philip Helliwell , Anthony W. Ryan , David Kane , methylated in RA FLS. Comparison of these 195 genes with those Eleanor Korendowych8, Gerd-Marie Alenius9, Emiliano Giardina10, 11 6 12 identified in two studies of tissue-derived FLS revealed 73 genes (40%) Jonathan Packham , Ross McManus , Oliver Fitzgerald , 8 4 13 that were common with at least one of these studies, and where 22 Neil McHugh , Matthew A. Brown , Frank Behrens , 13 2 1,3 2 genes shared identity with both studies. Pyrosequencing analysis Harald Burkhardt , Ulrike Huffmeier , Pauline Ho , Andre Reis 1,3 confirmed altered methylation of these genes and identified additional and Anne Barton 1 sites in some of the genes which also showed methylation changes Arthritis Research UK Centre for Genetics and Genomics, University of similar to those determined at the array-identified site. We also identified Manchester, Manchester, UK, 2Institute of Human Genetics, University 122 differentially methylated genes that were unique to fluid-derived of Erlangen-Nuremberg, Erlangen, Germany, 3The Kellgren Centre for FLS, and which perfectly segregated RA from OA-derived FLS. Rheumatology, Central Manchester Foundation Trust, NIHR Conclusion: SF-derived RA FLS show altered DNA methylation across Manchester Biomedical Research Centre, Manchester, UK, 4The multiple genes and a significant proportion of these are common with Diamantina Institute, University of Queensland, Queensland, Australia, those identified in tissue-derived FLS. These data identify a number of 5NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds potential candidate genes and support the use of fluid-derived FLS for Institute of Molecular Medicine, University of Leeds, Leeds, UK, future investigations of epigenetic dysregulation in RA synovial fibroblasts. 6Department of Clinical Medicine, Institute of Molecular Medicine, Disclosure statement: The authors have declared no conflicts of interest. Trinity College Dublin, Dublin, 7Adelaide and Meath Hospital, Trinity College Dublin, Dublin, Ireland, 8Royal National Hospital for Rheumatic Diseases and Department of Pharmacy and Pharmacology, University O52. CHARACTERIZATION OF RHEUMATOID ARTHRITIS 9 SUSCEPTIBILITY LOCUS, 5Q11 (ANKRD55) of Bath, Bath, UK, Department of Public Health and Clinical Medicine, University Hospital, Umea, Sweden, 10Centre of Excellence for Kate McAllister1, Gisela Orozco1, Jane Worthington1 and Genomic Risk Assessment in Multifactorial and Complex Diseases, Stephen Eyre1 University of Rome, Rome, Italy, 11Health Services Research Unit, 1Arthritis Research UK Centre for Genetics and Genomics, Centre for Institute of Science and Technology in Medicine, Keele University, Musculoskeletal Research, Institute of Inflammation and Repair, Keele, UK, 12Department of Rheumatology, St Vincent’s University Faculty of Medical and Human Sciences, Manchester Academic Hospital, University College Dublin, Dublin, Ireland, 13Division of Health Science Centre, Stopford Building, University of Manchester, Rheumatology and Fraunhofer IME-Project-Group Translational Manchester, UK Medicine and Pharmacology, Goethe University, Frankfurt, Germany

Background: RA is a chronic and disabling disease with no known Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis cure. RA has a strong genetic component and genetic studies have associated with psoriasis with the prevalence rate of PsA in psoriasis BSR AND BHPR ORAL PRESENTATION OF ABSTRACTS Thursday 30 April 2015 i49

patients estimated to be 14% in UK populations. PsA is a complex health in early RA has received less attention. We evaluated potential disease where disease liability is comprised of environmental risk causes of low mental health – assessed using the SF-36 mental factors and a polygenic susceptibility background. The genetics of component summary score (MCS) – in 424 early, active RA patients PsA susceptibility is not fully understood; PsA is estimated to have a enrolled to a clinical trial. We tested the hypothesis that reduced larger genetic component than psoriasis alone and recent studies have mental health in early RA is driven by genetic risk of depression; RA identified PsA-specific loci that begin to explain this increased burden, severity [DAS for28 joints (DAS28) and HAQ]; and pain levels. for example, amino acids in HLA-B and our own Immunochip study Methods: We studied 424 European patients previously recruited to reported evidence for PsA-specific risk at chromosome 5q31 and the Combination Anti-Rheumatic Drugs in Early RA trial. Patients were IL23R. randomized to DMARD monotherapy or combination therapy and Methods: In this study we attempt to validate 14 single nucleotide assessed 6 monthly for 2 years. DNA was genotyped (ImmunoChip polymorphisms (SNPs) selected from our recent Immunochip study platform). A polygenic risk score (PRS) for depression was constructed (P < 1 104) in a combined collection of 3139 PsA cases and 11 078 using 1908 susceptibility variants of nominal association from the controls from UK, Republic of Ireland, Germany, Australia, Sweden recent major depressive disorder genome-wide association study and Italy. Genotyping was performed using the Life Technologies mega-analysis. MCS measures mental health on a scale of 0–100: QuantStudio genotyping platform and association testing was per- higher scores indicate better health. As MCS scores increased linearly formed using PLINK. For loci not previously reported for psoriasis we over 2-years, their associations were tested using a repeated- compare effect sizes using multinomial logistic regression, performed measures linear mixed-effects model. Correlated random-effects in Stata, and directly compare PsA genotypes from Immuochip accounted for within-individual correlations in MCS over time. MCS (n ¼ 1936) to the psoriasis WTCCC2 study (excluding known PsA, was included as the response variable. Time, treatment and each of n ¼ 1784). To control for phenotype misclassification with RA, we the variables of interest [genetic PRS, DAS28 and its components, include a genetic risk sore comprised of the 41 RA susceptibility HAQ, pain visual analogue scale (VAS)] were included as fixed-effects reported in the RA Immunochip study as a covariate and re-analysed predictor variables. Age, gender, disease duration and RF status were the PsA Immunochip. not included as modelling covariates, as they did not associate with Results: We find genome-wide significant association to rs2476601, MCS (at the 10% significance level). Ethical approval was obtained; all mapping to the gene PTPN22 [P ¼ 1.490 10–9, odds ratio (OR) 1.32]. patients provided consent. There was no evidence for association to rs2476601 in the psoriasis Results: Increased genetic risk for depression associated with worse WTCCC2 cohort (P ¼ 0.34) and the effect estimates were found to be mental health (Table 1). In a univariate analysis the depression PRS significantly different between PsA and psoriasis (P ¼ 3.2 10–4). had a significant inverse association with MCS (P ¼ 0.007). Lower Direct comparison of genotypes for PsA and psoriasis found mental health scores were also seen with more severe RA; in univariate significant association to an increased risk of PsA (P ¼ 4.4 10–4, analyses, DAS28 (P < 0.001) and HAQ (P < 0.001) inversely associated OR 1.3). The association to PTPN22 in the PsA Immunochip data was with MCS. Additionally, high pain levels associated with poorer mental not affected by the inclusion of the RA-GRS as a covariate. In addition, health (pain VAS P < 0.001). All these variables remained significant in we find genome-wide significant association to the previously reported a multivariate model, indicating their effects were independent of one psoriasis risk loci; NOS2 (rs4795067, P ¼ 5.27 10–9). No other SNPs another. Evaluating individual DAS28 components suggested inflam- reached genome-wide significance in the combined dataset. matory measures were more important than non-inflammatory ones. In Conclusion: For the first time, we report genome-wide significant univariate analyses the swollen joint count, tender joint count (TJC), association of PTPN22 (rs2476601) to PsA susceptibility, a locus ESR and patient global all associated with MCS; in a multivariate associated with many autoimmune diseases. The risk allele (A) and analysis, the TJC was no longer significant (P ¼ 0.163). direction of effect are consistent with previous reports for RA and type Conclusion: The aetiology of reduced mental health in early RA is I diabetes, but opposite of that reported for Crohn’s disease. We multifactorial. Our study suggests it is driven by genetic risk for provide evidence that this is a PsA-specific risk locus as no depression, disease severity and pain levels. Inflammation is an association to psoriasis was observed in the WTCCC2 cohort and important driver, with inflammatory DAS28 components appearing the effect estimates are significantly different between PsA psoriasis more important than non-inflammatory aspects. when compared in multinomial logistic regression. Disclosure statement: J.E. has received a Medical Research Council Disclosure statement: The authors have declared no conflicts of Studentship. F.M. has received salary support from the National interest. Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King’s College London. I.C.S. has received an O54. REDUCED MENTAL HEALTH IN EARLY RHEUMATOID Arthritis Research UK Clinical Research Fellowship and an NIHR ARTHRITIS IS ASSOCIATED WITH GENETIC SUSCEPTIBILITY Clinical Lectureship. All other authors have declared no conflicts of FOR DEPRESSION, DISEASE SEVERITY AND PAIN LEVELS interest. Jack Eusden1, Faith Matcham2, Sophia Steer3, Andrew P. Cope4, Cathryn M. Lewis5 and Ian C. Scott4 1Social, Genetic and Developmental Psychiatry, 2Psychological O54 TABLE 1. Associations with mental component summary scores in CARDERA 3 Medicine, King’s College London, Rheumatology, King’s College Variable Univariate analysis Multivariate analysis Hospital, London, 4Academic Rheumatology and 5Medical and Molecular Genetics, King’s College London, London, UK b P-value b P-value Depression PRS 1.50 0.007 1.16 0.016 Background: Depression and reduced mental health are prevalent in DAS28 2.56 <0.001 0.93 <0.001 RA. They associate with an impaired quality of life and increased HAQ 6.53 <0.001 4.03 <0.001 healthcare utilization. Several studies have assessed causes of Pain VAS 0.16 <0.001 0.07 <0.001 depression in established RA, reporting associations with pain, CARDERA: Combination Anti-Rheumatic Drugs in Early RA; DAS28: DAS for28 disability and tender joint counts. The cause of reduced mental joints; PRS: polygenic risk score; VAS: visual analogue scale. i50 Tuesday 28 April 2015 POSTER VIEWING I

condition that has been associated with a novel antibody to hydroxy- methyl-glucuronyl Co-enzyme A reductase (HMGCR). The HMGCR CASE REPORTS antibody is a very specific finding to the autoimmune variety of statin myopathy, as studies have shown it to be absent in traditional statin- related myopathy. The biopsy findings with statin-related autoimmune necrotizing myopathy tend to show significant necrosis, with the 001. FALSE-POSITIVE HEPATITIS B SEROLOGY DUE TO absence of lymphocytic infiltrations, signifying a lack of inflammatory SUSPECTED CROSS-REACTIVITY IN A PATIENT WITH changes which would be seen with PM or DM. It is very interesting that RHEUMATOID ARTHRITIS there is a substantial group of patients who develop an autoimmune necrotizing myopathy with antibodies to HMGCR whom have not been Rebecca L. Batten1, Brendan Payne2, Stuart McPherson3 and 1 exposed to a statin at all. This indicates there are other pathogenic Ben Thompson mechanisms at play, which at the time of writing, are unknown. This is 1Musculoskeletal Department, Freeman Hospital, 2Infectious 3 a case describing a patient who was diagnosed with statin-induced Diseases and Virology, and Liver Unit, Freeman Hospital, autoimmune necrotizing myopathy. Newcastle Hospitals NHS Trust, Newcastle upon Tyne, UK Methods: A 58 year old man presented to the Rheumatology Outpatient Department with a 3 month history of upper arm pain and Background: Consensus statements and manufacturer data sheets lower leg fatigability. Climbing the flight of stairs to his 2nd floor flat suggest patients with RA considered for rituximab therapy should be was proving more difficult. He felt systemically unwell. He was screened for HBV. Patients with positive screening tests are diagnosed with hypertension and hypercholesterolaemia by his considered for other therapies or anti-viral treatment. We report a general practitioner 6 months ago, and was taking simvastatin for 3 case of suspected HBV serology cross-reactivity in a patient months, but had to stop this because he developed generalized with seropositive RA, and consider the potential mechanisms and muscle pain. He was noted to have mild proximal muscle weakness in clinical implications of false-positive screening results in this patient his legs. His upper limbs were more difficult to assess due to bilateral group. impingement. Creatine kinase (CK) was raised at 4800 IU/l. A muscle Methods: A 59 year old male with an established diagnosis of biopsy was arranged which showed a necrotizing myopathy with a seropositive erosive RA exhibited florid synovitis on musculoskeletal paucity of inflammatory change. ultrasound, despite treatment with MTX and etanercept. His serology Results: He was initially managed with high-dose prednisolone 60 mg was strongly positive for both anti-CCP antibodies (>340 U/ml]) and daily. Blood tests were sent to Oxford for analysis and his serum was RF (>640). He was considered for rituximab and screening investiga- HMGCR antibody positive. Importantly, he was negative for all other tions were performed. tested antibodies, including those against signal recognition particle Results: At initial screening, HBeAb and HBcAb were detected; (SRP) and Jo-1. CT of the thorax, abdomen and pelvis showed no HBsAb and HBsAg were negative; and HBV (core) DNA was not evidence of malignancy. The diagnosis of statin-induced necrotizing detected. Liver function tests were normal. Results were consistent autoimmune myopathy was made and AZA was added as the patient’s with past HBV infection, and he was referred to . No alcohol consumption was deemed too high for MTX. He responded specific risk factors for exposure were identified, although his work as well to the combination of prednisolone and AZA, with muscle power a health professional had exposed him to potential infection. He was improving and CK normalizing. offered prophylactic anti-viral therapy but chose to avoid rituximab, Conclusion: This case is a rare example of statin-associated and alternative treatments were considered. Six months later, on autoimmune necrotizing myopathy with antibodies to HMGCR. This repeat testing HBeAb was now negative, and very low-level reactivity diagnosis should be considered where symptoms and CK fail to was detected in one of two assays for HBcAb. Previous assays were resolve despite the withdrawal of statin, as traditional statin myopathy reviewed in the light of these results, and the likelihood of false- is a self-limiting condition. Where this diagnosis is suspected, serum positive results was considered. Roche Elecsys and Biomerieux VIDAS should be tested for the HMGCR antibody and treatment should be assays both used mouse mAbs as reagents. None of the assays initiated with high-dose steroids and steroid sparing medication. IVIG reported testing for cross-reactivity with Rhesus factor (RhF). Quoted was not required in this case. specificity ranged from 99.7% to 99.9%. Disclosure statement: The author has declared no conflicts of Conclusion: There are a number of possible explanations for false- interest. positive HBV serology in a patient with seropositive RA: RhF may non- specifically bind the test antigen reagent used in the assay; RhF (an IgM class anti-human IgG antibody) could bind the mouse mAb IgG 003. A CASE OF DISSEMINATED VARICELLA IN A PATIENT used in the assay; and the patient’s serum may contain anti-drug ON BIOLOGIC THERAPY BUT WITH PRIOR IMMUNITY: antibodies due to previous biologic exposure, which may bind the mAb IMPLICATIONS FOR ADVICE AND MANAGEMENT used in the assay. We plan to carry out further tests on stored serum to FOLLOWING CONTACT WITH CHICKENPOX investigate these hypotheses. Rheumatologists should be aware of the Matthew J. Cates1 possibility of false-positive screening tests for HBV. Such results can 1Department of Rheumatology, Royal Cornwall Healthcare Trust, have a significant impact on the care of people with RA, either causing Truro, UK potentially effective treatment strategies to be avoided, or exposing them to the risks of anti-viral therapy unnecessarily. Patients with Background: Primary varicella zoster virus (VZV) infection causes seropositive disease, who are sometimes offered rituximab preferen- varicella (chickenpox) with reactivation later in life causing herpes tially, may be more susceptible to false-positive results because of the zoster (shingles). Varicella following a contact with the virus in patients presence of antibodies that cross-react with the assays used. We with previous immunity is rare. recommend a high index of suspicion in these cases, and early Methods: A case of varicella in an immunosuppressed patient with discussion with a virologist and a hepatologist. previous immunity is reported and treatment options discussed. Disclosure statement: The authors have declared no conflicts of Results: A 33 year old woman presented to the Accident and interest. Emergency Department with a 24-h history of vesicular rash on her trunk, arms and upper legs following contact with a child with chicken 002. CASE REPORT: STATIN-INDUCED AUTOIMMUNE pox 3 weeks previously. She has a background of treatment-resistant NECROTIZING MYOPATHY WITH POSITIVE HMGCR IBD and connective tissue disorder for which she was taking ANTIBODIES adalimumab 40 mg s.c. weekly, prednisolone 10 mg OD, MTX 25 mg weekly and AZA 150 mg daily. Serology from 2010 showed immunity Bashaar Boyce1 to varicella. Initial cardiovascular, respiratory and abdominal examina- 1Rheumatology, Torbay Rheumatology Department, South Devon tions were unremarkable, she was afebrile. Blood tests showed a NHS Trust, Devon, UK lymphopenia (0.46), CRP of 10 mg/l, normal renal and liver function, serum IgG of 5 (6–16), IgA of 0.6 (0.8–2.8) and IgM of 1.3 (0.5–1.9). A Background: Statins have recently been implicated in triggering an working diagnosis of disseminated varicella with possible superadded immune related necrotizing myopathy, which requires immunosup- bacterial pneumonia was made and treatment with i.v. acyclovir and pression. Statin-induced autoimmune necrotizing myopathy is a rare oral clarithromycin (penicillin allergic) started. All immunosuppressive POSTER VIEWING I Tuesday 28 April 2015 i51

medications were stopped. Vesicles were swabbed and sent for HSV and ENT surgeons should be aware of steroid-responsive mouth PCR (negative) and VZV PCR (positive). She deteriorated clinically. symptoms as an atypical presentation of GCA. CRP rose to 140 mg/l and a repeat chest X-ray showed diffuse nodular Disclosure statement: S.L.M. is supported by a NIHR Clinician shadowing throughout both lung fields consistent with varicella Scientist Fellowship. All other authors have declared no conflicts of pneumonitis. Repeated IgG level was 4.7. Clarithromycin was interest. switched to levofloxacin following advice from microbiology and a decision was made to treat with human normal immunoglobulin as per chapter 7 of the government immunoglobulin handbook. She subse- 005. PARANEOPLASTIC GCA PRESENTING WITH VISUAL quently made a gradual improvement and was discharged 9 days after LOSS admission. She soon developed a flare of colitis requiring reintroduc- Shirish Dubey1, Holly Merris1 and Sergio Pagliarini2 tion of immunosuppressive therapy. 1 2 Conclusion: Varicella in patients with prior immunity is rare but Rheumatology, University Hospital Coventry and , patients on immunosuppressive therapy are at increased risk. Such University Hospital Coventry, Coventry, UK patients should be made aware of this possibility. Our patient may have been at increased risk because of hypogammaglobulinaemia, the Background: Patient consent was obtained. A 76 year old woman, incidence of which may be rising with increased use of combination presented to the Eye Casualty Department in April 2013, having woken DMARDS and sequential biologic therapy. Best practice following a up with tunnel vision affecting the left eye; a history of diabetes mellitus varicella contact in patients with prior immunity remains unclear. Some and hypertension. Visual acuity was 6/12 in the left eye, 6/9 in the right manufacturers of biologics (including adalimumab) advise to withhold eye with a relative afferent pupillary defect in the left eye, and the optic treatment following a significant contact. The immunoglobulin hand- disc swollen and raised nasally. Laboratory findings were: raised ESR book advises against the use of VZV-specific immunoglobulin in (67 mm/h) and CRP (17 mg/l) raised; haemoglobin 113 g/l. Temporal immunosuppressed patients with detectable antibody but to consider artery biopsy was performed next day and reported classical features the use of human normal immunoglobulin in patients with severe of GCA. The patient was started on prednisolone 60 mg daily with varicella disease in this setting. good response and referred to Rheumatology. She had had head- Disclosure statement: The author has declared no conflicts of aches for about a month prior, but thought it was migraines; also had interest. jaw claudication a few days before presentation. There was no scalp tenderness, normal peripheral pulses, carotids, right temporal artery and no gastrointestinal symptoms. She was started on aspirin and bisphosphonate. In August, steroids were gradually tapered, but she 004. CURRY-ASSISTED DIAGNOSIS IN THE was quite forgetful about taking them. Her haemoglobin dropped, so RHEUMATOLOGY CLINIC aspirin was stopped. Oesophago-gastro duodenoscopy (OGD) showed candidiasis. In September, visual aura recurred (Eye Sarah L. Donaldson1, Maura Cobine-Davies2, Ann W. Morgan3, 4 3 Casualty) and prednisolone was increased to 40 mg daily. ESR was Andrew Gough and Sarah L. Mackie 55 mm/h, CRP was <3 and haemoglobin was 88 g/l. AZA was tried, but 1Leeds Teaching Hospitals NHS Trust, 2Oral Medicine Department, 3 not tolerated. In February, she reported blurring of vision, thought to be Leeds Teaching Hospitals NHS Trust, Leeds Institute of Rheumatic worsening diabetic maculopathy. Alendronic acid was stopped as and Musculoskeletal Medicine, University of Leeds, Leeds and 4 haemoglobin was still low. CT CAP showed a complex renal cyst, but Rheumatology Department, Harrogate and District NHS Foundation results may not have been significant. Anaemia had worsened Trust, Harrogate, UK and she needed three units of blood. OGD results were okay, but colonoscopy showed a malignant tumour at the splenic flexure with Background: GCA is a systemic large vessel vasculitis (LVV) affecting adenocarcinoma on histology (Duke’s C1). In June, she underwent older people. PMR is often accompanied by subclinical GCA/LVV. extended right hemicolectomy and left partial nephrectomy (clear cell Early diagnosis of GCA is important to avoid irreversible complications Ca on histology, grade 3). She is currently undergoing chemotherapy such as visual loss, stroke and scalp or tongue necrosis. Tongue with 5-fluorouracil and is doing well. claudication and tongue necrosis are well-described but rare features Methods: We found a number of articles investigating a link between of GCA. However, mouth symptoms in GCA are not restricted to GCA and malignancy, some of which suggested negative association. tongue claudication. Two relevant articles are discussed. Methods: We report five cases of steroid-responsive mouth pain in Results: We present a population-based cohort study of malignancy PMR/GCA. risk in patients with GCA. All cases of GCA diagnosed between 1950 Results: In case 1, a 68 year old Indian woman presented with a 2- and 2004 were identified, and twice that number of matched controls week history of headache, scalp tenderness and jaw claudication. A were recruited from Rochester Epidemiology project. 204 patients temporal artery biopsy confirmed GCA. As her steroid dose was were included and 407 controls were recruited. Median follow up was reduced she experienced jaw pain, pain in her lower gums, jaw 8.1 years: there were 46 instances of malignancy in the GCA arm and claudication and tingling tongue pain causing her to stop eating spicy 76 instances of malignancy in the control arm after the index date food. In case 2, a 64 year old man presented to Rheumatology with [hazard ratio (HR) 1.26, P ¼ 0.68]. There was a suggestion of increased PMR symptoms. He had a sore tongue when eating curry which risk of colon cancer in GCA patients (HR 2.71, P ¼ 0.07). There was a resolved with steroid treatment of his PMR. In case 3, a 63 year old risk of malignancy in patients with GCA and PMR. Systematic review man presented with systemic inflammation. A diagnosis of LVV was and meta-analysis included six (five retrospective, one prospective) made following multiple hospital admissions. His main symptoms studies, including both the studies mentioned above: 39 808 patients included abdominal pain, headache, weight loss, fatigue, fevers and were included in this analysis, and the pooled risk ratio for malignancy chest pain. Interestingly, he experienced scalp pain on eating spicy in pts with GCA and PMR was 1.14. The pooled risk ratio of foods which was steroid responsive. In case 4, a 76 year old woman malignancy in the first 6–12 months was 2.16 (95% CI 1.85, 2.53) had a 5-year history of burning mouth syndrome (diagnosed by a with very little statistical heterogeneity. This meta-analysis demon- maxillofacial specialist). The soreness temporarily improved whenever strated significant cancer risk in patients with PMR and GCA, although she received short courses of steroid for a seronegative inflammatory many potential sources of bias. arthritis. She later developed biopsy-proven GCA. She has struggled Conclusion: There are some emerging data suggesting an association over the years to have symptom control when reducing steroid dose between cancer and recent diagnosis of PMR and GCA. and has continued to suffer with a steroid-responsive sore tongue. In Disclosure statement: The authors have declared no conflicts of case 15, a 61 year old woman presented with systemic inflammation, interest. jaw claudication and a red-raw tongue sensitive to spicy foods. PET- CT revealed systemic vasculitis. The mouth/tongue symptoms resolved with steroid therapy and recurred when her disease flared 006. MULTIFOCAL NECROTIZING CEREBRAL LESIONS on steroid reduction. AFTER TREATMENT WITH TOCILIZUMAB IN A PATIENT WITH Conclusion: The association between GCA and steroid-responsive RHEUMATOID ARTHRITIS burning sensations in the mouth (or capsaicin hypersensitivity) has not to our knowledge been previously reported. Capsaicin receptors Jessica L. Gunn1, Kulveer Mankia1 and Joel David1 (TRPV1) are voltage-gated calcium channels activated by heat or 1Rheumatology, Nuffield Orthopaedic Centre, Oxford, UK acidosis as well as capsaicin, and their sensitivity is upregulated by inflammatory cytokines. Their physiological role in thermoregulation Background: Tocilizumab (TCZ) is a humanized anti-human IL-6 promotes sweating. These cases highlight the importance of asking receptor mAb. Open-label extension and post marketing safety about mouth symptoms when evaluating patients with suspected analyses have suggested an increased risk of cerebrovascular GCA. Patient-reported capsaicin sensitivity might also be useful in events compared with controls but other forms of neurological injury early detection of GCA relapses. General practitioners, dentists, oral have been rarely reported. i52 Tuesday 28 April 2015 POSTER VIEWING I

Methods: We report a case of multifocal necrotizing cerebral lesions showed consistently normal BMD with T scores of –0.7, –0.6 and –0.2 occurring two weeks after the first treatment with TCZ for RA. at the lumbar spine, total hip and femoral neck, respectively. He was Results: A 61 year old man with a 5 year history of seronegative RA empirically given a 2 year trial of antiresorptive therapy with alendronic presented with acute onset, rapidly progressive, ascending lower limb acid, calcium and vitamin D but continued to fracture at least once per weakness and confusion with reduced Glasgow coma scale (GCS). He year despite a supressed P1NP. In the absence of a secondary cause had a past history of deep vein thrombosis and was heterozygous for MTX osteopathy was postulated to be the cause of his fractures and 6 factor V Leiden deficiency. He had active inflammatory arthritis and months after stopping MTX he has had no further fractures. had received his first infusion of TCZ 2 weeks previously. He had been Conclusion: Insufficiency fractures in children and adults on high and intolerant of multiple previous oral DMARDs including MTX. low doses of MTX for the treatment of cancer and inflammatory joint Adalimumab had been discontinued 8 months previously due to disease have been reported in the literature. MTX osteopathy is secondary inefficacy and alopecia universalis. Blood tests revealed described as a triad of bone pain, radiographic osteopenia and bone normal biochemistry and haematological parameters with a CRP of fracture. Small studies evaluating the in vitro and in vivo effects of MTX 14.5 mg/l which had fallen from >156 pre-TCZ. Brain CT showed on both bone formation and BMD have reached conflicting conclu- bilateral subcortical white matter hypodensities in the posterior limbic sions about the impact of MTX on bone metabolism. MTX remains a cortices and the left thalamus with a normal CT venogram. A first-line treatment in the management of inflammatory arthritis which subsequent MRI brain demonstrated multifocal necrotizing cerebral itself is a recognized independent risk factor for the development of lesions predominantly, but not exclusively, affecting the grey matter. osteoporosis. However, in patients treated with MTX who sustain Lumbar puncture revealed a raised cerebrospinal fluid (CSF) protein of recurrent insufficiency fractures in the absence of an alternative 742 mg/l with matched serum and CSF oligoclonal bands but normal explanation consideration should be given to the role of MTX in their glucose. CSF Gram’s stain, extended culture for TB and fungi and viral fracture. PCR including Toxoplasma, Nocardia, Cryptococcus, HSV, varicella Disclosure statement: The authors have declared no conflicts of zoster virus and enterococcus were negative. Blood cultures and interest. extended serum viral serology were also negative. A brain biopsy of the necrotizing lesions showed a haemorrhagic and thrombotic 008. SYPHILIS THE VASCULITIS LOOK-ALIKE microangiopathy preferentially affecting the small vessels of the cerebrum with no organisms and no growth. Treatment consisted of Muhammad F. Kazmi1 empirical broad spectrum antibiotics followed by i.v. methylpredniso- 1Department of Rheumatology, Royal Hallamshire Hospital, Sheffield, lone and a tapering regimen of oral steroids. Eight weeks post UK presentation there was MRI evidence of partial resolution of the necrotizing lesions and the patient continues to make a good Background: Tertiary syphilis can mimic many diseases as it causes functional improvement. multi-system manifestations and still remains one of the great although Conclusion: We describe the first reported case of necrotizing somewhat forgotten mimics of primary systemic vasculitis. Conditions cerebral lesions occurring in a patient treated with TCZ. Neurological which involve various systems can be challenging to diagnose and injury has previously been described in patients treated with TCZ for manage due to varied clinical features and possible differential RA including leucoencephalopathy after 40 months of TCZ therapy diagnoses include systemic vasculitis. Vasculitis can be primary or and limbic encephalitis associated with glutamate receptor antibodies secondary due to various medical conditions including infections; after three infusions. In both cases, clinical and MRI abnormalities differentiation between the two is very important as immunosuppres- persisted despite discontinuation of TCZ and, in one case, despite sion in vasculitis look-alikes can be potentially harmful. Thus, when high-dose CS. In contrast, our patient developed multifocal cerebral considering a possible diagnosis of vasculitis, rheumatologists need to lesions after a single TCZ infusion but experienced clinical and keep an open mind, this case illustrates this and the importance of radiological recovery after discontinuation of TCZ and with CS therapy. excluding infection as many clinical and laboratory features are This case highlights the potential for early neurological injury but common to both vasculitis and infection but treatment remains very subsequent recovery with prompt drug discontinuation. different. Disclosure statement: The authors have declared no conflicts of Methods: We report the case of tertiary syphilis in a 48-year-old interest. Caucasian man who presented with constitutional features including arthralgia, myalgia, tiredness, red painful eyes along with high ESR and CRP and significant proteinuria. He had background of significant 007. RECURRENT INSUFFICIENCY FRACTURES IN aortic regurgitation detected 2 years ago which was investigated by LONGSTANDING RHEUMATOID ARTHRITIS: THE RESULT OF cardiologists and was awaiting elective aortic valve replacement. He METHOTREXATE OSTEOPATHY? sought his general practitioner’s attention with few months history of constitutional symptoms and was found to have persistently elevated 1 2 1 Jessica L. Gunn , Alan Steuer and Kassim Javaid inflammatory markers and was anaemic, hence was referred to the 1 Rheumatology, Nuffield Orthopaedic Centre, Oxford and Rheumatology Clinic. He had felt tired, achy and was having recurrent 2 Rheumatology, Wexham Park Hospital, Slough, UK episodes of episcleritis. He denied any infective symptoms, weight loss or skin rash. General examination detected cardiac murmur but Background: MTX osteopathy is infrequently reported as a cause of otherwise unremarkable with no joint inflammation detected. bone fracture in patients receiving this drug for inflammatory arthritis. Results: Blood tests showed normocytic normochromic anaemia with However, this is not widely known and may be under-recognized as a CRP levels of 82 mg/dl and ESR of 105 mm/h, multiple blood cultures clinical entity. were negative with no vegetations on transthoracic echocardiogram, Methods: We present a case of recurrent stress fractures attributed to urine dipstick showed þþþ of blood and protein and proteinuria of MTX osteopathy, in a patient with longstanding RA. >1 g was detected, HIV test and immunoglobulin levels were normal. Results: An 84 year old male with a 14year history of seropositive Further workup showed plasma ANCA was positive with negative MPO nodular RA experienced recurrent spontaneous stress fractures, and PR3, ANA was negative and PET-CT showed no evidence of affecting the calcaneum, ankle, distal femur and proximal tibia, over aortitis or any collection. Syphilis serology Trep IgM and VDRL was a 6 year period. He had a background of previous transient ischaemic positive consistent with active infection; genitourinary medicine clinic attacks and basal cell carcinoma. His RA had been managed confirmed diagnosis of tertiary syphilis. He was also reviewed in eye predominantly with MTX monotherapy (15 mg once weekly) since and renal clinics, where episcleritis and proteinuria was found to be diagnosis and his disease was in a low activity state for at least the consistent with syphilis infection. Treatment was started with penicillin preceding 5 years. He required infrequent intramuscular glucocorti- and subsequently CRP settled with improvement in symptoms. coids early in his disease but had no exposure to oral glucocorticoids. Conclusion: This case highlights this relatively forgotten disease He is a lifelong nonsmoker, consumes <2 units of alcohol/ day and has which because of its heterogeneous manifestations mimics other an estimated dietary calcium intake of 400 mg/day. Investigations diseases and hence holds the sobriquet of the Great Masquerader. revealed a normal bone profile, ALP at the lower end of the normal Rheumatologists see numerous conditions with systemic involvement, range despite fracture and creatinine of 116 mmol/l. The following but it can be very useful to consider syphilis in the differential diagnosis results were all within normal limits: serum immunoglobulins, serum of systemic vasculitis as it can cause cardiovascular, renal, skin, lung and urine electrophoresis, 25(OH)D3 >50 nmol/l, parathyroid hormone, and ocular features. serum lead level, anti-tissue transglutaminase antibodies, testosterone Disclosure statement: The author has declared no conflicts of and TSH and 24-h urinary cortisol, calcium and amino acids. DXA interest. POSTER VIEWING I Tuesday 28 April 2015 i53

009. EOSINOPHILIC FASCIITIS SECONDARY TO were negative as was QuantiFERON gold testing; HIV and viral RANIBIZUMAB INJECTIONS serology were negative. His echocardiogram, CT chest, abdomen and pelvis and ultrasound of urinary tracts all found no abnormalities. His Haroon Khan1, Kuranageri Poornesh2 and Richard A. Watts1 1 2 ANCA, ANA, ANA to Hep-2 cells, ENA, complement, RF and Rheumatology, Ipswich Hospital NHS Trust and Ophthalmology, immunoglobulins were normal. He was also seen by haematology Ipswich Hospital NHS Trust, Ipswich, UK who performed a bone marrow biopsy which returned morphologically normal with no evidence of malignant cells. He went on to have a white Background: EF is a rare disorder characterized by fasciitis and cell hexamethylpropyleneamine oxime whole-body scan which peripheral eosinophilia; it is differentiated from scleroderma by the showed slightly increased uptake in the left side of his manubrium; pattern of skin involvement with sparing of the digits, fascial sparing of this raised a suspicion of an inflammatory arthropathy, prompting dermis and absence of RP. It can be regarded as scleroderma-variant referral to rheumatology. Blood samples were sent to the National with progression to scleroderma in some cases. It has been postulated Amyloid Centre on suspicion of an systemic autoinflammatory that the disturbed vascularization found in scleroderma skin is due to syndrome. Results confirmed a new mutation in the region of the reduced expression of the potent angiogenic factor vascular endothe- TRAPS gene TNFRSF1Aex4-5 C96Wc.375T>G. This is a new lial growth factor (VEGF). We report a case of EF, possibly secondary mutation was not previously reported in the literature. During this to the use of ranibizumab intravitreal injection (anti-VEGF mAb) for wet period, his son was admitted with pyrexia, abdominal pain and age-related macular degeneration (AMD). elevated inflammatory markers. Abdominal CT revealed no abnorm- Methods: A 72 year old woman receiving intravitreal injections of ality. Given his father’s history of TRAPS, he too was tested and found ranibizumab for wet AMD presented with a history that 6 months to be positive for the TRAPS mutation. previously she had received her first injection of ranibizumab after Conclusion: Currently, he receives 0.5–1 mg/kg prednisolone for which she noticed swelling of her legs and forearms. After the second acute attacks which settle within 5 days. If, however, he starts to injection, the swelling increased and spread from feet to thighs. The require more than 10 days of treatment or if his annual mean dose of treatment was suspended, with gradual settling of swelling but she prednisolone is >5 mg/day he will require anakinra. His inflammatory was left with very tight skin over her forearms with loss of movement at markers have remained normal between attacks to date and he has no wrists and flexion deformities of her fingers developing an early prayer evidence of amyloid. sign. She had tight skin over her feet, calves and thighs with some Disclosure statement: The authors have declared no conflicts of residual lumpiness. There were no symptoms or signs of RP. There interest. were no telangiectasiae, sclerodactyly or mucosal involvement. She was not taking any regular medications including health supplements. She was treated with prednisolone 20 mg daily and Mycophenolate 1 g 011. ADULT ONSET STILL’S DISEASE IN PREGNANCY daily had regular monitoring blood tests and was reviewed monthly. At Mark Leith1 and Auleen Millar1 follow up after 3 months she reported feeling well in herself, was 1Rheumatology, Antrim Area Hospital, Antrim, UK walking long distances and experienced no further spreading of skin tightening. She is maintained on 20 mg prednisolone and 2.5 mg daily Background: There have been 14 cases reported to date which dose of MMF and 9 months after the initial injections of ranibizumab describe the onset of adult onset Still’s disease (AOSD) during she received two further intravitreal injections as her sight was pregnancy. There is therefore a lack of evidence for safe, effective deteriorating with no worsening of her condition. treatment in pregnant women. Most cases have used prednisolone Results: There was evidence of normochromic anaemia, eosinophilia monotherapy, but methylprednisolone, HCQ and IVIG have also been (1.9 109), thrombocytosis, polyclonal increase in immunoglobulins used. There is one case report of anakinra used to induce and maintain IgG (58.7 g/l) with elevated ESR (102 mm/h) and CRP (56 mg/l), ANA remission in pregnancy with no harmful effects to the fetus. and ANCA negative, ENA positive for Ro but negative for ScL70. Her Methods: We present the case of a 31 year old para 0 woman of 22 albumin was low but with normal liver function, renal function tests weeks gestation who presented to a district general hospital with a with negative serum free light chain analysis. There was no evidence of 1 week history of a pruritic rash, pyrexia, arthralgia and pharyngitis pulmonary fibrosis on high-resolution CT scan of the chest, pulmonary after returning from her honeymoon in Greece. function tests and echocardiography were normal with no evidence of Results: The patient had previously been entirely well. She was also pulmonary hypertension profoundly needle phobic. Blood and urine cultures and extensive Conclusion: EF is a rare disorder, the cause of which remains virology screen including parvovirus, CMV, EBV, HAV, HBV, HCV and unknown. We consider that in this woman’s case it was possibly enterovirus all returned negative. Vaginal and throat swabs were triggered by the use of ranibizumab, an inhibitor of VEGF. negative. Malaria screen was also negative. Lyme serology revealed a Disclosure statement: The authors have declared no conflicts of positive IgM but negative IgG, and after discussion with microbiology/ interest. virology it was felt this was likely to be a false-positive IgM result. ANA and RF were negative, but she was found to have elevated alanine transaminase, ALP and GGT at the time of presentation. Her ferritin 010. A NEW GENETIC MUTATION IN TNF RECEPTOR- returned at 3000 ng/ml and having fulfilled the Yamuguchi criteria with ASSOCIATED PERIODIC SYNDROME a lack of other causes she was started on 30 mg prednisolone with dramatic improvement initially. After 3 days, however, her rash and Mark Leith1 and Auleen Millar1 pyrexia returned. It was accompanied by worsening liver function tests 1Rheumatology, Antrim Area Hospital, Antrim, UK (LFTs) and a climbing ferritin. USS abdomen was normal but ECG confirmed a small pericardial effusion. Prednisolone was subsequently Background: We present the case of a family with a new diagnosis of increased to 70 mg daily. After initial improvement, prednisolone was TNF receptor-associated periodic syndrome (TRAPS). The father, a slowly reduced to 50 mg but unfortunately she flared with elevated 59-year-old man with a history of type 2 diabetes mellitus and ferritin and LFTs and rash. The option of anakinra was discussed with hypertension had presented to a district general hospital on numerous the patient, but she declined due to the needle phobia. She was occasions since 1990 with recurrent pyrexic episodes associated with therefore started on AZA 50 mg. Unfortunately, she developed a florid rigors, fatigue and arthralgia. This had often been attributed to a lower drug reaction within 1 week and was admitted with worsening rash and respiratory tract infection, despite a lack of positive culture results or pyrexia which resolved on withdrawal of AZA. Prednisolone was chest X-ray changes to support this. He was entirely well between increased to 1 mg/kg and reduced more slowly over the following episodes. weeks and her disease remained in remission throughout the Methods: He had travelled extensively over the years but had remainder of her pregnancy. Her only treatment induced side effects previously tested negative for malaria and other tropical diseases. were a mildly raised BM of 8.9. She delivered a healthy baby girl at His ESR and CRP were elevated with each flare, but had not been 38 weeks on 12.5 mg prednisolone. In her post-partum period she checked during asymptomatic periods. He was extensively investi- managed to reduce prednisolone to 7.5 mg when unfortunately her gated during each admission, but multiple blood urine and sputum symptoms returned. She is currently considering anakinra treatment culture findings were negative. which may be safer if future pregnancies are considered. Results: He was admitted again in August 2013 with a 4-week history Conclusion: Tocilizumab has good evidence for use in AOSD but is of pyrexia, rigors and elevated inflammatory markers with a CRP level associated with risk of spontaneous abortion and embryo-fetal death. of 150 mg/l and an ESR of 111 mm/h and a leucocytosis of 11.7 x 109/l. Disclosure statement: The authors have declared no conflicts of Ferritin was elevated at 1700 ng/ml on this occasion, but he met no interest. other Yamaguchi criteria for Still’s disease. Blood and urine cultures i54 Tuesday 28 April 2015 POSTER VIEWING I

012. HALO NAEVI, VITILIGO AND DIFFUSE ALOPECIA showed sterile haematuria. He had positive ANCA and PR3 titre of AREATA ASSOCIATED WITH TOCILIZUMAB THERAPY 4.1 IU (0–0.9), which was consistent with GPA. His skin biopsy showed Wegener’s granuloma. His chest X-ray and subsequent CT chest Kavitha Nadesalingam1, Mark Goodfield2 and Paul Emery1 1 2 confirmed cavitating lung lesions. Further investigations included MRI Rheumatology and Dermatology, Chapel Allerton Hospital, Leeds, of the prostate gland that showed inflammation in his seminal vesicles UK and prostate gland. MRI of the brain that revealed no meningeal involvement, but there was extensive opacification in his paranasal Background: We present a follow-up case report of a 33 year old sinuses with absence of the nasal septum. Due to the patient’s fertility woman with juvenile onset arthritis who developed halo naevi and needs, rituximab was chosen over CYC as per NHS England policy as subsequent vitiligo and alopecia areata while on tocilizumab therapy. an induction regimen along with methylprednisolone and then MTX as Methods: Having failed to respond to conventional DMARDS and maintenance therapy. His prostatitis symptoms improved initially, but multiple anti-TNF therapies, the patient was commenced on tocilizu- further relapses were treated with oral steroids. mab. Three years later she went on to develop recurrent abscesses Conclusion: This is a case of GPA presented with prostatitis and skin requiring drainage. Swabs confirmed methicillin-resistant granuloma. Urogenital tract involvement in GPA is rare. In a large case Staphylococcus aureus (MRSA) and Panton-Valentine Leukocidin series of 174 GPA patients, the incidence of urogenital tract (PVL) positivity. Tocilizumab was withheld for 6 months while the involvement was 2.3%. Along the urogenital tract, the prostate is the abscesses healed. On recommencing tocilizumab, the patient devel- most commonly affected, then followed by seminal vesicles and oped halo naevi at the site of every naevus on her body. Malignant epididymis. Prostatitis in GPA can lead to urinary frequency, dysuria, melanoma was excluded. Tocilizumab was withheld briefly but haematuria and urinary retention. This case report aims to raise restarted for disease control and the patient went on to develop awareness among rheumatologists that urogenital tract involvement is patches of vitiligo on her torso. Therefore, tocilizumab was discon- under-recognized in GPA. To prevent avoidable complications such as tinued and treatment switched to abatacept. On discontinuing urinary retention and strictures, it is essential to seek urology input tocilizumab there was no further progression of depigmentation. early on. However, having failed abatacept, tocilizumab was restarted Disclosure statement: The authors have declared no conflicts of 18 months later; after 6 months of therapy, the patient reported loss interest. of eye lashes, eye brows and hair. A diagnosis of diffuse alopecia areata was made. Results: This is the first case to describe the development of vitiligo and diffuse alopecia areata secondary to tocilizumab therapy. The 014. RHEUMATOLOGISTS BEWARE, RHEUMATIC FEVER aetiology of these conditions is unclear. IL-6 concentrations have been REMAINS PREVALENT: A CASE OF ACUTE RHEUMATIC found to be significantly higher in patients with vitiligo and IL-6 can FEVER induce the expression of ICAM-1 on melanocytes, thereby facilitating 1 1 1 leucocyte-melanocyte attachment and immunological cytotoxicity. Arvind Nune , Stephanie Ling , Rachel Gorodkin , 2 2 Tocilizumab therapy blocks IL-6R, thereby inhibiting the consumption Andreas Hoschtitzky and Petra Jenkins 1 2 of IL-6 by normal receptors leading to an increase in serum IL-6. This Kellegren Centre for Rheumatology and Manchester Heart Centre, increase in IL-6 could therefore act systemically and have a direct Manchester Royal Infirmary, Manchester, UK effect on melanocytes. The role of IL-6 in alopecia areata is less well documented although higher levels have been found in patchy Background: We present a case of a young woman with ARF to raise alopecia areata. There have been case reports of diffuse alopecia awareness that rheumatic fever remains prevalent in the UK. areata occurring following anti-TNF therapy and chemotherapy and Methods: A 17-year-old British-born Indian woman presented to the the pathogenesis is likely to involve a T cell autoimmune mediated Manchester Royal Infirmary at the beginning of December 2013 with process triggered by an endogenous or exogenous stimulus which polyarthritis, fever, exertional breathlessness epistaxis and abdominal sustains an inflammatory reaction leading to hair loss. Cross-reacting pain. antigens from infecting organisms may be implicated in vitiligo and our Results: Her initial blood results revealed a CRP of 240 mg/dl (0–10) patient only developed depigmentation on resuming treatment follow- and an ESR of 120 mm/1st hour (<15). Her renal function was normal. ing infection with MRSA with PVL positivity. This infection may have She experienced several temperature spikes over 388C. Her ECG been significant in the development of her symptoms in combination revealed severe aortic and mitral regurgitation without any vegetations. with the cytokine disturbances created by tocilizumab. She was initially treated for infective endocarditis with i.v. antibiotics to Conclusion: This case report is important in the pathogenesis of halo cover highly virulent Staphylococcus aureus. Despite the prolonged naevi, vitiligo and diffuse alopecia areata, and supports previous antibiotics, there was no improvement in the patient’s condition or theories on cellular and humoral immunity as causative factors. The inflammatory markers. Our opinion was sought to rule out any regression of melanocytes during treatment with tocilizumab could rheumatological cause for her illness. On further questioning, she also implicate IL-6 and serum IL-6R as future targets in the treatment had suffered several episodes of tonsillitis 4 weeks prior to admission of melanoma through its direct effect of melanocytic cytotoxicity which and her general practitioner had treated her for pharyngitis. She had supports previous studies. recurrent epistaxis and urticarial skin rashes on her limbs. There was Disclosure statement: P.E. has received consulting fees from AbbVie, no convincing evidence for any rheumatological condition and her CTD BMS, Merck, Pfizer, Roche, Takeda and UCB; and has received screen was negative. Several blood cultures were negative for any research grants from AbbVie, BMS, Merck, Pfizer, Roche and UCB. All fastidious organisms. The combination of epistaxis, polyarthritis, skin other authors have declared no conflicts of interest. rashes and aortic regurgitation in a teenage girl with recent pharyngitis led us to suspect ARF. Her anti-streptolysin O antibody was positive with a titre of 400 IU/ml (0–200). She had a successful aortic valve 013. PROSTATITIS, AN UNCOMMON PRESENTATION OF replacement. Histopathology of the aortic valve showed Aschoff GRANULOMATOSIS WITH POLYANGIITIS bodies, which are pathognomonic of rheumatic fever. She is now stable on lifelong penicillin prophylaxis. Arvind Nune1, Laura R. Newton1, Anna Goodheart2 and Ian Bruce1 Conclusion: Our patient met the revised Jones criteria for ARF. For 1Kellgren Centre for Rheumatology, Manchester Royal Infirmary and diagnosis, either two major, or one major and two minor features are 2Manchester Royal Infirmary, Manchester, UK needed, and our patient had arthritis and carditis as major features with evidence of group A streptococcal infection. Epistaxis was a Background: Granulomatosis with polyangiitis (GPA; Wegener’s minor criterion in the original Jones criteria in 1944, but to improve granulomatosis) is a systemic vasculitis with a predilection for small specificity, this was not included in revised criteria. Epistaxis can be to medium vessels. It most commonly affects the upper respiratory the initial complaint in up to 5% of ARF cases; this is due to vasculitis tract and also involves the skin and lungs. Though kidney involvement and a functional platelet defect as part of an autoimmune process. The is not uncommon, it usually spares the urogenital tract. Untreated, it key learning point from this case is that arthritis is the most common has a high mortality hence the importance of prompt diagnosis and manifestation of ARF, and in a patient with polyarthritis in the early treatment. appropriate clinical context, we must think of ARF as a differential. Methods: A 31 year old Caucasian man was admitted to the Kellgren Even though ARF is most common among school-aged children, it can Centre for Rheumatology at the end of 2013 with a 3-month history of still occur in young adults. According to a recent worldwide painful and difficult micturition with urethral bleeding, ulceration of the epidemiological study, incidence of RF is around 1 per 100 000 in chest wall and headache. He had ongoing fatigue with exertional UK. We feel it is under-diagnosed and due to recent outbreaks of breathlessness but denied haemoptysis. group A streptococcal infections, the incidence of rheumatic fever is Results: On admission, his inflammatory markers were elevated with rising and we should be vigilant. CRP 220 mg/l (0–10), ESR 118 mm/1st hour and white cells 17.5.(4–11) Disclosure statement: The authors have declared no conflicts of His kidney function was normal and a mid-stream specimen of urine interest. POSTER VIEWING I Tuesday 28 April 2015 i55

015. MYCOBACTERIUM MARINUM MIMICKING ACUTE onset of her rash. After her second cycle of CYC she became septic INFLAMMATORY ARTHRITIS and unwell with worsening of rash and necrosis. She received a further three cycles of plasma exchange and her leg ulcers showed marked Aidan O’Neill1, Julie-Ann Henderson1, David Alderdice2, 3 1 improvement. She completed a six cycle course of i.v. CYC pulses. Claire Donnelly and Andrew Cairns Maintenance treatment with infliximab and MMF is planned following 1Rheumatology, Musgrave Park Hospital, Belfast, 2Dermatology, 3 further skin grafting. Lagan Valley Hospital, Lisburn and Infectious Diseases, Royal Results: There are no randomized controlled trials regarding plasma Victoria Hospital, Belfast, UK exchange in Behc¸ et’s disease. There are occasional case studies and case reports available in the literature. Plasma exchange has shown to Background: A 60 year old male aquarist was referred to be effective in necrotizing vasculitis in Behc¸ et’s disease. It is also Rheumatology with a 4 month history of swelling of his left thumb useful for mucocutaneous manifestations of Behc¸ et’s disease. Plasma interphalangeal joint, metacarpophalangeal (MCP) joints, wrist and exchange therapy has been used for ocular lesions in conjunction with elbow. He received multiple courses of antibiotics for presumed CS and immunosuppressants. Plasma exchange is also useful for oral cellulitis, with inadequate response. Nodulocystic, crusting lesions and genital ulceration with disabling gynaecological lesions in Behc¸ et’s were noted on the dorsum of his left hand and elbow with synovitis of disease. his left elbow, left wrist and left fourth MCP joint. This was confirmed Conclusion: Our case supports the use of plasma exchange in severe on musculoskeletal ultrasound, with positive power Doppler signal. He Behc¸ et’s disease with necrotizing vasculitis which is resistant to the had no significant past medical or family history. Initial blood tests standard immunosuppressive treatment. We suggest plasma showed white cell count 6.9, ESR 2 mm/h, CRP of 2.5 mg/l and RF, exchange should be added to the long lists of treatments for anti-CCP antibody and ANA negativity. Urate, complement and Behc¸ et’s disease including topical and systemic steroids, antibiotics, immunoglobulins were normal. X-rays showed an olecranon bursitis, immunosuppressive and anti-inflammatory agents. minor osteoarthritic changes and no erosions. A swab of the lesion Disclosure statement: The authors have declared no conflicts of over his fourth MCP cultured Staphylococcus aureus. interest. Methods: He was commenced on flucloxacillin given the culture finding, referred to Dermatology and a MRI of his left wrist and elbow was arranged. Elbow MRI showed a significant joint effusion with 017. HARLEQUIN ICHTHYOSIS AND INFLAMMATORY synovitis of the ulnohumeral and radio-capitellar joints, with articular ARTHRITIS: CASE REPORTS OF A VERY RARE COMBINATION cartilage thinning and sub-chondral oedema. Wrist MRI showed Subhra Raghuvanshi1, Jonathan Pinnell1 and Tanya Potter1 marked synovitis of all of the intra-carpal, radio-carpal and distal 1Rheumatology, University Hospitals of Coventry and Warwickshire, radio-ulnar joints, with peri-articular erosions and intraosseous Coventry, UK oedematous changes. These findings were in keeping with ongoing inflammatory arthritis. Dermatology performed a punch biopsy which Background: We would like to share two cases with combination of confirmed the presence of non-caseating granuloma and multi- harlequin ichthyosis (HI) and JIA. Harlequin Ichthyosis has prevalence nucleated giant cells. Culture confirmed mycobacterium marinum of 1/1000 000 and incidence of 5 births/ year in the UK with an overall and he was commenced on minocycline. survival rate of 56%. The molecular pathogenesis includes hyperker- Results: Rheumatology review after 3 months confirmed the skin atinosis of skin resulting in significant contractures with fixed flexion lesions and arthralgia had markedly improved. There was no clinical deformities and underdevelopment with short stature besides other synovitis on examination of his wrist, MCP joints or elbow. He was clinical features. It is linked to ABCA12 mutation but heterozygous reviewed by infectious diseases 6 months post-clinical resolution, 9 mutation, Oral retinoids and advanced medical management had led months into minocycline treatment. He had suffered no relapse and to increased survival. Thus, unfolding varied rheumatological manifes- antibiotics were stopped. tations which adolescent rheumatologists are more likely to encounter Conclusion: Mycobacterium marinum is an atypical mycobacterium in future. found in fresh and saltwater. It is commonly referred to as Fish Tank Methods: In case 1, a 30 year old woman with diagnosis of HI since Granuloma. Skin infection is the most common initial presentation, but birth and rickets as a child was referred to musculoskeletal services in invasive infection can occur. Osteomyelitis, septic arthritis and 2002 with ongoing painful elbows, shoulders, fingers and locking of septicaemia are a less common but severe consequence of infection. wrists for few years. On examination, symptoms suggestive of Those on immunosuppressive treatment are more likely to develop impingement with marked restriction of joint movements with fixed these sequelae. This patient’s presentation mimicked an inflammatory flexion deformities of fingers were noted. Radiographic features arthropathy and highlights the importance of taking a detailed history, included significant destructive changes around wrist with subluxation including occupation and recreational interests. Excluding infective of proximal row of carpal bones. An MRI scan of shoulder revealed causes of inflammatory arthritis is vital when immunosuppressive rotator cuff tendinopathy and small joint effusion but no synovitis. She treatment can have potentially disastrous consequences. remains seronegative and is currently being managed by intensive Disclosure statement: The authors have declared no conflicts of physiotherapy, splints and intra-articular injections. To the best of our interest. knowledge, she is the longest known survivor of this condition in the world and surely in the UK. In case 2, a 22 year old man with HI was 016. PLASMA EXCHANGE IN BEHC¸ ET’S DISEASE seen in our adolescent rheumatological services since age of 16. He was diagnosed with JIA in Addenbrooke’s, Cambridge and his Manivannan Prathapsingh1 and Sara Carty1 1 inflammatory arthritis was managed in early years with MTX. He was Rheumatology, Royal Gwent Hospital, Newport, UK soon commenced on etanercept at 25 mg/ week which revolutionized his inflammatory arthritis and he no longer needed a wheelchair to Background: Plasma exchange offers the quickest short-term answer mobilize. He was subsequently tried on adalimumab, MTX and is by removing harmful autoantibodies and immune complexes in currently on LEF. He has reported worsening of his skin condition with Behc¸ et’s disease. cracks and increased skin infections with all previous DMARDs and Methods: A 67 year old woman who initially presented generally biologics and his management remains a clinical challenge. unwell with multiple purpuric vasculitic areas involving hard palate, Results: To the best of our knowledge three cases of inflammatory nose, face, flanks and limbs. The lesions became necrotic and large arthritis with HI have been reported in literature, our male patient being areas of tissue were lost. She also developed swelling of the left orbit one of them (Clements et al). Little has been researched about with proptosis. She was treated with broad spectrum antibiotics for biochemical changes in inflammatory cytokines in patients with HI, presumed infection within the left eye. Her initial ophthalmology review certainly a mouse model with overexpression of IL-37 hypothesizing suggested uveitis complicating vasculitis and she was treated with i.v. inflammation as contributor to HI. methylprednisolone pulses. She was then treated with three cycles of Conclusion: Even little is known about management of inflammatory plasma exchange and i.v. CYC pulses. A diagnosis of probable arthritis in patients with HI and effects of conventional DMARDs and Behc¸ et’s was made on the basis of pathergy, vasculitis, uveitis and biologics on dermatological manifestations. With increasing life oral ulceration. She had plastic surgical input for wound management expectancy in HI we can expect to see an increase in metabolic and skin grafting. She also had left orbital extraction as her eye could bone disorders, increased degenerative joint disease and indeed more not be saved. Then she developed deep vein thrombosis in right leg of inflammatory arthritis which will pose a diagnostic and management and treated with warfarin. She was discharged home after a period of challenge. rehabilitation and remained reasonably well on prednisolone and AZA. Disclosure statement: The authors have declared no conflicts of Nine months after this episode, she had a relapse of her vasculitis in interest. her foot with ulceration and i.v. CYC was restarted within 2 days of the i56 Tuesday 28 April 2015 POSTER VIEWING I

018. PARANEOPLASTIC PALMAR FASCIITIS AND uncommon to see SLE patients on CS as a part of their treatment POLYARTHRITIS SYNDROME: RECOGNITION AND regime and so correct attribution of aetiology of this presentation is a TREATMENT vital part of management. 1 2 Methods: We report a case of acute necrotizing pancreatitis due to Fiona Rayner and Iain Goff SLE and review of the literature to clarify the impact of steroid use in 1Rheumatology, University Hospital of North Durham, Durham and 2 such cases. Rheumatology, Northumbria NHS Foundation Trust, North Results: A 37 year old woman of African ancestry with SLE diagnosed Tyneside, UK in 2006 (positive ANA, dsDNA, nephritis, arthritis) presented with acute abdominal pain, nausea and vomiting in July 2014. At the time of the Background: Palmar fasciitis and polyarthritis syndrome (PFAPS) is a admission, she was maintained on MMF 2.5 g/day, prednisolone rare but recognized paraneoplastic phenomenon first reported in 10 mg/day, HCQ 400 mg/day and belimumab which had been association with ovarian cancer. It is characterized by joint pains commenced 11 months prior, to control her active arthritis and skin predominantly in the hands, swelling of the fingers, palmar fascial rashes. Amylase was elevated to 468 U/l (20–100), ESR 70 mm/1st thickening and flexion contractures. The pathogenesis of PFAPS is not hour (0–7) and dsDNA 81 IU/ml (0–13.9). Abdominal ultrasound well understood but due to the strong association with gynaecological demonstrated no gallstones and she did not drink alcohol. A diagnosis malignancies it is thought to be related to hormonal alterations. of acute pancreatitis was made. She initially improved with supportive Methods: We describe a 59-year-old woman who was referred to treatment including i.v. fluids, analgesia but had two subsequent Rheumatology with a 15-month history of joint pains and stiffness. She admissions within the next 8 weeks with recurrent pancreatitis. CT had a past medical history of primary peritoneal cancer, treated with scan of the abdomen revealed pancreatitis with 20% necrosis. An surgery and chemotherapy, and deemed to be in remission. Joint SLE-induced pancreatitis was suspected having ruled out other symptoms commenced one month into her chemotherapy (carboplatin causes and treatment with i.v. hydrocortisone 80 mg BD followed by and paclitaxel), and were initially thought to be drug side effects; onset oral prednisolone 40 mg OD was instituted with a significant clinical was in her hands and subsequently both hips, knees and shoulders. and biochemical improvement. A follow-up CT scan showed improve- She developed flexion contractures of the hips and knees, and bilateral ment of her pancreatitis and she has subsequently been changed to restricted shoulder movement. Physical examination revealed multiple rituximab to enable better disease control. Our Medline search used smooth, firm, tender swellings on the palms of both hands with the key words acute pancreatitis and SLE and we identified five case overlying purple discoloration, flexion deformities of the knees and series on SLE and acute pancreatitis that included 86 cases. Of these, hips and reduced range of movement at both shoulders in a capsular the majority (70 out of 86) were in the context of active SLE. 58 of the pattern. There was no significant small or large joint synovitis. Serology 86 had either an increase or initiation in steroids as part of their revealed a weakly positive RF but negative ANA, ENA and anti-CCP treatment regime for acute pancreatitis and 20 had their steroid dose antibodies. Inflammatory markers were normal and X-rays showed maintained during the illness (Table 1). early OA of hips and knees. CA125 was raised at 104 and the Conclusion: Pancreatitis needs to be considered in patients with SLE oncologists were contacted regarding possible tumour recurrence. presenting with acute abdominal pain. While steroids are implicated in Results: Based upon clinical features a diagnosis of PFPAS was pancreatitis in the general literature, our case review shows that a high made. She was managed with a combination of intra-articular steroid proportion of cases in SLE are associated with active disease and injections to the shoulders and knees, physiotherapy to improve her therefore an increase in steroid therapy is actually indicated. range of movement and occupational therapy. The patient was Disclosure statement: The authors have declared no conflicts of unexpectedly admitted to hospital with headache and diplopia and a interest. posterior fossa lesion was discovered. Further investigation revealed widespread thoracic and abdominal lymphadenopathy, and she was diagnosed with recurrence of the cancer. Her cerebral metastasis was 020. HYDROXYCHLOROQUINE INDUCED CARDIOTOXICITY: treated with i.v. dexamethasone at a dose of 16 mg daily, and A RARE COMPLICATION OF A COMMON DRUG subsequent successful neurosurgical resection. Further rheumatology Maliha Shaikh1, Aditi Chitale1 and Richard Stratton1 review revealed the palmar tendon lumps had resolved. Her joint 1Rheumatology, Royal Free Hospital, London, UK contractures remained, but without significant pain. Conclusion: PFAPS is rare with no specific diagnostic test. It should Background: CTDs can cause myocarditis, often reflecting disease be considered in patients with a previous malignancy, although it may activity, and this needs to be differentiated from treatment-related side precede the diagnosis of cancer, and may present with musculoske- effects. HCQ-induced cardiotoxicity is rare, with 42 definitive cases letal symptoms in the first instance. There are no guidelines for published, predominantly in SLE or RA patients and one in treatment of PFAPS, although eradication of the cancer generally scleroderma. We report HCQ-induced dilated cardiomyopathy in a provides improvement. Patients seem to respond symptomatically to woman with SS. immunosuppression, in this case with IA steroid injections, and Methods: A 52 year old woman of Iraqi origin presented with a week’s subsequent high-dose dexamethasone. It seems reasonable to treat history of dyspnoea at rest, palpitations, chest tightness, dry cough these patients with steroids and use intensive physiotherapy and and peripheral oedema (New York Heart Association class IV) on a occupational therapy to manage their symptoms. background of 3 months of progressive dyspnoea. Recently a Rapid Disclosure statement: The authors have declared no conflicts of Access Chest Pain clinic had diagnosed non-cardiac chest pain and interest. an outpatient ECG showed mildly enlarged left ventricle with normal wall thickness, severe global hypokinesis, an ejection fraction <25%, 019. ACUTE NECROTIZING PANCREATITIS IN SLE: A CASE estimated systolic PA pressure 42–47 mmHg and moderate biatrial REPORT AND LITERATURE REVIEW enlargement. Her previous ECG had been normal. SS had been diagnosed 4 years previously: sicca symptoms, arthralgia and Hem R. Sapkota1, Ellen Bruce1, Arshad Sathathulla1, Jayne Little1 abnormal parotid glands on ultrasound with raised ESR and CRP and Ian Bruce1 (ANA 1/1000, fine speckled, anti-Ro, anti-La and RF positive), HCQ 1Kellgren Centre for Rheumatology, Central Manchester University 400 mg daily was commenced. There was no history of major organ Hospital, Manchester Royal Infirmary, Manchester, UK involvement. Results: She had basal crackles, normal heart sounds, 8 cm raised Background: Acute pancreatitis is a rare manifestation of SLE. CS are JVP and mild bilateral ankle oedema. Troponin, full blood count, urea commonly implicated as a risk factor for acute pancreatitis. It is not and electrolytes, liver function tests and CRP were normal. Chest X-ray

019 TABLE 1. Acute pancreatitis in SLE: steroid use and outcome in case series Authors Cases, n Active Steroid use Outcome disease on diagnosis, % Increased/ Maintained, n Decreased, n Stopped or Recovery, n Death, n initiated, n none, n Reynolds et al. 20 80 9 10 1 — 19 Unclear Derk et al. 25 76 18 5 — 2 18 (on steroid) 4 Ben Dhaou et al. 6 100 6 — — — 5 1 Yang Y et al. 27 100 16/1 5 4 1 17 10 Saab et al. 8 25 7/1 — — — 8 0 POSTER VIEWING I Tuesday 28 April 2015 i57

showed cardiomegaly, possible right atrial enlargement and medias- Conclusion: TIO, although rare and can be challenging to diagnose, tinal lymphadenopathy. ECG showed prominent P waves and right outcome is rewarding once treated. Appropriate investigations axis deviation. She was treated for heart failure with ramipril, bisoprolol including the use of correct imaging technique are crucial to achieve and frusemide with clinical improvement. Dilated cardiomyopathy was early diagnosis and optimal clinical outcome. diagnosed. There were no signs or symptoms of an active CTD; her Disclosure statement: The authors have declared no conflicts of most recent dsDNA, complements, ESR and CRP were normal. A CT interest. coronary angiogram showed normal coronary arteries and a dilated SVC suggestive of pulmonary hypertension. Cardiac MRI revealed global late gadolinium enhancement sparing the subendocardial layer. 022. FOOT AND ANKLE INSUFFICIENCY FRACTURES IN Endomyocardial biopsies showed focal myocyte disarray and fibrosis RHEUMATOID ARTHRITIS: A CASE SERIES with some vacuolation but no inflammation on H&E staining. EM Jeanette C. Trickey1 and Nick Barkham1 studies are awaited. No other cause of the dilated cardiomyopathy 1Rheumatology, New Cross Hospital, Wolverhampton, UK was found and some histological features were in keeping with it being secondary to long-term HCQ use which was stopped. Background: This case series describes three patients with RA who Conclusion: Cardiac complications of HCQ are due to prolonged HCQ all had a foot or ankle insufficiency fracture. Insufficiency fractures can use inducing an acquired lysosomal storage disease with accumula- be difficult to diagnose in patients with RA. Presentation of an acutely tion of toxic metabolic products. Typical features are right bundle painful swollen ankle joint may be wrongly presumed to be a flare of branch block on ECG, progressing to 3rd degree heart block, left their inflammatory disease. This may lead to a delay in diagnosis of ventricle dysfunction, global hypokinesis and biatrial enlargement on insufficiency fracture. ECG and biventricular concentric hypertrophy, biatrial dilatation and Methods: Three patients with RA were noted to have insufficiency reduced systolic function on cardiac MRI. Endomyocardial biopsy may fractures of the ankle or foot. The fractures were not seen on X-ray be normal or show granulovacuolar cell mutations with little or no imaging and only diagnosed on MRI. Some of the fractures were in inflammation. EM is diagnostic and may show myeloid bodies and locations atypical of osteoporotic fractures. In two cases the patient curvilinear inclusion bodies and are awaited. Our patient had clinical, went on to have a stress fracture of neck of femur. imaging and some histological features consistent with HCQ-induced Results: Two of the patients had osteoporosis but were on treatment, cardiac disease. and recent DXA did not show significantly low T scores. CS use, Disclosure statement: The authors have declared no conflicts of particularly in high doses is a strong predictor of insufficiency fractures interest. independent of BMD. However these patients had not received multiple prescriptions of CS. Chronic inflammation, peri-articular osteopaenia and bony deformities are characteristic of RA. These patients all had active RA and were on biologic therapy. Two of the 021. A RARE CASE OF TUMOUR INDUCED OSTEOMALACIA patient had hindfoot deformities which may have biomechanically IN RHEUMATOLOGY contributed to the foot and ankle fractures. MTX in high doses for Elaine Y. Tang1 and Evin Sowden1 chemotherapy treatment of malignancies in children may cause bone 1Rheumatology, Pennine Acute Hospitals NHS Trust, Manchester, pain, osteoporosis and fractures. There have been some studies UK suggesting that MTX in low doses used for inflammatory arthritis can induce osteopathy. The first case report of two such patients had iliac Background: Tumour induced osteomalacia (TIO) is a rare acquired crest biopsies which showed osteoblast inhibition, thought to be the disorder of isolated renal phosphate wasting associated with mechanism by which MTX induces osteopathy. However one group phosphatonin-releasing tumour. Tumours are often small and of has found no effects of MTX in vitro or in vivo in low doses in mesenchymal origin. Evidence suggests that fibroblast growth participants with RA. There are reports of resolution of symptoms and factor-23 (FGF23) mediates TIO by inhibiting phosphate transport in X-ray changes after withdrawing MTX. However, the majority of these studies are small 2–3 patient case reports. In some instances no renal epithelial cells and impairing hydroxylation of 25(OH)D3. TIO symptoms usually precede identification of the responsible tumour. mention of BMD measurement in made. The majority of patients have Recommended investigation is by scintigraphy using octreotide been of varying doses of glucocorticoids in the past and bone biopsy labelling or combined with PET-CT. Definitive treatment is by resection was performed in only few cases. of tumour. Conclusion: These fractures were likely multifactorial in pathophysiol- Methods: We present the case of a 41 year old teaching assistant who ogy, but MTX osteopathy could be considered. It is important to presented to our District General Rheumatology Service in February suspect insufficiency fractures in patients with RA, even if initial X-ray 2012 with a 7 month history of scapular and right-sided neck pain. imaging appears normal. Also, have high index of suspicion of further Results: She was active and took part in regular exercise. She had fracture in patients with a history of stress fractures. cerebrovascular stroke at age 11 and epilepsy between ages 11 and Disclosure statement: The authors have declared no conflicts of 20 years. Investigations included normal bone profile and inflammatory interest. markers as well as chest, cervical, lumbar and SI joint X-rays. Apart from early cervical osteophytosis findings, radiological tests were 023. X-LINKED HYPOPHOSPHATAEMIA WITH MULTIPLE normal. She was commenced on amitriptyline, referred to physiother- SKELETAL MANIFESTATIONS apy and discharged to community care. She was re-referred to the Rheumatology Service in May 2013. Her pain was now radiating to Laura Watts1 and Paul Wordsworth1 lower back, groin and legs. She had difficulty in getting up, walking and 1Nuffield Department of Orthopaedics, Rheumatology and dressing. She reported no family history of joint or metabolic disorder. Musculoskeletal Sciences, Botnar Research Centre, Oxford, UK Clinical examination revealed proximal weakness in lower limbs without muscular tenderness with otherwise normal neurological Background: X-linked hypophosphataemia (XLH) is a rare genetic examination. Blood tests revealed elevated alkaline phosphatase condition caused by mutations in the PHEX gene, resulting in elevated (244 IU/l) but normal bilirubin and alanine transferase. Serum para- fibroblast growth factor-23, phosphaturia, hypophosphataemia and thyroid hormone level was raised (132 ng/l) with normal calcium level. skeletal abnormalities. Clinical manifestations include short stature, She was vitamin D sufficient (25 mg/l) and had a normal creatinine dental abscesses, bowing of the lower limbs and ossification of kinase level. Subsequent tests were arranged to support the tendons, ligaments and joint capsules. Here we describe the late suspected diagnosis of hypophosphataemic osteomalacia. Serum presentation of a severe case (aged 36) with a large number of phosphate level was low (0.58 mmol/l). 24-h urine calcium was complications. In particular, we present only the second reported case reduced (1.9 mmol/24 h) whereas 24-h urine phosphate was inappro- of syringomyelia associated with XLH and add to the literature on priately within normal range. An octreotide scan was requested. The spinal cord compression, hip impingement requiring hip replacement scan showed focal intense uptake at the medial aspect to the left distal and Chiari malformations that appear associated with this condition. femur which became more intense on the 24-h imagery. On SPECT-CT Methods: We report a case of a 36 year old man with late presentation this focal uptake localized to a nodule within soft tissues medial to the and diagnosis of XLH, and a review of case notes and radiographs of vastus medialis muscle measured 10 11 mm. She was referred to 60 patients with XLH under review in our clinic. endocrinologist with special interest in metabolic bone disease. Results: Our case presented extremely late (aged 36). The diagnosis Baseline serum FGF23 was found to be raised at 280 (0–99) ng/l. was only suspected when his daughter (aged 5) was referred for Initial phosphate and calcitriol supplementation produced partial investigation of short stature. It was noted coincidentally that he also clinical improvement. The detected lesion was removed surgically had short stature together with radiological evidence of enthesopathic and medical therapy stopped after surgery. The symptoms were fully change throughout his spine and ossification of the joint capsule and resolved with FGF23 level normalizing to 35 ng/l two months after trochanters around the hip. Biochemically, blood phosphate levels surgery. were low with an elevated ALP. Genetic testing revealed a C2066T i58 Tuesday 28 April 2015 POSTER VIEWING I

mutation in exon 20 of PHEX. Aged 23, he had undergone foramen 025. IMMUNOGLOBULIN G4 RELATED DISEASE: TWO magnum decompression for Chiari malformation and been noted to CASES SHOWING RESPONSIVENESS TO CORTICOSTEROIDS have syringomyelia throughout much of his spinal cord. This was ALONE associated with decreased sensation, weakness, wasting and trophic Kevin Yip1, Anoushka C. Seneviratne1 and Sundeept Bhalara1 changes of both hands. Prior to diagnosis he had undergone 1 intramedullary nailing of the right femur for deformity of the right leg Rheumatology, Watford General Hospital, Watford, UK causing intoeing gait, L2–5 laminectomy for spinal canal stenosis and multiple dental operations for dental abnormalities, which are Background: Immunoglobulin G4-related disease (IgG4-RD) is a commonly associated with this condition. He was subsequently recently recognized spectrum of fibroinflammatory diseases, linking noted to have a pseudofracture in the intertrochanteric region of the previously unrelated clinical diseases such as type 1 autoimmune right hip and a left renal stone. Aged 39, he underwent successful hip pancreatitis, Reidel’s thyroiditis, retroperitoneal fibrosis and Mikulicz replacement for impingement symptoms around his right hip from disease. IgG4-RD has been reported in almost 40 different organs, and primarily affects men aged over 50 years. Diagnosis relies on bony overgrowth. Later that year he developed sensory ataxia, a þ sensory level at the umbilicus, lower limb numbness and lower limb characteristic histopathological features of IgG4 plasma cell infil- hyperreflexia due to T9/10 spinal cord compression by calcified trates, obliterative phlebitis and a storiform pattern of fibrosis. Other ligamenta flava, which was successfully treated by surgical associated findings include tissue eosinophilia, an increased ratio of decompression. IgG4 to IgG plasma cells and elevated levels of serum IgG4 in 60–70%. Conclusion: XLH is a rare important diagnosis with manifestations Evidence suggests it is an autoimmune mediated disorder, but which can mimic other conditions, such as ankylosing spondylitis. We pathophysiology is not yet well defined. IgG4 antibodies are thought describe syringomyelia, Chiari malformation, spinal cord compression, to arise from a down-regulatory reaction to the disease process, rather pseudofracture, a renal stone and hip impingement requiring hip than being pathogenic. A Th2 response and activation of T regulatory replacement as complications of this condition. In our group of 60 cells results in increased IgE and IgG4 serum concentrations, patients under regular review we are aware of at least another 3 with eosinophilia and fibroblast production. Infiltration of inflammatory syringomyelia, 2 with Chiari malformations and 4 who have undergone cells, results in tumefactive masses, organ damage and fibrosis. No hip replacements. Severe skeletal deformity, fractures, arthritis and autoantigen has been identified, but an association with lactoferrin, enthesopathy are common complications often requiring multiple and carbonic anhydrase exists. Helicobacter Pylori has been proposed orthopaedic interventions. as a target for molecular mimicry. IgG4-RD responds well to Disclosure statement: The authors have declared no conflicts of glucocorticoids, but often steroid sparing agents such as AZA, MTX interest. and MMF have been used. B cell depletion with rituximab has proved effective in refractory cases. Methods: We describe two cases of IgG4-RD: a 75 year old man with 024. SUCCESSFUL MANAGEMENT OF A CASE OF a year’s history of progressive breathless and reduced exercise RELAPSING AND REFRACTORY CATASTROPHIC ANTI- tolerance; and an 85 year old woman with an 18 month history of a dry PHOSPHOLIPID ANTIBODY SYNDROME WITH ECULIZUMAB, cough, submandibular and cervical lymphadenopathy. A COMPLEMENT 5A INHIBITOR Results: Our male patient’s chest CT showed multiple spiculated lesions, with uptake on PET. Biopsy of these lesions confirmed IgG4þ Surabhi Wig1, Marian Chan2, Ian Bruce1 and Theresa Barnes2 plasma cells. His serum IgG4 level was elevated at 3g/l, his ESR was 1Rheumatology, Central Manchester University Hospitals Foundation 45 mm/h and CRP of 10.22 mg/l. He was treated with 50 mg of oral Trust, Manchester and 2Rheumatology, Countess of Chester Hospital prednisolone, tapered successfully over 6 months, with no recurrence NHS Foundation Trust, Chester, UK of his symptoms. A follow-up CT scan showed a reduction in size of some lesions and resolution of others. His serum IgG4 level fell to Background: Catastrophic antiphospholipid syndrome (CAPS) is the 1.1 g/l with treatment and his ESR normalized. Our female patient most severe and rare form of APS presenting with acute multiple organ underwent a lymph node biopsy, and histology demonstrated involvement, small vessel thrombosis and visceral damage. This is increased IgG4 plasma cells. Her serum IgG4 level was 5.5 g/l, her treated with anticoagulation, immunosuppression and plasmapher- CRP was 12.9 mg/l. She was successfully treated with a reducing esis. We present a case of CAPS which was refractory to conventional course of 40 mg of oral prednisolone over 6 months, with a reduction in therapy. size of her lymphadenopathy observed on interval CT scanning. Methods: Our patient, a 43 year old woman, was diagnosed with APS Conclusion: Immunoglobulin G4 related disease has a broad following an episode of axillary vein thrombosis, pregnancy morbidity, spectrum and a high index of suspicion should be held. These two presence of anti-cardiolipin antibodies and was commenced on cases add to the current body of evidence and illustrate that lifelong warfarin. Over the years she presented with acute hepatitic glucocorticoids alone can lead to an adequate treatment response. illness, acute renal failure, vasculitic lesions on extremities and Disclosure statement: The authors have declared no conflicts of polyarthralgias which were treated with steroids and AZA and then interest. MMF. CAPS was diagnosed when she presented with hypertensive crisis, thrombocytopenia, microangiopathic haemolytic anaemia, proteinuria and a renal biopsy revealed microthrombi. LN, haemolytic uremic syndrome and thrombotic thrombocytopenic purpura were 026. CASE SERIES: CLINICAL MANIFESTATIONS OF IGG4 excluded through renal biopsy, genetic testing and normal ADAMTS13 RELATED SYSTEMIC AUTOIMMUNE DISEASE levels, respectively. Despite adequate anticoagulation, i.v. steroids, CYC, rituximab and plasmapheresis, she developed further thrombotic Samy Zakout1, Patrick O’Beirn1 and Harsha Gunawardena1 and haemorrhagic episodes presenting as ocular, cerebellar and 1Rheumatology, Southmead Hospital, Bristol, UK pituitary infarctions and haemorrhages. We treated her with eculizu- mab, a mAb against complement C5 that blocks activation of terminal Background: Immunoglobulin G4-related disease (IgG4-RD) is an complement. increasingly recognized immune-mediated entity characterized by Results: Following this treatment, her platelets have improved from specific clinical, serological and histopathological features. The 31 109/l to 136 109/l. The estimated glomerular filtration rate has disease was first described in autoimmune pancreatitis and subse- improved from 7.3 ml/min to 17.4 ml/min and she has avoided dialysis. quent reports have highlighted other affected target organs (as She remains clinically well with no evidence of active disease. She has mentioned in the results section). Lesions demonstrate sclerosis with reduced her steroids to 10 mg every other day (pituitary infarct dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells prevents further reductions) and she lives a full and independent life generally associated with raised serum IgG4 concentrations. having made a significant improvement following her strokes. Methods: To report a retrospective analysis of patients diagnosed Conclusion: Eculizumab should be considered for treating relapsing with IgG4-RD who were seen in the North Bristol CTD and vasculitis and refractory cases of CAPS when the available first-line therapies clinic since 2013. The diagnosis was made based on clinical features fail. and supported by serum IgG4 levels, imaging studies and where Disclosure statement: The authors have declared no conflicts of appropriate tissue biopsy. We describe epidemiological characteris- interest. tics, clinical manifestations and immunomodulatory treatment. POSTER VIEWING I Tuesday 28 April 2015 i59

Results: Eleven patients were included in this analysis. The mean (S.D.) increasing comorbidity number and DAS28, HAQ and level of fatigue. age was 55.6 (20.4) years. Six patients (55.5%) were males. Ten (91%) Using the weighted comorbidity score did not increase correlation were Caucasian and one (9%) was Middle Eastern. IgG4 concentra- strength. Having two or more comorbidities was significantly asso- tions were elevated in 10 patients (91%). The patient with normal IgG4 ciated with increased odds of having high baseline HAQ, which levels at presentation to clinic had IgG4 checked after the referring remained significant even after adjusting for age, gender and baseline team had commenced steroid treatment. The mean (S.D.) IgG4 DAS28 [odds ratio 1.38 (95% CI 1.08, 1.80)]. concentration was 3.73 (3.75) g/l (normal <1.32 g/l). All patients were Conclusion: Use of patient-reported comorbidity questionnaires are ANA negative and 3 (27%) were ANCA positive (atypical staining valid methods of quantifying comorbidity in clinical rheumatological pattern and PR3/ and MPO negative). Complement levels (C4) were settings. The association between comorbidity and disability, even after low in one patient (9%) and CRP was raised in 3 patients (27%). adjusting for disease activity, suggests that comorbidity is an important Patients had clinical features secondary to the following organs involved either individually or in combination: thyroid enlargement, 027 TABLE 1. Baseline variables and association with a high HAQ score (>1) dacryoadenitis, sinus disease, salivary gland enlargement, orbital pseudotumour, lungs (follicular bronchiolitis and parenchymal infiltra- Variable Univariate association with a tion), biliary disease, tubulointerstitial nephritis, autoimmune pancrea- high HAQ (>1) titis, retroperitoneal fibrosis, aortitis/large vessel vasculitis or prostate. Five patients underwent biopsies (lacrimal gland, salivary gland, lung, Value Odds 95% CI retroperitoneal tissue or kidney). All biopsies demonstrated classic ratio IgG4 plasma cell tissue infiltration. All patients had imaging studies, Age, median (IQR), years 57.2 (16.2) 1.00 0.98, 1.02 which included ultrasound in some, CT and MRI (standard scans plus Female, n (%) 144 (63.4) 1.02 0.59, 1.76 DAS28, median (IQR) 5.1 (1.31) 1.95 1.52, 2.49 angiographic sequences where appropriate) that showed character- HAQ, median (IQR) 0.875 [0.5, 1.375] — — istic lesions, and PET-CT scans in 2 patients with retroperitoneal Fatigue VAS, median (IQR) 65 [40, 95] 1.00 1.00, 1.00 fibrosis and aortitis. All patients responded clinically and radiologically Number of comorbidities, 1 [0, 2] 1.39 1.17, 1.67 to prednisolone, with either maintenance MTX or AZA. median (IQR) Conclusion: Our retrospective case study provides data on this No comorbidity, n (%) 64 (28.2) 1 (ref) — important differential diagnosis in patients who present with organ 1 Comorbidity, n (%) 67 (29.5) 1.39 0.67, 2.75 specific or systemic inflammatory disease to a variety of clinical 2 Comorbidities, n (%) 42 (18.5) 2.90 1.29, 6.48 3 Comorbidities, n (%) 54 (23.8) 3.28 1.54, 7.00 specialities including rheumatology. We appreciate that patients were Weighted comorbidity score, 2 (0–5) 1.16 1.07, 1.27 seen in a tertiary CTD vasculitis clinic, however importantly this median (IQR) highlights the broad spectrum of manifestations seen in IgG4-RD. Retroperitoneal fibrosis and/or aortitis were prevalent clinical features DAS28: DAS for 28 joints; IQR: interquartile range; VAS: visual analogue scale. in our cohort. All patients responded well to conventional immuno- confounder when assessing disability outcome in eRA. Comorbidity modulatory treatment. In summary, IgG4-RD is an important immune- should be a core data item collected in observational studies. mediated syndrome that remains poorly understood. Awareness and Disclosure statement: The authors have declared no conflicts of early recognition is key to prevent progressive organ disease, where interest. CS and other immunomodulatory therapy are effective. Disclosure statement: The authors have declared no conflicts of interest. 028. RISK OF PNEUMOCYSTIS JIROVECII PNEUMONIA IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH ANTI-TUMOUR NECROSIS FACTOR THERAPY: RESULTS FROM THE BSRBR-RA EPIDEMIOLOGY Ellen S. Bruce1, Lianne Kearsley-Fleet1, Kath D. Watson1, Deborah P. Symmons1 and Kimme L. Hyrich1 1Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, 027. SELF-REPORTED COMORBIDITY BURDEN Manchester Academic Health Science Centre, University of CORRELATES WITH FUNCTIONAL DISABILITY AND DISEASE Manchester, Manchester, UK ACTIVITY IN EARLY RHEUMATOID ARTHRITIS Background: Certain opportunistic infections are becomingly increas- Aleena Abdullah1, Christopher Sparks1, Steven Zhao1, ingly recognized in patients with RA treated with anti-TNF therapy. Cristina Estrach2 and Nicola J. Goodson1 Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection 1Rheumatology, University of Liverpool and 2Rheumatology, known to be associated with T cell abnormalities, most commonly that University Hospital Aintree, Liverpool, UK of HIV has been reported in patients with RA on anti-TNF therapy. This analysis aimed to determine whether anti-TNF therapy is associated Background: Comorbid disease may influence disability outcomes in with an increase in risk of PJP in patients with RA compared with non- RA. However, accurately measuring comorbid disease burden is biologic DMARD (nbDMARD). complex and time consuming. Use of patient-reported comorbidity Methods: Using data from the British Society for Rheumatology questionnaires may be a useful method to quantify comorbidity in the Biologics Register for RA (BSRBR-RA), a national prospective clinical setting and in observational studies in rheumatology. The aim observational cohort study, the risk of PJP was compared between of this study was to explore whether self-reported comorbidity burden 13 905 anti-TNF treated and 3677 nbDMARD treated patients. Patients correlates with disease activity and functional disability at presentation were followed up by 6-monthly clinical and patient questionnaires for with early RA (eRA). the initial 3 years and clinical questionnaires yearly thereafter. All Methods: At time of eRA diagnosis, patients attending Aintree Early possible cases of PJP reported to the BSRBR-RA were identified and Arthritis clinic, completed a modified, validated, patient-reported 14 item validated. Cases were validated as definite events when microbiolo- comorbidity questionnaire. Each comorbid condition scores 1 point gical or PCR confirmation of infection was identified or in the presence (maximum score 14). Comorbidity treatment or associated impairment of post mortem or death certificate evidence. The primary analysis was contributes to a weighted comorbidity score (maximum score 42). The an on-drug analysis with anti-TNF subjects contributing time at risk number of comorbid conditions were divided into four categories: no from the start of treatment and censored at PJP event, 90 days after comorbidity (reference); low 1; medium ¼ 2; and high 3. Correlation the last dose, date of last received follow-up form or death, whichever between comorbidity number and weighted score and the DAS for 28 came first. Baseline characteristics were compared between anti-TNF joints (DAS28) and modified HAQ were assessed. Logistic regression and nbDMARD cohorts using non-parametric descriptive statistics. was used to identify associations between comorbidity category and Crude incident rates were calculated for each cohort and the relative high DAS28 (>5.1) and high HAQ (>1) at baseline. risk between the two cohorts was calculated using Cox proportional Results: 227 patients had complete comorbidity, HAQ, DAS28 and hazards regression model. fatigue visual analogue scale data at baseline (Table 1). 71.8% of the Results: 28 possible PJP cases were reported to the BSRBR-RA, 13 cohort reported comorbidity. The most frequently reported comorbid- cases were validated as definite infections (11 anti-TNF, 2 nbDMARD). ities were back pain (35.53%), hypertension (28.07%) and OA Incident rates were: anti-TNF 1.4 per 10 000 person-years (pyrs) follow (21.93%). Linear regression revealed strong correlation between up (95% CI 0.67, 2.50), nbDMARD 1.0 per 10 000 pyrs follow up (95% CI i60 Tuesday 28 April 2015 POSTER VIEWING I

0.12, 3.80). The hazard ratio (adjusted for age) of PJP in the anti-TNF on- 2.74), with higher values showed for male gender (SIR 3.10, 95% CI drug analysis was 1.68 (95% CI 0.36, 7.84). There was no difference in 1.55, 4.65) than female gender (SIR 1.95, 95% CI 1.31, 2.61). 7/13 mean age of patients at the time of PJP infection or baseline CS use were adenocarcinoma, mainly breast, 4/13 squamous cell and the between the two treatment groups. The mean time to PJP infection was remainder haematological malignancy. 7.02 months (S.D. 6.23) after anti-TNF commencement. Conclusion: The association of malignancy with PM/Scl reactivity in Conclusion: Pneumocystis pneumonia is a rare infection with only a SSc is of interest in the context of recent studies describing a potential small number of cases identified in the study. Therefore, the results pathogenic role of anti-RNA polymerase III antibodies with malignant obtained do not allow for any definitive conclusions to be made disease in SSc. This cohort is otherwise representative of others in regarding the risk of PJP in RA patients treated with anti-TNF therapy. terms of demographics and clinical characteristics and underlines the The data suggest this infection is occurring early in the treatment with importance of close surveillance for concurrent malignancy in all SSc anti-TNF therapy. disease subphenotypes. Disclosure statement: The authors have declared no conflicts of Disclosure statement: The authors have declared no conflicts of interest. interest.

029. ASSOCIATION OF ANTI-PM/SCL ANTIBODY WITH RISK 030. IMPACT OF SMALL SPINAL CURVES IN ADOLESCENTS OF MALIGNANCY IN SCLERODERMA THAT HAVE NOT PRESENTED TO SECONDARY CARE Cosimo Bruni1, Ana Lages2, Hitesh Patel3, Jennifer Harvey3, Emma M. Clark1, Hilary Taylor1, John Hutchinson2, Ian Nelson2, Voon Ong4, Marco Matucci-Cerinic1, Emma Derrett-Smith4 and Becki Wordsworth1, Ian Harding2 and Jon Tobias1 Christopher P. Denton4 1Musculoskeletal Research Unit, University of Bristol and 2Spinal 1Experimental and Clinical Medicine, Section of Rheumatology, Surgery Unit, North Bristol NHS Trust, Bristol, UK Azienda Ospedaliera Universitaria Careggi, Firenze, Italy, 2Affiliation servicio de Medicina Interna, Hospital De Braga, Braga, Portugal, Background: Adolescent idiopathic scoliosis is present in 3–5% of the 3Department of Clinical Immunology, Royal Free Hospital and general population. Large curves are associated with increased pain 4Centre for Rheumatology and Connective Tissue Diseases, and reduced quality of life. However, no information is available on the University College London Medical School, Royal Free Campus, impact of smaller curves, many of which do not reach secondary care. London, UK The objective of this project was to identify whether or not there is any hidden burden of disease associated with smaller spinal curves. Background: Anti-PM/Scl antibodies are heterogeneous autoantibo- Methods: The Avon Longitudinal Study of Parents and Children dies in scleroderma (SSc) directed mainly against 75 kDa and 100 kDa (ALSPAC) is a population-based birth cohort that recruited over 14 000 human exosome components, associated with overlap syndromes. pregnant women from the Bristol area between 1991 and 1992 and Published data suggest that up to 12.5% of SSc patients carry this has followed up their offspring regularly. At aged 15 presence or seropositivity with associations with myositis, mild skin involvement, absence of spinal curvature 6 degrees was identified using the pulmonary fibrosis, articular involvement and calcinosis and a lower validated DXA scoliosis measure in 5299 participants. At age 18, a prevalence of pulmonary arterial hypertension (PAH) and gastrointest- structured pain questionnaire was administered to 4083 participants. inal involvement. In this study, we characterized the clinical and Chi-squared was used to investigate any association between detailed serological phenotype of anti-PM/Scl positive SSc patients presence of a spinal curve at aged 15 and self-reported pain at age from a single-centre cohort of 2200 patients and identified a cohort 18 years. Sensitivity analyses were performed by rerunning analyses within this group with increased risk of malignancy. after excluding those who were told at aged 13 they had a spinal curve Methods: Anti-PM/Scl positive SSc patients identified by indirect (n ¼ 27), and using a higher spinal curve cut-off of 10 degrees. immunofluorescence pattern and confirmed on counter-immunoelectro- Results: Full data was available for 3184 participants. Of these, 56.8% phoresis were enrolled in the study. Demographics and clinical data on were female, and 4.2% non-white, reflecting the local population. 202 skin, internal organ involvement and history of malignancy were recorded. (6.3%) had a spinal curve 6degrees and 125 (3.9%) had a curve 10 Results: 70 anti-PM/Scl positive patients were identified (3.1% of degrees. The mean curve size was 12 degrees. 140/202 (69.3%) had cohort), with frequent lung (57.1%), gastrointestinal (62.9%) and single curves, and 57.4% of these were to the right. In total 46.3% of muscle involvement (61.4%) as described previously (Table 1). 48 the 3184 participants reported aches and pains that lasted for a day or patients (68.6%) had antibodies targeting both PM/Scl 75 and 100; 6 longer in the previous month, consistent with previous literature. (8.6%) PM/Scl 75 only and 16 (22.8%) PM/Scl 100 antibody only. 16.3% reported back pain. Those with spinal curves 6 degrees were There was a significant association between positivity for anti-PM/Scl 42% more likely to report back pain than those without (odds ratio 100 alone and malignancy (P ¼ 0.037) when compared with presence 1.42, 95% CI 1.00, 2.02, P ¼ 0.047). In addition, those with spinal of both reactivities or reactivity to PM/Scl75 alone. 13 patients (18.6%) curves had more days off school, were more likely to avoid activities had developed a malignancy, 4 (30.7%) of these had onset within 36 that caused their pain, were more likely to think that something harmful months from SSc diagnosis and all were positive for anti-PM/Scl 100, is happening when they get the pain, and were more afraid of the pain combined with anti-PM/Scl75 in 7/13 (53.8%). The study population than people without spinal curves (P < 0.05). Sensitivity analyses did standardized incidence ratio (SIR) for cancer was 2.14 (95% CI 1.55, not change results. Conclusion: We present the first results from a population-based study of the impact of small spinal curves and identify an important hidden burden of disease. Our results highlight that small scoliotic curves that may not present to secondary care are nonetheless associated with increased pain, more days off school and avoidance 029 TABLE 1. Prevalence of clinical, instrumental and laboratory features in the of activities. study population Disclosure statement: The authors have declared no conflicts of Total PM-Scl PM-Scl Cancer vs interest. population patients non-cancer (n ¼ 70, 100%) with cancer population (n ¼ 13, 18.6%) P-value 031. THIS ABSTRACT HAS BEEN MOVED TO THE ORAL ABSTRACTS SECTION Age, median (S.D.), years 58.4 (14.0) 60.9 (10.3) 0.566 Female, % 80.0 69.2 0.277 Age at SSc onset, 44.1 (14.5) 46.5 (9.9) 0.365 median (S.D.), years Age at cancer onset, 55.2 (11.7) NA mean (S.D.), years Smoking history, % 45.7 53.8 0.486 LcSSc 67.1 76.9 0.740 DcSSc 28.6 23.1 mRSS, median 4 11 0.204 Digital ulcers, % 20.0 38.5 0.119 Calcinosis, % 38.6 38.5 >0.99 Gastrointestinal involvement, % 62.9 69.2 0.756 Pulmonary hypertension, % 10.0 15.4 0.611 Myositis overlap, % 61.4 53.8 0.545 Lung involvement, % 57.1 53.8 >0.99 Articular involvement, % 38.6 15.4 0.067 Renal involvement, % 5.7 7.7 0.569 POSTER VIEWING I Tuesday 28 April 2015 i61

032. INCIDENCE AND MORTALITY OF RELAPSING Results: The mean (S.D.) age of study participants was 75.7 (2.6) years. POLYCHONDRITIS IN THE UNITED KINGDOM: A Low PP, according to our definition, was present in 116 (56.9%) men POPULATION-BASED COHORT STUDY and 141 (71.2%) women. Radiographic hip or knee OA was common, and present in 43.5% and 54% for hip and knee respectively. Clinical Nisha Hazra1, Alexandru Dregan1, Judith Charlton1, Martin Gulliford1 2 OA was less prevalent; 17.8% participants had either a clinical and David D’Cruz definition of hip or knee OA, and 2.5% participants had a clinical 1Division of Primary Care and Public Health Research, King’s College 2 diagnosis of OA at both sites. In this population, a radiographic London and Louise Coote Lupus Unit, Guy’s and St Thomas’ diagnosis of OA at neither the hip (RR 0.95, 95% CI 0.81, 1.12) nor the Hospital, London, UK knee (RR 1.05, 95% CI 0.90, 1.23) was significantly associated with low PP, before or after adjustment for confounders. By contrast, a Background: Relapsing polychondritis is a rare disease characterized clinical diagnosis of OA was significantly associated with poor PP, with by inflammation of cartilage. Our aim was to estimate the incidence, relationships strongest for those individuals with a clinical diagnosis at prevalence and mortality of relapsing polychondritis and to describe both sites (RR 1.44, 95% CI 1.14, 1.82, P ¼ 0.002, after adjustment for the clinical features of relapsing polychondritis in a large population. age, sex, education, alcohol and BMI). Methods: All participants diagnosed with relapsing polychondritis Conclusion: Radiographic OA is common in older individuals, but is were sampled from the Clinical Practice Research Datalink (CPRD). less strongly associated with PP than a clinical definition of OA. Prevalence and incidence rates for 1990–2012 were estimated. Disclosure statement: The authors have declared no conflicts of Relative mortality of relapsing polychondritis cases was estimated in interest. a time-to-event framework using UK life tables for reference. A questionnaire validation study was performed to assess diagnostic accuracy. 034. ANXIETY AND DEPRESSION ARE ASSOCIATED WITH Results: There were 117 participants with relapsing polychondritis NON-ADHERENCE TO METHOTREXATE IN THE FIRST 6 ever recorded. In the validation study, 50/61 (82%) of cases were MONTHS OF TREATMENT IN A RHEUMATOID ARTHRITIS confirmed by a physician and unconfirmed cases were excluded. The POPULATION analysis included 106 participants (42 men, 64 women) diagnosed with Holly F. Hope1, James Anderson1, Anne Barton1, Lis Cordingley2, relapsing polychondritis. The mean age (range) at diagnosis in men Kimme Hyrich3 and Suzanne M. M. Verstappen3 was 55 (17–81) years and in women 51 (11–79) years. The median 1NIHR Manchester Musculoskeletal Biomedical Research Unit, interval from first symptom consultation to diagnosis was 1.9 years. University of Manchester, 2Centre for Musculoskeletal Research, The incidence of relapsing polychondritis between 1990 and 2012 was University of Manchester and 3Arthritis Research UK Centre for 0.71 (0.55–0.91) per million population per year. There were 19 deaths Epidemiology, University of Manchester, Manchester, UK from any cause. There were 16 observed deaths eligible for survival analysis and 7.4 deaths expected for the UK population of the same Background: MTX is the first-line treatment for RA in the UK, however age, sex and period. The standardized mortality ratio was 2.16 (1.24– response is not universal and non-adherence may partially explain poor < 3.51), P 0.01. Respiratory disease, cardiac conditions and cancer response. Previous estimates of adherence have not differentiated were the most frequent causes of death. between periods of non-adherence and those in which patients adhere Conclusion: The incidence of relapsing polychondritis may be lower to medical advice to miss a dose of MTX. This study aimed to conduct than previously estimated and diagnostic misclassification and delay an in-depth descriptive analysis of adherence to MTX during the first may be frequent. Mortality in relapsing polychondritis is more than 6 months and to identify potential predictors of non-adherence. twice that of the general population. Methods: Patients were recruited to the Rheumatoid Arthritis Disclosure statement: The authors have declared no conflicts of Medication Study (RAMS), a multicentre prospective cohort of incident interest. MTX users with a diagnosis of RA or inflammatory polyarthritis in the UK. At baseline, clinical history, DAS for 28 joints, disease duration, HAQ, visual analogue scales (VAS) general well-being, pain & fatigue, demographic, alcohol and smoking data were collected. In addition, 033. RADIOGRAPHIC OSTEOARTHRITIS IS LESS STRONGLY patients completed The Beliefs about Medicines Questionnaire (BMQ), ASSOCIATED WITH PHYSICAL PERFORMANCE THAN Brief Illness Perceptions Questionnaire (BIPQ), Hospital Anxiety and CLINICAL OSTEOARTHRITIS IN OLDER INDIVIDUALS Depression Scale (HADS), and the EQ-5D. To measure adherence Elaine Dennison1, Mark Edwards1, Camille Parsons2, Anna during the first 6 months after MTX commencement patients E. Litwic1, Cyrus Cooper1 and Avan Aihie Sayer3 completed a weekly MTX diary reporting any missed doses and 1Rheumatology, MRC Lifecourse Epidemiology Unit, University reasons. Adherence was calculated as the proportion of weeks Hospital Southampton, 2MRC Lifecourse Epidemiology Unit, MRC patients took MTX as directed by their consultant, including weeks Lifecourse Epidemiology Unit, University Hospital Southampton and when MTX wasn’t taken following medical advice. Nonadherence was defined as 1 dose missed against medical advice. Univariate 3Elderly Care, MRC Lifecourse Epidemiology Unit, University regression analyses were applied to test the association between Hospital Southampton, Southampton, UK possible predictors and non-adherence. Results: 552 patients provided 13 253 weeks of diary data, 12 564 Background: Poor physical performance (PP) is associated with weeks (97.4%) were adherent. 142/552 (25%) patients reported 342 disability, lower quality of life and higher mortality rates. We have non-adherent weeks (2.6%), 110/552 (20%) patients reported 347 previously demonstrated relationships between hip and knee OA adherent weeks (2.6%) where MTX was missed following medical according to the clinical ACR definition and PP, before and after advice. Reasons for non-adherence (%non-adherent weeks) included; adjustment for pain scores. Here we study associations between PP feeling unwell (63.2%), forgot (10.9%), drug holiday (10.4%), ran out and a radiographic definition of hip and knee OA. (8.4%), changed dose (7.3%). Higher tender joint count, fatigue, Methods: Data were available for 222 men and 221 women who depression & anxiety scores at baseline predicted non-adherence at 6 participated in the UK component of the European Project on months (Table 1). Osteoarthritis (EPOSA) and, who originally participated in the Conclusion: Initial adherence to MTX was higher than previously Hertfordshire Cohort Study (HCS), UK. Participants completed a nurse reported (59–88%), possibly because not all omitted MTX doses may administered questionnaire detailing self-reported OA. A clinical diag- have been attributable to non-adherence. Understanding the reasons nosis of OA was defined based on ACR criteria using history and that underpin non-adherence to MTX may facilitate the development of examination findings. Hip and knee radiographs were taken and graded targeted interventions to modify behaviour and improve adherence. for overall Kellgren–Lawrence score, with a positive definition reflecting a Disclosure statement: The authors have declared no conflicts of K & L score of 2 or above. PP was determined from assessments of interest. walking speed, chair stands and balance (tandem stand) to create a composition score (0–12); low PP was defined as 9. i62 Tuesday 28 April 2015 POSTER VIEWING I

034 TABLE 1. Baseline characteristics of patients and the respective association with non-adherence at 6 months 100% Adherenta 1 Non-adherent weeka Univariate effect size

Predictor n Statisticb n Statisticb n OR (95% CI) P Age, years 399 61.9 (50.1–69.9) 135 61.1 (51.0–70.1) 534 0.995 (0.980, 1.01) 0.547 Female, n (%) 404 271 (67.1) 139 105 (75.5) 543 1.516 (0.977, 2.35) 0.063 Symptom duration, months 400 9.5 (4.5–32.1) 136 11.9 (5.5–26.5) 536 0.993 (0.997, 1.00) 0.649 Current smoker, n (%) 400 72 (18.0) 138 23 (16.%) 538 0.911 (0.544, 1.53) 0.723 Currently drinks alcohol, n (%) 392 284 (72.5) 132 87 (65.9) 524 0.735 (0.482, 1.12) 0.154 DAS28 393 4.9 (2.3–7.0) 135 6 (3.2–7.8) 483 1.17 (0.988, 1.35) 0.071 Tender joint count (28) 332 6 (2–12) 132 9 (4–15) 500 1.03 (1.01, 1.06) 0.015* Swollen joint count (28) 368 6 (2–11) 132 6 (3–11) 500 1.01 (0.978, 1.04) 0.550 Patient VAS 368 4.4 (2.6–6.0) 132 4.0 (2.2–6.0) 540 1.05 (0.968, 1.14) 0.240 Physician VAS 387 3.5 (2.0–5.6) 133 3.7 (2.6–5.9) 520 1.08 (0.988, 1.17) 0.091 Pain VAS 395 4.8 (2.5–6.9) 135 5.6 (2.9–7.4) 530 1.07 (0.993, 1.15) 0.077 Fatigue VAS 393 4.9 (2.3–7.0) 135 6.0 (3.2–7.8) 528 1.10 (1.03, 1.18) 0.007** CRP 332 9.15 (5.00–23.0) 117 11.0 (5.00–25.6) 449 1.00 (0.997, 1.01) 0.280 HAQ 395 1.00 (0.500–1.63) 138 1.125 (0.500–1.75) 533 1.19 (0.915, 1.55) 0.193 EQ-5D 384 0.656 (0.516–0.760) 134 0.656 (0.516–0.727) 518 0.712 (0.369, 1.38) 0.313 BMQ-necessity 380 19.5 (17–22) 133 20 (17–23) 510 0.984 (0.932, 1.04) 0.570 BMQ-concern 380 15 (13–17) 133 15 (12–17) 513 1.01 (0.960, 1.07) 0.679 IPQ-consequences 394 6 (3–8) 136 6 (4–8) 530 1.07 (0.988, 1.16) 0.095 IPQ-timeline 385 10 (7–10) 128 10 (7–10) 513 1.01 (0.926, 1.01) 0.843 IPQ-personal control 393 6 (4–8) 136 6 (4–8) 529 1.01 (0.939, 1.09) 0.786 IPQ-treatment control 388 2 (1–3) 135 2 (1–3) 523 0.994 (0.885, 1.12) 0.925 IPQ-identity 393 7 (5–8) 137 7 (5–8) 530 1.07 (0.977, 1.16) 0.150 IPQ-illness concern 392 8 (6–10) 396 9 (7–10) 529 1.09 (0.9998, 1.19) 0.051 IPQ-coherence 396 2 (1–5) 135 2 (1–5) 531 0.997 (0.915, 1.09) 0.095 IPQ-emotional rep 396 6 (3–8) 135 7 (4–8) 531 1.06 (0.991, 1.13) 0.091 HADS Depression 391 7 (3–10) 136 7 (4–11) 527 1.05 (1.00, 1.10) 0.047* HADS Anxiety 391 8 (5–11) 136 10 (6–12) 527 1.06 (1.01, 1.11) 0.019* aData are median (IQR) or n (%); *P < 0.01. BMQ: Beliefs in Medicines Questionnaire; DAS28: DAS for 28 joints; HADS: Hospital Anxiety Depression Scale; HAQ: Health Activity Questionnaire; IPQ: Illness Perception Questionnaire; IQR: interquartile range; OR: odds ratio; VAS: Visual Analogue Scale.

035. COMPREHENSIBILITY OF GLOBAL MEASURES FOR France, Netherlands, Romania, Italy and Canada). Patients provided AT-WORK PRODUCTIVITY IN PATIENTS WITH RHEUMATIC baseline demographic, clinical and occupational characteristics, after CONDITIONS: AN INTERNATIONAL QUALITATIVE STUDY which a cognitive debriefing interview took place. Patients were 1 2 2 randomly allocated to be interviewed on 3/5 global measures [Work Sarah A. Leggett , Antje van der Zee-Neuen , Annelies Boonen , Productivity Scale-RA (WPS-RA), Work Productivity and Activity Dorcas Beaton3, Mihai Bojinca4, Ailsa Bosworth5, Sabrina Dadoun6, 6 7 8 9 Impairment Questionnaire (WPAI), Work Ability Index (WAI), Quality Bruno Fautrel , Sofia Hagel , Catherine Hofstetter , Diane Lacaille , and Quantity questionnaire (QQ), and WHO Health and Performance Denise Linton10, Carina Mihai4, Ingemar F. Petersson11, 9 12 1 Questionnaire (HPQ)], with the WPAI being asked for all patients as a Pam Rogers , Carlo Scire´ and Suzanne M. M. Verstappen standard measure of comparison between countries and patients. In 1Arthritis Research UK Centre for Epidemiology, University of 2 addition, all five measures were given to the patients with the Manchester, Manchester, UK, Department of Rheumatology, requirement of stating their most preferred measure. NVivo software Maastricht University Medical Centre, and Caphri Research Institute, was used to code the data into four themes: constructs, recall period, Maastricht, The Netherlands, 3Mobility Program Clinical Research 4 reference and attribution. Unit, St Michael’s Hospital, Toronto, ON, Canada, Internal Medicine Results: 57% of the study population was female; mean age was 45.6 and Rheumatology Clinic, Dr Ion Cantacuzino Hospital, Carol Davila 5 (S.D. 10.7) years and median symptom duration 13.5 (S.D. 10.07) years. University of Medicine and Pharmacy, Bucharest, Romania, Patient Discrepancies in the interpretation of constructs between countries Partner, National Rheumatoid Arthritis Society, Maidenhead, UK, were found for the HPQ, with Romania and Sweden interpreting 6Department of Rheumatology, Universite´ Pierre et Marie Curie, 7 performance to relate to sports rather than work (Table 1). Some Paris, France, Department of Clinical Sciences, Section for expressed difficulties in scoring their productivity (WPAI & WPS-RA) Rheumatology, Lund University and Skane University Hospital, Lund, 8 due to a lack of producing products in their job (e.g. nurse vs. factory Sweden, Patient Partner, Canadian Arthritis Patient Alliance, worker). 70% of patients said 7 days (WPAI) was an accurate Toronto, ON, Canada, 9Arthritis Research Centre of Canada, 10 representation of how their condition affects work productivity. 58% University of British Columbia, Vancouver, BC, Canada, Mobility reported the today time period (QQ) to be an inaccurate representation Program Clinical Research Unit, St Michael’s Hospital, Toronto, ON, as many patients had not yet attended work that day. The compared Canada, 11Orthopaedics, Clinical Sciences Lund University, Lund, 12 with normal reference in the QQ caused difficulty due to the Sweden and Epidemiology Unit, Italian Society for Rheumatology, ambiguous nature of the word normal, as did rating the performance Milan, Italy of colleagues (HPQ), with patients feeling uncomfortable judging the performance of co-workers. Overall, the WPAI was voted the most Background: There are a number of global measures available to relevant, making it the most favoured measure, while the WAI was the explore at-work productivity loss (presenteeism) in patients with least favoured. rheumatic conditions. However, large variations in results are seen Conclusion: From a patient perspective, it appears there is no perfect which might be partly attributed to differences in content across four measure for all individuals and cultures involved in this study. The lack aspects: constructs addressed, recall period used, disease attribution of consensus and difficulties expressed with the measures reinforces and reference. The purpose of this international qualitative study was the need for a universally accepted and language applicable measure. to identify, from a patient’s perspective, difficulties and differences in This would facilitate comparisons of presenteeism results across the interpretation of five global measures of presenteeism across studies and countries. seven countries in patients with inflammatory arthritis and OA. Disclosure statement: The authors have declared no conflicts of Methods: 70 patients with a diagnosis of inflammatory arthritis or OA interest. in paid employment were recruited from seven countries (UK, Sweden,

035 TABLE 1. Example interpretations of each global construct across countries WPAI & WPS-RA, productivity QQ, quality and quantity WAI, work ability HPQ, performance WPS-RA, interference Efficacy (UK) Accuracy (Sweden) Fulfil (Canada) Competing sports (Romania) Interrupt (Italy) Output (Romania) Amount (Netherlands) Performance (France) Effective (Canada) Impact (UK) Performance (Canada) 100% (UK) Able (Italy) Sports related (Sweden) Influence (Romania) QQ: Quality and Quantity questionnaire; WAI: Work Ability Index; WPAI: Work Productivity and Activity Impairment Questionnaire; WPS-RA Work Productivity Scale-RA. POSTER VIEWING I Tuesday 28 April 2015 i63

036. ASSESSMENT OF LOWER LIMB BONE STRENGTH BY For hand pain, a linear model was optimal and, after adjustment for DIFFERENT METHODS: OBSERVATIONS FROM THE factors associated only with the model intercept, progression of hand HERTFORDSHIRE COHORT STUDY pain i.e. the slope of the model, was predicted by: the SF-12 Physical 1 1 1 Component Score (P < 0.001), number of days with hand pain in the Anna E. Litwic , Michael Clynes , Karen A. Jameson , last 12 months (P ¼ 0.027), hand function (P < 0.001), pinch strength Hayley J. Denison2, Mark Edwards1, Cyrus Cooper1 and 1 (P < 0.001) and the number of joints with radiographic hand OA Elaine M. Dennison (P ¼ 0.001). Based on this model, the overall average rate of 1Rheumatology, MRC Lifecourse Epidemiology Unit, University 2 progression in AUSCAN Pain per year was 0.05 points. When a Hospital Southampton, Southampton, UK and School of Biological linear model was applied to hand function, the only predictor of Sciences, Victoria University of Wellington, Wellington, New Zealand progression common to both outcomes was physical function (P ¼ 0.001). Additional predictors in the hand function model were: Background: Hip fracture is the most significant complication of age (P ¼ 0.020), number of comorbidities (P < 0.010), hand pain osteoporosis in terms of mortality, long-term disability and decreased (P < 0.001) and the grip-ability test (P ¼ 0.001), which resulted in an quality of life. While BMD is a well-recognized strong predictor of overall average rate of progression of 0.08 AUSCAN Function points osteoporotic fracture, proximal femur geometry (PFG) parameters per year. have also been proposed to be predictive of mechanical strength and Conclusion: On average, the rate of long-term progression of femoral neck fracture risk. Here we report associations between hand pain and function is small over time. However variation exists femoral strength, using Hologic Hip Structural Analysis (HSA) of DXA between individuals that can be partly explained by a combination images, and an assessment of tibial bone strength, using peripheral of hand-specific and more general factors, including some that QCT (pQCT). may be interpreted as markers of musculoskeletal ageing and Methods: 488 men and 431 women from the Hertfordshire Cohort frailty. Further work is needed, however, to test whether such Study attended a study visit where they underwent bone densitometry factors are replicated in an external dataset and to explore whether using a Hologic QDR 4500 instrument. The structural geometry of the they can be developed to be accessible for use in practice and left hip was measured using the Hologic HSA programme for each research. DXA scan. Peripheral pQCT measurements of the tibia were obtained Disclosure statement: The authors have declared no conflicts of using a Stratec XCT 2000 instrument. Data were analysed using the interest. Stata statistical software package. Results: The mean age of participants was 64.8 (S.D. 2.5) years in men and 66.3 (S.D. 2.6) years in women. There were strongly 038. HOW WELL DO RADIOGRAPHIC, CLINICAL AND significant sex differences in most femoral geometry parameters SELF-REPORTED DIAGNOSES OF KNEE OSTEOARTHRITIS measured (P < 0.001), except narrow neck buckling ratio (P ¼ 0.02) AGREE? FINDINGS FROM THE HERTFORDSHIRE COHORT and shaft neck angle (P ¼ 0.03) There were significant (P < 0.001) STUDY associations between pQCT derived measures of tibial width, Camille Parsons1, Michael Clynes1, Holly Syddall1, endocortical diameter and cortical thickness with the corresponding 1 1 2 HSA variable. In particular, we observed strong relationships Darshan Jagannath , Anna Litwic , Suzan van der Pas , Cyrus Cooper1 and Mark H. Edwards1 between tibial polar strength strain index at the 38% slice with 1 ¼ ¼ Medical Research Unit LEU, University of Southampton, narrow neck section modulus (r 0.4; P < 0.001 in men and r 0.37; 2 P < 0.001 in women); intertrochanteric section modulus (r ¼ 0.46; Southampton, UK and Department of Epidemiology and P < 0.001 in men and r ¼ 0.48; P < 0.001 in women) and femoral Biostatistics, EMGO Institute for Health and Care Research, shaft section modulus (r ¼ 0.54; P < 0.001 in men and r ¼ 0.60; Amsterdam, The Netherlands P < 0.001 in women). Conclusion: To our knowledge this is the first time that HSA and Background: Epidemiological studies of knee OA have often used a pQCT have been directly compared. The results of this study show radiographic definition. However, the clinical syndrome of OA is that there are strong correlations between two measures of bone influenced by a broad range of factors in addition to the structural strength of the lower limb, HSA and pQCT. changes required for radiographic OA. Hence more recently several Disclosure statement: The authors have declared no conflicts of studies have adopted a clinical or self-reported approach to OA interest. diagnosis rather than a radiographic approach. The aim of this study was to investigate agreement between radiographic OA and the clinical and self-reported diagnoses of OA. 037. PROGNOSTIC FACTORS FOR LONG-TERM Methods: Data were available for 199 men and 196 women who PROGRESSION OF HAND PAIN AND FUNCTION IN participated in the UK component of the European Project on SYMPTOMATIC PERSONS AGED OVER 50 YEARS, WITH, OR Osteoarthritis (EPOSA) and, who originally participated in the AT RISK OF, HAND OSTEOARTHRITIS Hertfordshire Cohort Study (HCS), UK. Participants completed a nurse administered questionnaire detailing self-reported OA. A clinical Elaine Nicholls1, Elaine Thomas1, Danielle van der Windt1 and diagnosis of OA was defined based on ACR criteria using history and George Peat1 examination findings. Knee radiographs were taken and graded for 1Research Institute for Primary Care & Health Sciences, Keele overall Kellgren–Lawrence score. To assess the strength of agreement University, Keele, UK between the radiographic and clinical definitions of OA, and between radiographic and self-reported definitions of OA, sensitivity, specificity Background: Longitudinal data can provide information to patients and relative risk statistics were calculated. This study used a and clinicians on disease prognosis, however, such information is radiographic diagnosis of OA as the gold standard. Sensitivity was lacking for older adults with hand OA. This analysis aimed to identify defined as the proportion of those with radiographic diagnosis of OA combinations of factors that predict progression of hand pain and who also had a positive OA diagnosis according to the alternative functional difficulty over time in older adults with, or at high risk of, definition of interest (i.e. clinical or self-reported). Specificity was hand OA. defined as the proportion of those with a negative radiographic Methods: Participants were recruited to the Clinical Assessment diagnosis of OA who also had a negative OA diagnosis according to Study of the Hand (CAS-HA), a prospective population-based cohort the alternative definition of interest. of adults aged 50 years and over reporting hand pain in the last 12 Results: The mean (S.D.) age of study participants was 75.2 (2.6) years. months at baseline. The AUSCAN Pain and Function subscales (each The prevalence of knee OA differed depending on the method converted to a 0–10 scale) were measured at baseline and four follow- employed for diagnosis; 21% of the study participants’ self-reported up time points (1.5, 3, 5 and 7.5 years) and used as separate outcomes knee OA, 18% of the participants had clinical knee OA and 42% of the in two random effects models to determine progression of hand pain participants had radiographic OA. Of those 72 study participants with and functional difficulty over time. A multi-stage selection process, a self-reported diagnosis of knee OA 52 (72%) had a radiographic incorporating forwards and backward selection, was used to select diagnosis of knee OA, while 66% (39 out of 59) of study participants prognostic factors that predict outcome progression over time. with clinical knee OA had a diagnosis of radiographic knee OA. Baseline factors included demographic, lifestyle, health, psychological However 58% of those participants diagnosed with radiographic OA measures along with measures of the participants’ hand condition did not have either self-reported knee OA or a diagnosis of clinical OA. including the number of joints with radiographic hand OA. All models Therefore in comparison with the radiographic definition of OA, both were estimated using full-information maximum likelihood to handle the clinical and self-report definitions had high specificity (91.5% and missing data. 91.5% respectively) and low sensitivity (24.5% and 32.7% Results: A total of 623 participants were recruited to the CAS-HA respectively). study (mean age 64 (S.D. 8.2) years, 62% female). Follow-up rates were Conclusion: There is modest agreement between the radiographic, 96%, 91%, 71% and 66% at each follow-up time point, respectively. clinical and self-report methods of diagnosis of knee OA. i64 Tuesday 28 April 2015 POSTER VIEWING I

Disclosure statement: C.C. has received consulting fees from University Hospitals NHS Foundation Trust, Manchester, Servier, Eli Lilly, Merck, Amgen, Alliance, Novartis, Medtronic, GSK 3Department of Public Health and Primary Care, University of and Roche. All other authors have declared no conflicts of interest. Cambridge School of Clinical Medicine, Cambridge and 4Norwich Medical School, University of East Anglia, Norwich, UK 039. MORTALITY IN SYSTEMIC LUPUS ERYTHEMATOSUS IN THE UK 1999–2012 Background: Lifestyle predictors of developing inflammatory poly- arthritis have previously been studied in the European Prospective Frances Rees1,2, Michael Doherty1, Matthew Grainge3, Investigation of Cancer, Norfolk (EPIC-Norfolk) population through Peter Lanyon1,2, Graham Davenport4 and Weiya Zhang1 linkage with the Norfolk Arthritis Register (NOAR). Metabolic predictors 1Division of Rheumatology, Orthopaedics and Dermatology, of inflammatory polyarthritis have not been as well characterized and University of Nottingham, 2Rheumatology, Nottingham University have not been considered alongside lifestyle factors. We considered Hospitals NHS Trust, 3Division of Epidemiology and Public Health, addition of metabolic factors to an established multivariate lifestyle University of Nottingham, Nottingham and 4Arthritis Research UK factor model, with updated record linkage between EPIC-Norfolk and Primary Care Centre, Keele University, Keele, UK NOAR. Methods: Data on lifestyle factors in the established model (pack- Background: SLE is a chronic multi-system autoimmune disease years of smoking (adjusted for never being a smoker), smoking status, which is associated with significant mortality. Four studies have alcohol consumption (adjusted for being a teetotaller), BMI, socio- estimated mortality in people with SLE in the UK, but only two economic status, self-reported diabetes mellitus, parity and duration of compared mortality with the general population. Hochberg (1987) breast feeding) was collected by questionnaire at entry to EPIC- found that men and women with SLE were respectively 39 and 154 Norfolk. Measures of metabolic factors [serum uric acid, high-density times more likely to die at any given age compared with people without lipoprotein cholesterol, Apo-A1, Apo-B and HbA1c (glycated haemo- SLE. Moss et al. (2002) estimated the increased risk of death to be 4.0 globin)] were made on a non-fasting blood sample taken at the same (95% CI 2.8, 5.2) times the general population. We aimed to estimate time. Participants in EPIC-Norfolk who subsequently developed the mortality associated with SLE in the UK during the period inflammatory polyarthritis were identified via linkage with NOAR, a 1999–2012 including variation with age, gender and region. primary care based inception cohort study of early inflammatory Methods: A retrospective cohort study was conducted using the UK polyarthritis. Associations between the metabolic risk factors and Clinical Practice Research Datalink, a longitudinal database of incident inflammatory polyarthritis were assessed using multivariate anonymized general practice records deemed to be representative Cox proportional hazards models, first univariately, then adjusted for of the UK population. Incident SLE cases were identified during the age and gender, and finally by adding the individual predictors to the period 1999–2012 and matched by age, sex and practice to four existing multivariate Cox models, one for all participants (with an controls. The case fatality rate was estimated by dividing the number interaction term for gender and pack-years of smoking) and one just of incident cases who died during the study period by the number of for females. Subjects were followed until development of inflammatory person-years since diagnosis and expressed per 1000 person-years. polyarthritis, death (ascertained through linkage with the UK Office for Sex, age and region-specific fatality rates were calculated and National Statistics), loss to follow up or May 2014, whichever came compared with controls using incidence rate ratios (IRRs). For first. Associations were assessed at the 5% significance level. individuals attending English general practices with linked Office of Results: Data were available on 25 636 subjects (55% female), National Statistics (ONS) data, cause of death was summarized by the including 231 incident cases of inflammatory polyarthritis (66% ICD-10 chapter heading. female). Median age at entry to EPIC-Norfolk was 59 years Results: Of 2740 incident cases diagnosed during 1999–2012 (85% (interquartile range 51–67), median follow up was 214 months (198– female, mean age 48.9 years), 227 died giving a case fatality rate of 230) and median time to onset of inflammatory polyarthritis was 79 15.84/1000 person-years (95% CI 13.91, 18.04). This was 67% higher months (34–136). No significant association was observed between than controls (IRR 1.67, 95% CI 1.43, 1.94, P < 0.001). The case fatality incident inflammatory polyarthritis and serum uric acid, HDL-C, Apo-A rate for females with SLE was half that of males (IRR: 0.54, 95% CI or Apo-B. Baseline HbA1c was positively associated with developing 0.40, 0.73, P < 0.001). However, compared with controls the fatality inflammatory polyarthritis in univariate analysis [hazard ratio (HR) 1.22, rate for males with SLE was 1.80 times that of male controls (95% CI 95% CI (1.03, 1.44)], when adjusted for sex and age [HR 1.27 (1.08, 1.32, 2.45, P < 0.001) and for females was 1.64 times higher (95% CI 1.49)] and when added to the existing multivariate lifestyle factor 1.37, 1.96, P < 0.001). The age-specific fatality rates increased models for all [HR 1.26 (1.07, 1.47)] and just for females [HR 1.23 (1.00, significantly with age, however, the IRR diminished from 3.81 (95% 1.52)]. However, inclusion in the multivariate model led to self-reported CI, 1.43, 10.14) in those <40 years to 0.82 (95% CI 0.36, 1.83) in those DM no longer having a significant positive association with inflamma- 90 years. There was no significant difference in mortality between tory polyarthritis. regions. For both cases and controls with linked ONS data (57%), Conclusion: Baseline HbA1c was found to be a predictor of incident circulatory system disease and malignancy were the most frequent inflammatory polyarthritis, and at the expense of self-reported causes of death. diabetes mellitus when included in an established multivariate lifestyle Conclusion: People with SLE have higher mortality than matched factor model. While diabetes mellitus is an established risk factor for controls. Men with SLE had twice the risk of death as women with SLE inflammatory polyarthritis, HbA1c levels may capture additional risk but this is in part due to the increased mortality in males in general. information on those in a prediabetic state and could prove a more Those at younger ages had the greatest risk compared with controls. sensitive marker of future inflammatory polyarthritis. Region did not impact on mortality. Circulatory system disease and Disclosure statement: The authors have declared no conflicts of malignancy were the most frequent causes of death. interest. Disclosure statement: M.D. has received personal fees from ad hoc advisory boards for gout and OA for AstraZeneca, Menarini, Nordic 041. ANTI-CITRULLINATED PROTEIN ANTIBODY STATUS Biosciences, Novartis and Pfizer outside of the submitted work. P.L. IN THE GENERAL POPULATION AND AS A PREDICTOR has served on speakers’ bureaus on behalf of Pfizer; and has served OF FUTURE INFLAMMATORY POLYARTHRITIS: THE on the advisory board for Eli Lilly. G.D. has received personal fees from EPIC-2-NOAR STUDY advisory boards and presentations at meetings from MSD, Pfizer, Lilly, Menarini, Servier, Prostrakan, Amgen, GSK and Consilient. W.Z. has Suzanne M. Verstappen1, Jamie C. Sergeant2, Robert N. Luben3, received honoraria from Savient for Pegloticase and from Daiichi Amit Bhaniani3, Serena Anuj3, RA-MAP consortium, Sankyo for topical loxoprofen patches. All other authors have declared Alex J. MacGregor4, Nick Wareham3, Deborah P. M. Symmons1,2, no conflicts of interest. Kay-Tee Khaw3 and Ian N. Bruce1,2 1Arthritis Research UK Centre for Epidemiology, The University of Manchester, 2NIHR Manchester Musculoskeletal Biomedical 040. COMBINING LIFESTYLE AND METABOLIC Research Unit, Manchester Academic Health Science Centre, PREDICTORS OF INCIDENT INFLAMMATORY 3 POLYARTHRITIS IN THE EPIC-2-NOAR STUDY Manchester, European Prospective Investigation into Cancer and Nutrition, Department of Public Health and Primary Care, Jamie C. Sergeant1,2, Suzanne M. M. Verstappen1, Strangeways Research Laboratory, University of Cambridge, Catharine Morgan1, Robert N. Luben3, Amit Bhaniani3, Serena Anuj3, Cambridge, 4Rheumatology, Norfolk and Norwich University RA-MAP consortium, Alex J. MacGregor4, Nick Wareham3, Hospital, Manchester, UK Deborah P. M. Symmons1,2, Kay-Tee Khaw3 and Ian N. Bruce1,2 1Arthritis Research UK Centre for Epidemiology, Centre for Background: ACPA immune response occurs several years prior to Musculoskeletal Research, Manchester Academic Health Science the diagnosis of RA. However, limited data are available on ACPA Centre, University of Manchester, 2NIHR Manchester status in the general population compared with those who develop RA Musculoskeletal Biomedical Research Unit, Central Manchester or inflammatory polyarthritis in the future. The aim of this study was to POSTER VIEWING I Tuesday 28 April 2015 i65

examine ACPA status in the general population and in patients information was used. BMI (in kg/m2) was classified into normal BMI, developing inflammatory polyarthritis and RA. overweight (BMI 25–30), obese (30–40) and morbidly obese (>40). Methods: ACPA was measured by ELISA (Euro-Diagnostica) in stored Weight change over time was estimated using generalized estimating serum samples collected at baseline in people participating in the equations with adjustment for baseline weight. European Prospective Investigation of Cancer in Norfolk (EPIC- Results: Data were available from 585 patients [mean age 61 (S.D. 16), Norfolk), a prospective population-based study in the UK. In addition 78% female, mean disease duration 7 years (interquartile range 4–13)]. to ACPA status (positive >25 U/ml) data on age, gender, socio- In total, 64% of patients had above normal BMI (overweight 31%, economic status (i.e. manual/unskilled worker, manager/skilled non- obese 27%, morbidly obese 6%). Individual patient weight increased manual worker, professional), smoking status (i.e. never, former, by 0.19 kg/year (95% CI 0.01, 0.36). There were no significant current) were also collected at inclusion. Individuals who subsequently differences in age, gender, disease duration or prednisolone use developed inflammatory polyarthritis and RA were identified by linkage across BMI categories (Table 1). Increasing BMI associated with with the Norfolk Arthritis Register (NOAR), a primary care based cohort higher disability and higher disease activity. The greatest mean with an overlapping catchment area. Logistic regression analyses were differences were for tender joint counts and patient global scores. used to assess the association between demographic characteristics Inflammatory markers were significantly higher, although differences and ACPA positivity in the general population. Cox regression analyses were less marked for CRP than ESR. Low disease activity states were were performed to assess the association between ACPA and the uncommon in patients with higher BMI: odds ratio for low disease development of inflammatory polyarthritis, adjusting for age and activity in obese patients compared with non-obese 0.39 (95% CI gender. Patients with a symptom onset prior to inclusion in EPIC- 0.27, 0.56). Norfolk were excluded from the Cox regression analysis (n ¼ 104). In Conclusion: Excess body weight is prevalent in RA and patients addition, the interaction between ACPA and smoking was tested. continue to gain weight year-on-year. However, it is unclear whether People were followed until development of inflammatory polyarthritis the relationship between obesity and poorer outcome is attributable to and RA or censored at date of death or May 2014, whichever came increased inflammatory burden that would be responsive to immuno- first. suppression. The data presented here show higher DAS is driven by Results: ACPA was measured in 18 577 EPIC participants aged 40–79 tender rather than swollen joint counts, which may reflect pain years. ACPA was positive in 429 subjects (2.30%) in the general sensitization rather than autoimmunity. This could explain the lack of population including 104 patients with prevalent inflammatory poly- association between obesity and erosive disease, despite strong arthritis and RA (35.6% ACPA positive) and 173 (16.8% ACPA- correlations with other disease measures. Irrespective, DAS remission positive) subjects who developed inflammatory polyarthritis during is rare in obese patients and may not be a realistic target. 311 051 person-years of follow up. Cross-sectionally, current and Disclosure statement: The authors have declared no conflicts of former smokers [odds ratio (OR) 1.60 95% CI 1.95, 2.13 and OR 1.29 interest. 95% CI 1.02, 1.55, respectively] and older age (OR 1.01 95% CI 1.00, 1.03) were associated with ACPA positivity. Gender and socio- economic status were not associated with ACPA. Of 173 patients 043. THE PREVALENCE OF GIANT CELL ARTERITIS AND who developed inflammatory polyarthritis and were notified to NOAR, POLYMYALGIA RHEUMATICA IN A UK PRIMARY CARE 85 (49.4%) fulfilled the 2010 ACR/EULAR criteria for RA at entry to the POPULATION

NOAR cohort. ACPA status was predictive for the development of 1,2 2 3 inflammatory polyarthritis and RA (adjusted hazard ratio 10.3 95% CI Max Yates , Karly Graham , Richard A. Watts and Alex J. MacGregor1 6.90, 15.34). The interaction between ACPA and smoking was not 1 2 significant. Rheumatology, Norfolk and Norwich University Hospital, Norwich Conclusion: Medical School, University of East Anglia, Norwich and ACPA was positive in 2.1% of a general population 3 sample aged 40–79 years old. People who were ACPA positive were Rheumatology, Ipswich Hospital, Ipswich, UK 10 times more likely to develop inflammatory polyarthritis and RA in the next 3–10 years than those ACPA-negative subjects. ACPA may be a Background: Accurate population prevalence estimates for PMR and useful adjunct to other screening approaches to identify people at GCA are essential for health service planning. However the only data higher risk of developing inflammatory polyarthritis and RA. available in the UK are outdated; and estimates for other countries are Disclosure statement: The authors have declared no conflicts of based on different methods of case ascertainment and classification interest. and vary widely. The aim of this study was provide updated prevalence figures for these conditions in the in the UK based on cases ascertained from primary care and using current definitions. 042. THE ASSOCIATION BETWEEN OBESITY AND DISEASE Methods: Clinical data was obtained from practice records of a large ACTIVITY IN RHEUMATOID ARTHRITIS general practice in Norfolk, UK. Case records were reviewed for the purposes of diagnosis and classification of GCA and PMR. To ensure Megan Whittaker1, Nicola Gullick2, Sophia Steer2, Savia de Souza1, that there was not a substantial undiagnosed disease burden within Lindsay Bearne1, Julia Darzi1, David Scott1, Heidi Lempp1 and the practice population, the practice population aged 55 years or older James Galloway1 was surveyed using a questionnaire designed using published cardinal 1Rheumatology, King’s College London and 2Rheumatology, King’s features of GCA and PMR. Non-responders were sent reminders after College Hospital, London, UK 3 months. Questionnaire responses were risk-stratified for potential diagnoses of GCA and PMR and those at high risk reviewed by a Background: Obesity is both a risk factor for RA and associated with rheumatologist. worse outcomes. Studies have demonstrated that high BMI is Results: A total of 6159 patients registered with the practice aged 50 associated with higher disease activity, disability and poorer treatment years and older. Of these, 22 had a diagnosis of GCA and 117 had a responses, although not erosive progression. The aim of the current diagnosis of PMR in their care record. A survey was sent to all eligible study is to assess prevalence and time trends of obesity in a single- individuals aged 55 years or older (exclusion criteria included those centre inner-city RA cohort and examine the relationship between BMI with terminal illness, dementia or living in a nursing home). 2227 and disease activity components. completed questionnaires were returned from the population of 4728 Methods: Routinely captured data from RA patients electronic health (97.2% with complete data). The median age of the respondents was records were retrospectively studied. DAS, disability (HAQ), and BMI 68 years (interquartile range 12 years), 52% were female. There were were collected at each clinic visit. Patients’ most recent clinic visit no statistical differences between the median age and gender ratio

042 TABLE 1. Characteristics of disease activity across BMI categories Characteristic All (n ¼ 585) Normal BMI (n ¼ 10) Overweight (n ¼ 181) Obese (n ¼ 160) Morbidly obese (n ¼ 34) P-value

HAQ, mean (S.D.) 1.4 (0.9) 1.2 (0.9) 1.4 (0.9) 1.6 (0.9) 1.7 (0.9) 0.0017 DAS, mean (S.D.) 3.8 (1.6) 3.5 (1.6) 3.7 (1.6) 4.3 (1.5) 4.7 (1.3) <0.0001 ESR, mean (S.D.), mm/h 25 (22) 22 (21) 23 (21) 28 (21) 33 (24) 0.0004 CRP, mean (S.D.), mg/l 11.8 (18.2) 12.3 (21.4) 10.2 (17.2) 12.1 (15.1) 14.8 (15.3) 0.0011 TJC, mean (S.D.) 5.4 (7.1) 4.3 (6.6) 4.9 (6.6) 7.0 (8.0) 7.8 (7.2) 0.0001 SJC, mean (S.D.) 1.9 (3.0) 1.8 (3.0) 1.7 (3.0) 2.2 (2.9) 1.7 (2.7) 0.1814 Patient global 46 (27) 41 (26) 42 (25) 54 (27) 59 (26) 0.0001 Low disease activitya, n (%) 227 (39) 100 (48) 81 (45) 40 (25) 6 (18) <0.0001 Overweight: BMI 25–29.9; obese: BMI 30–39.9; morbidly obese: BMI >40. aLow disease activity defined as DAS28 <3.2. DAS28: DAS for 28 joints; SJC: swollen joint count; TJC: tender joint count. i66 Tuesday 28 April 2015 POSTER VIEWING I

between responders and non-responders. During the time of the study no participants were identified with a new diagnosis of GCA and no new diagnoses of GCA were made at the practice. 15 participants self- PRIMARY CARE reported a diagnosis of GCA (8 of who were confirmed by the practice) and 83 self-reported a diagnosis of PMR (73 confirmed by the practice). The resulting minimum prevalence estimates for those aged >55 years were 17/10 000 (95% CI 5, 29) for GCA and 154/10 000 045. WHAT DOES A PRIMARY CARE ANNUAL REVIEW FOR (95% CI 119, 190) for PMR. RHEUMATOID ARTHRITIS INCLUDE? A NATIONAL GENERAL Conclusion: This is the first prevalence estimate of GCA for the UK PRACTITIONER SURVEY for 30 years and the first to apply current classification criteria. Samantha Hider1,2, Milica Blagojevic-Bucknall1, Rebecca Case1, Community-derived estimates of prevalence are likely to be most Kris Clarkson1, Rebecca Stack3, Karim Raza3 and Christian representative of true disease burden. D. Mallen1 Disclosure statement: The authors have declared no conflicts of 1 Research Institute for Primary Care & Health Sciences, Keele interest. University, Keele, 2Rheumatology Department, Haywood Rheumatology Centre, Staffordshire & Stoke-on-Trent Partnership 044. CLUSTERING OF LIFESTYLE RISK FACTORS AND LOW NHS Trust, Stoke-on-Trent and 3Rheumatology Research Group, BONE DENSITY IN OLDER ADULTS: THE HERTFORDSHIRE School of Immunity & Infection College of Medical & Dental Sciences, COHORT STUDY University of Birmingham, Birmingham, UK

1 1 1 1 Jean Zhang , Karen Jameson , Avan Aihie Sayer , Sian Robinson , Background: NICE standards of care for RA recommend a holistic Cyrus Cooper1,2 and Elaine Dennison1,3 1 annual review including assessment of disease activity and severity MRC Lifecourse Epidemiology Unit, University of Southampton, and active screening for comorbidities. In England, RA was included in Southampton, 2NIHR Musculoskeletal Biomedical Research Unit, 3 the Quality Outcomes Framework in 2013 with general practitioner University of Oxford, Oxford, UK and Victoria University, Victoria (GP)s incentivized to provide an annual face to face review for RA University, Wellington, New Zealand patients which should include cardiovascular and fracture risk screening. The aim of this study was to examine what GPs include Background: Lifestyle factors are associated with BMD, which in turn in an annual review for patients with RA. is strongly linked with risk of fragility fracture. Since clustering of Methods: 5000 GPs across England were randomly selected from the adverse lifestyle factors might occur in some individuals, we examined Binley’s database and mailed a cross-sectional questionnaire which the relationship between a number of lifestyle risk factors (low physical investigated primary care management of RA. Ethical approval for the activity, poor diet, smoking, high alcohol intake, low grip strength, study was obtained from Keele University. personal and family history of prior fracture) and BMD in a population Results: 1388 completed questionnaires were returned. The mean of older community dwelling men and women. (S.D.) age of responders was 47 (9.4) years. 705 (60%) were female and Methods: We studied 498 men and 498 women aged 59–72 years, 1052 (76.3%) indicated that they were a GP partner. Half of GPs felt who were participants in the Hertfordshire Cohort Study. Physical that RA should be included in the quality and outcomes framework activity, diet quality, history of prior fracture, family history of fracture, (QOF), although only 939 (67.8%) indicated they were aware of the cigarette smoking and alcohol consumption were obtained through NICE Standards of Care for RA. The majority of GPs (1139, 82.1%) questionnaire. We also recorded information on comorbidities: included cardiovascular risk assessment, although this was performed bronchitis, diabetes, ischaemic heart disease, hypertension and by practice nurses in 50% of cases. Fracture risk assessment was also stroke. Grip strength was measured by hand held dynamometer. common (1118, 80.5%); this was usually performed by GPs them- Diet in the lower quarter of the prudent diet distribution was classified selves (1023, 73.7%). GPs were less confident in assessing RA as poor diet; high alcohol intake equated to an intake greater than the disease activity (556, 40%), disease complications (329, 24%) and UK recommended number of units per week, low grip strength was routine use of the DAS for 28 joints was uncommon (27, 2%). 767 defined as <30 kg for men and <20 kg for women, and low activity was (55%) of GPs thought their patients had access to an annual review in defined as a score of <50. Bone density of the lumbar spine and total secondary care. femur were obtained using a Hologic QDR 4500 instrument. In 314 Conclusion: Including RA in the GP QOF encourages GPs to men and 318 women, we also had available data on incident fracture a provide screening for cardiovascular disease and osteoporosis mean of 8.4 years after baseline data collection. only, and whether this will continue now RA is removed from the Results: In women, we observed a graded association between QOF is unclear. However, the more RA specific components of number of risk factors and bone density at the lumbar spine and total annual review such as disease activity, mobility assessment and femur, as shown in Table 1. Among women strong relationships were medication review still largely happen in secondary care. Good seen between number of risk factors and incident fracture; women communication systems are needed across the healthcare setting to with three or more risk factors had an adjusted hazard ratio (HR) of avoid duplication of screening and fragmenting of care for these incident fracture of 5.98 (95% CI 1.67, 21.43; P ¼ 0.006) compared patients. with women without risk factors. While women with two risk factors Disclosure statement: M.B.-B. has received research funding had an adjusted HR of 2.97 (95% CI 1.14, 7.74; P ¼ 0.03) and those from the NIHR School for Primary Care Research. C.D.M. has with one, 2.28 (95% CI 0.90, 5.75; P ¼ 0.08). In men, relationships received grants/research support from the NIHR. The views appeared similar but were statistically non-significant. expressed are those of the author(s) and not necessarily those of Conclusion: We have shown that clustering of lifestyle factors the NHS or the NIHR. All other authors have declared no conflicts adversely related to bone health occurs, and is associated with both of interest. reduced bone density and increased rates of fracture. Health education programmes may play an important role in educating the population about their lifestyle choices, and reduce these risks. Disclosure statement: C.C. has received consulting fees from Servier; Eli Lilly; Merck; Amgen; Alliance; Novartis; Medtronic; GSK and Roche. All other authors have declared no conflicts of interest.

044 TABLE 1. Relationship between number of risk factors and bone density of total femur and lumbar spine Total femur Lumbar spine Adjusteda (n ¼ 473) Adjusteda (n ¼ 473)

Number of risk factors Regression coefficient 95% CI P-value Regression coefficient 95% CI P-value 0 (reference) 0 (0.000, 0.000) — 0 (0.000, 0.000) — 1 0.129 (–0.078, 0.336) 0.223 0.115 (–0.096, 0.327) 0.285 2 0.223 (–0.014, 0.460) 0.065 0.255 (0.013, 0.497) 0.039 3þ 0.758 (0.392, 1.124) <0.001 0.531 (0.157, 0.905) 0.005 aFor age and number of comorbidities (bronchitis, diabetes, ischaemic heart disease, hypertension and stroke). POSTER VIEWING I Tuesday 28 April 2015 i67

046. INTEGRATING CARE FOR JOINT PAIN AND ANXIETY Development of Research in Primary Care (SIDIAP) in a retrospective AND DEPRESSION INTO REVIEWS FOR LONG-TERM cohort study. SIDIAP is an electronic database with clinical information CONDITIONS: THE ENHANCE STUDY from the primary care records of more than five million people 1 1 1 representing 80% of the Catalonian population aged 14 years. Clare Jinks , Andrew Morden , Carolyn Chew-Graham , Methods: We included patients 18 years who were tested for RF Mark Porcheret1, Andrew Finney1, Krysia Dziedzic1, 1 1 1 1 from 1 January 2006 to 31 December 2011.From this population, we Emma L. Healey , Valarie Tan , Vince Cooper , Joanne Jordan and identified patients with an incident GP-coded diagnosis of RA in the Christian D. Mallen1 1 year following RF testing (from 1 January 2006 to 31 December 2012). Research Institute for Primary Care & Health Sciences, University of We excluded participants with RA diagnosed >1 year after RF testing. Keele, Keele, UK We calculated the sensitivity, specificity, likelihood ratios and predictive values for RF, ESR and CRP. We used receiver operating Background: Joint pain and mental health problems are common and characteristic(ROC) curves for RF, ESR and CRP against an incident often co-exist with other long-term conditions (LTCs), but are under- diagnosis of RA made in the following year and estimated the areas detected and sub-optimally managed in primary care. The aim of the under the ROC curve (95% CI) to identify the best theoretical ENHANCE study is to develop and test the feasibility and acceptability thresholds. We estimated age and gender-adjusted odds ratios (OR) of a practice nurse-led enhanced LTC review for identifying, assessing for a diagnosis of RA in the year following RF testing using the Mantel– and supporting the management of joint pain, anxiety and/or Haenszel test. We calculated the total cost of RF testing during the depression in patients attending routine LTC reviews. We report on study period and the cost per true positive RA. the development of the new complex intervention. Results: From a population of 4 796 498, we found that 495 434 Methods: An implementation of change model was used which had patients (10.3%) were tested for RF at least once during the study three parts. The first is an evidence synthesis followed by a community period at an estimated cost of E3 963 472. Of these, 1 07 362 (21.7%) of practice to co-produce a concrete proposal for the intervention. A were RF positive, of whom 2768 (2.6%) were diagnosed with RA within community of practice is a method for collaborative learning leading to 12 months, compared with 1141/388 072 (0.3%) of the RF(-) creation and management of new knowledge and practice develop- participants subsequently diagnosed with RA. The best theoretical ment. For this study it consisted of patient and practice nurse advisory cut-off value for RF was 13.4 IU/ml, for ESR was 24 mm/h and for CRP groups and three stakeholder workshops. The second is a target was 0.53 mg/dl. At this cut-off, RF had a sensitivity of 65.4% (95% CI group analysis using a focus group with practice nurses (n ¼ 6) to 63.9, 66.9), specificity 88.7% (95% CI 88.6, 88.8) and positive and identify current practice and potential determinants of behaviour negative likelihood ratios of 5.78 (95% CI 5.65, 93) and 0.39 (95% CI change required to deliver the new intervention. Data were analysed 0.37, 0.41) respectively. Age and gender-adjusted OR for a diagnosis thematically and then mapped to the Theoretical Domains Framework. of RA in the year following RF testing was 13.8 (12.8–15.0) for the The third part includes training needs and techniques to address theoretical threshold of 13.4 IU/ml. The cost of testing per RF-positive determinants of nurse behaviour highlighted in part 2 were identified case of RA was E1432. and integrated into the training programme for the trial. Ethical Conclusion: 10.3% of the study population were tested for RF, but approval was gained for the focus group. only 2.6% of RF-positive patients were subsequently diagnosed with Results: Through collaborative working an algorithm for the enhanced RA, indicating that it is tested in many patients with a poor pre-test review was produced which includes tools for case finding and further probability of RA in primary care. The high cost of testing (E1432 per assessment, evidence-based treatment options (e.g. based on NICE RF-positive case of RA could be reduced by targeting patients with a guidelines) and signposting options to other services and third sector. greater likelihood of RA, based on clinical features. In the focus group practice nurses understood the new complex Disclosure statement: N.A. has received consulting fees from Flexion intervention but highlighted potential treatment burden for patients (PharmaNet), Lily, Merck, Q-Med, Roche and Smith & Nephew; has receiving the review. Issues related to capabilities and professional received research grants from Novartis, Pfizer, Schering-Plough and roles were evident as they talked of a lack of knowledge, confidence Servier. C.C. has received consulting fees from Amgen, GSK, the and skills to undertake OA case finding, joint assessments and initial Alliance for Better Bone Health, MSD, Eli Lilly, Pfizer, Novartis, Servier, management. Practice nurses were more confident in asking about Merck, Medtronic and Roche; has received honoraria from Amgen, anxiety and depression but disclosed avoidance of this activity in Alliance for Better Bone Health, Eli Lilly, Novartis, Merck, GSK, MSD, practice. In addition to knowledge, confidence and skills for dealing Pfizer, Servier, Medtronic and Roche; and has received lecture fees with OA, training needs in detecting non-verbal cues which might from Amgen, Alliance for Better Bone Health, Eli Lilly, Novartis, Merck, suggest anxiety and/or depression were highlighted, as were MSD, Servier, Medtronic and Roche, GSK, Pfizer. D. R.A.L. has strategies for providing reassurance about their decisions (and received consulting fees from GSK, ROCHE, Novartis and Pfizer. All consequences) and emotional support or supervision during the other authors have declared no conflicts of interest. intervention period. Conclusion: An implementation of change model has been applied using an evidence synthesis, community of practice and focus group with practice nurses. This approach has enabled co-design of a new 048. A NEGATIVE RHEUMATOID FACTOR RESULT IN complex intervention for integrating joint pain and anxiety and/or PRIMARY CARE SIGNIFICANTLY DELAYS THE TIME TO depression into LTC reviews in primary care consultations and DIAGNOSIS OF RHEUMATOID ARTHRITIS: A STUDY USING identification of training needs. A feasibility stepped wedge trial will THE CLINICAL PRACTICE RESEARCH DATALINK commence in 2015. Alison L. Nightingale1, Anne Miller2, Cormac J. Sammon1, Kamal Disclosure statement: The authors have declared no conflicts of 3 3 1 4 interest. R. Mahtani , Tim A. Holt , Neil J. McHugh and Raashid A. Luqmani 1Department of Pharmacy & Pharmacology, University of Bath, Bath, 2Department of Rheumatology, Oxford University Hospitals NHS 3 047. RHEUMATOID FACTOR TESTING IN SPANISH PRIMARY Trust, Nuffield Department of Primary Health Care Sciences, 4 CARE COSTS E1432 PER TRUE POSITIVE CASE OF University of Oxford and Nuffield Department of Orthopaedics, RHEUMATOID ARTHRITIS; A STUDY USING ELECTRONIC Rheumatology & Musculoskeletal Science, University of Oxford, DATA FROM THE INFORMATION SYSTEM FOR THE Oxford, UK DEVELOPMENT OF RESEARCH IN PRIMARY CARE Background: Early treatment of patients with RA is important to 1 2 3 Klara Morsley , Anne Miller , Christopher J. Edwards , prevent long-term joint damage and disability. Many general practi- 4 4 5 Kassim Javaid , Rafael Pinedo-Villanueva , Manuel Medina Peralta , tioners (GPs) undertake RF testing to distinguish early RA from a larger 5 4 5 Sebastian Calero Munoz , Nigel Arden , Francesc Fina-Aviles , number of patients with non-inflammatory joint pain. The aim of the 4 4 4 Cyrus Cooper , Daniel Prieto-Alhambra and Raashid A. Luqmani study was to examine the impact of negative RF tests on time to RA 1 2 Wexham Park Hospital, Slough, Nuffield Orthopaedic Centre, diagnosis between 2000 and 2010 using the UK Clinical Practice 3 Oxford University Hospitals NHS Trust, Oxford, NIHR Wellcome Research Datalink (CPRD). Trust Clinical Research Facility, Southampton University Hospital Methods: Incident cases of RA, with at least 2 years of data in their Southampton, Southampton, 4NIHR Musculoskeletal Biomedical record before diagnosis, were identified from the CPRD using a Research Unit, Oxford University Hospitals NHS Trust and the previously validated algorithm. We identified all RF tests in the 2 years University of Oxford, Oxford, UK and 5Institut Catala´ de la Salut, before diagnosis and classified them as positive or negative based on Institut Catala´ de la Salut, Barcelona, Spain the recorded upper value for the normal range (UNR). Where there was a record of an RF test but no titre recorded, tests were classified as Background: RF is commonly tested in primary care to support or having a missing test result. The time from first RF test to RA diagnosis exclude a diagnosis of RA. We investigated the utility of RF in the was calculated for each patient. Kaplan–Meier survival curves were diagnosis of RA in primary care using the Information System for the constructed, stratified by RF test result, age at RA diagnosis (<50, i68 Tuesday 28 April 2015 POSTER VIEWING I

50–70 and >70 years) and sex. The equality of the survival functions innovation will be shared and distributed across the West Midlands were compared using Log Rank tests. AHSN. Results: There were 14 761 incident cases (4610 males and 10 151 Disclosure statement: The authors have declared no conflicts of females) of RA during the study period. 8314 (56.3%) of patients had at interest. least one RF test in the 2 years before diagnosis; 39.8% of tests were positive, 19.5% were negative and 40.7% had no RF titre recorded. 050. HOW COMMON IS DEPRESSION IN PATIENTS WITH The median time from first RF test to RA diagnosis was 2.2 months POLYMYALGIA RHEUMATICA? (95% CI 2.0, 2.3) in patients with a positive test. In those with a negative or missing test result the median times to diagnosis were 3.7 Arani Vivekanantham1, Milica Bucknall1, Kris Clarkson1, months (95% CI 3.5, 4.0) and 3.2 months (95% CI 3.0, 3.4) respectively Irena Zwierska1, Christian Mallen1 and Samantha L. Hider1,2 (P < 0.0001). Time from first RF test to RA diagnosis was shorter in 1Arthritis Research UK Primary Care Centre, Research Institute for males than in females (P < 0.001) and in patients aged 50–70 years at Primary Care and Health Sciences, Keele University, Keele and RA diagnosis compared with those aged <50 or >70 at diagnosis (P 2Rheumatology Department, Haywood Rheumatology Centre, <0.0001).Kaplan–Meier curves were similar for patients with negative Staffordshire and Stoke-on-Trent Partnership Trust, Staffordshire, and missing test results. UK Conclusion: Approximately half the patients with an eventual diagnosis of RA had a record of RF testing in primary care. Background: PMR is a common inflammatory disorder of older (>50 However, a negative RF test in primary care resulted in a significant years) adults, frequently managed in primary care. Other rheumatic delay in diagnosing RA. Negative RF tests should not be used to rule disorders, such as RA, are associated with an increased risk of out RA and GPs should be encouraged to refer patients on the basis of depression which may adversely affect outcome. The long-term nature symptoms suggestive of RA, regardless of a negative RF test result. of PMR, its associated disability and treatment with steroids means Disclosure statement: The authors have declared no conflicts of PMR patients may be at an increased risk of depression. The aim of interest. this study was to investigate the prevalence of depression in patients with PMR. Methods: All older adults aged 50 years registered with 150 general practices who had a first Read code for PMR in their medical records 049. MAKING IT EASY TO DO THE RIGHT THING: A PILOT TO in the preceding 3 years were mailed a questionnaire (n ¼ 704). Survey DEVELOP AN E-TEMPLATE TO ASSIST GPS IN MANAGING items included questions on patient demographics and PMR symp- PATIENTS WITH LOW BACK PAIN toms and duration. Depression was measured using the Patient Health Kay Stevenson1,2, Helen Duffy1, Simon Wathall1, Krysia Dziedzic1, Questionnaire 8 (PHQ-8), with current depression defined as a PHQ-8 Simon Somerville1,3, Vince Cooper1, Adrian Chudyk1,3, Sue Turner3, score of 10. Julie Oxtoby3 and Rhian Hughes1 Results: 550 patients responded (78%). The mean (S.D.) age was 74.2 1Arthritis Research UK Primary Care Centre, Keele University, (8.4) years and 365 (66%) were female. Non-responders did not differ Keele, 2Physiotherapy Department, University Hospital of North significantly from responders in terms of age (mean age 75 (9.2) vs Midlands, Stoke-on-Trent and 3Park Medical Centre, North 74.2 (S.D. 8.4), P ¼ 0.21) or gender (73% vs 66% females, P ¼ 0.14). Of Staffordshire Clinical Commissioning Group, Stoke-on-Trent, UK 489 patients with complete data, 79 (16.2%) patients were classified as having current depression, with the majority (41/79) having Background: Managing patients with low back pain with a stratified moderate depression. Depression was more common in women care approach (screening tool plus matched treatments) improves (44% vs 35%, although not statistically significant) and no clinical outcome and is cost effective. The STarT Back screening tool association between age and depression was seen. 336 (72%) still is a 9 item questionnaire that identifies patient’s risk (low, medium or had symptoms of PMR and those reporting current symptoms were high) of developing persistent disabling back pain. Matched treat- more likely to be depressed (65 (19.3%) with PMR symptoms had ments are provided as follows: general practitioner (GP) advice, current depression, vs 9 (6.9%) of those without PMR symptoms, analgesia and supported self-management for low risk patients, P ¼ 0.001). No relationship was seen between duration of PMR and traditional (manual) physiotherapy for medium risk patients and depression. psychologically informed physiotherapy for high risk patients. Conclusion: Depression is common in patients with PMR, especially However, this stratified approach is not being consistently embedded in patients with ongoing PMR symptoms. Clinicians should monitor into practice. Clinicians perceive back pain as being complex and that these patients for symptoms of depression and manage them computerized tools interfere with clinical decision making. The aim of appropriately as untreated depression may negatively impact on this innovation was to remove barriers to implementation and assist outcome. clinicians in their consultations with patients with low back pain. Disclosure statement: The authors have declared no conflicts of Methods: Five pilot GP practices were identified by a local clinical interest. Commissioning Group (CCG) as part of an Academic Health Science Network (AHSN) funded innovation. A dedicated implementation team 051. ALLOPURINOL USE AND THE ILLNESS PERCEPTIONS worked with GPs to design and test an IT solution which embedded OF GOUT PATIENTS IN PRIMARY CARE the screening tool for stratified care into the GP electronic system. The CCG identified quality indicators that could monitor activity along the Ciaran Walsh1, James Prior1, Priyanka Chandratre1 and care pathway, and could sustain and promote professional and system Edward Roddy1 level change. Use of the STarT Back tool, checking for red flags and 1Arthritis Research Primary Care Centre, Keele University, Keele, UK appropriate referral on to physiotherapy were measured. Small practice group meetings with GPs, practice nurses and practice Background: Gout is the most prevalent form of inflammatory arthritis, managers were used to discuss the original evidence and to refine the affecting 2.49% of UK adults. Gout is primarily managed in primary screening tool into an IT based solution that could be easily care and long-term treatment aims to lower serum uric acid levels incorporated into GP consultations. A dedicated IT system expert through the use of allopurinol. Individuals with chronic illnesses, such worked with the GPs and EMIS to design the appropriate e-template as gout, often conceptualize thoughts and emotions of their condition for testing. and related treatments into illness perceptions. Patients with negative Results: A dedicated protocol and e-template were co-created and illness perceptions have been shown to have poorer long-term health embedded within EMIS to support GPs during consultations. This outcomes, but such perceptions of gout patients, particularly about included an auto-calculated STarT Back score and a link to printable, using allopurinol, remain unclear. Our study examined the association bespoke patient information housed on patient.co.uk. Pop up advice between the use of allopurinol and the illness perceptions of gout for the GP was embedded dependent on the level of risk. An electronic patients from UK primary care. referral to physiotherapy services was automatically populated and Methods: As part of a longitudinal cohort study, a questionnaire was generated if required. As part of the pilot an email address was sent to 1805 adults with a primary care diagnosis of gout, 2 years prior established within physiotherapy services to allow a direct automatic to the questionnaire. This questionnaire asked participants to rate their referral. All of these options were contained within the existing clinical agreement with several statements from the brief illness perception system in primary care (EMIS). questionnaire: there is a lot I can do to control my gout; what I do will Conclusion: A computer template, bespoke patient information and affect my gout; treatments are effective; and gout is serious. automatic physiotherapy referral have been co-created by practi- Responder characteristics were described and logistic regression tioners to make it easier for them to deliver the best evidence base analysis used to establish any association between the use of care for patients with non-specific low back pain. Audit data on use of allopurinol and illness perceptions. Results were recorded as odds the tool and appropriate referral will be available to GPs, practices and ratios (95% CI) and adjusted for age, gender, deprivation, BMI, CCGs to explore use of the pathway. Following refinement the comorbidity, alcohol intake and gout-specific characteristics. POSTER VIEWING I Tuesday 28 April 2015 i69

Results: 1184 participants responded to the questionnaire (65.6%). positive early RA and confirm and extend previous observations Adjusted analysis showed no association between the use of allopurinol regarding anti-citrullinated and anti-carbamylated protein antibodies. and the perception of gout patients that there is a lot I can do to control Anti-CCP-positive RA patients displayed a distinct antibody profile my gout or what I do will affect my gout. However, gout patients using indicating that antibody production to these modified proteins is allopurinol were twice as likely to be uncertain [1.93 (1.2–3.0)] or disagree disease specific and not a generic response to inflammation. The [2.65 (1.4–5.1)] than agree that treatments are effective compared with presence of antibodies against acetylated lysine proteins in these those not using allopurinol. Finally, gout patients using allopurinol were patients may provide a link between the microbiome, self-antigen 50% more likely to be uncertain [1.55 (1.0–2.3)] than agree that gout is acetylation and autoimmunity in early RA. serious compared with those not using allopurinol. Disclosure statement: The authors have declared no conflicts of Conclusion: The use of allopurinol in UK primary care gout patients interest. was associated with negative or indifferent perceptions. As allopurinol is an effective urate-lowering therapy when used correctly, patients and general practitioners may benefit from better education about the 052 TABLE 1. Frequency of antibody seropositivity nature of gout, and the positive and negative effects associated with Antibody Anti-CCP Anti-CCP Persistent Resolving, % allopurinol. positive RA, % negative RA, % non-RA, % Disclosure statement: C.W. is funded by a Academy of Medical Anti-CitV 94 23 15 18 Sciences Inspire studentship. All other authors have declared no Anti-CarV 69 4 6 6 conflicts of interest. Anti-AcV 63 13 16 12.5 Anti-CCP 100 0 1.8 1.8 AcV: acetylated vimentin; CarV: carbamylated vimentin; CitV: citrullinated vimentin. RHEUMATOID ARTHRITIS: PATHOGENESIS 053. REASONS FOR TREATMENT DELAY IN EARLY RHEUMATOID ARTHRITIS DIFFER ACCORDING TO AUTOANTIBODY STATUS 052. PATIENTS WITH EARLY INFLAMMATORY ARTHRITIS Arthur G. Pratt1,2, Ben Hargreaves1,2, Christine Routledge2, WHO ARE ANTI-CCP ANTIBODY POSITIVE HAVE ANTIBODIES Lesley Tiffin2, Julie Norris2, Claire Humphrey2 and John D. Isaacs1,2 AGAINST ACETYLATED AND CARBAMYLATED VIMENTIN 1Institute of Cellular Medicine (Musculoskeletal Research Group), PEPTIDES Newcastle University and 2Musculoskeletal Directorate, Newcastle Maria Juarez1, Holger Bang2, Friederike Hammar2, Ulf Reimer3, upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK Bernard Dyke1, Christopher D. Buckley1, Benjamin Fisher1, Andrew Filer1 and Karim Raza1 Background: Evidence for a 12 week window of opportunity after 1Centre for Translational Inflammation Research, University of symptom onset, during which therapeutic intervention meaningfully Birmingham Research Laboratories., Birmingham, UK, 2ORGENTEC interrupts the natural history of RA, has led to a proliferation of early Diagnostika GmbH, ORGENTEC Diagnostika GmbH, Mainz and 3JPT arthritis clinics (EACs) intended to expedite diagnosis. However, patients continue to experience delays between symptom onset and Peptide Technologies GmbH, JPT Peptide Technologies GmbH, treatment initiation. Optimal interventions for improving access to Berlin, Germany DMARD therapy may differ between sub-groups of patients with RA. Methods: A single-centre retrospective analysis of a UK early RA Background: Serum autoantibodies are measured in RA patients for inception cohort was undertaken to identify those components of the diagnostic and prognostic purposes. Antibodies against citrullinated overall time-delay between symptom onset and treatment initiation peptides are directed against citrulline that results from post-transla- that differed according to patients’ autoantibody status. The primary tional modification (PTM) of arginine residues. Antibodies against time periods examined were symptom onset to Rheumatology referral, another PTM residue, homocitrulline, have recently been described in Rheumatology referral to EAC appointment and EAC appointment to RA patients’ sera. Lysine acetylation is another important PTM. Proteins DMARD initiation. For a subgroup of patients sufficient data was carrying this modification regulate metabolic pathways and host protein available to divide the first period into two parts: symptom onset to first acetylation is a mechanism through which the microbiome affects its general practitioner (GP) visit and first GP visit to Rheumatology host. Recent sequencing of the intestinal microbiome revealed a high referral. Detailed baseline characteristics were recorded, including prevalence of a specific bacterium, Prevotella copri, in patients with early serological status for RF and ACPAs. Time periods were dichotomized RA suggesting a pathogenic function. This function may be exerted and data were analysed using Pearson’s chi-squared test (with Wald’s through protein acetylation. To date there have been no studies of continuity correction for 2 2 contingencies), with a ¼ 5%. immunity against acetylated proteins in RA. Results: 166 RA patients were diagnosed over a 31 month period, of Objective: To investigate antibody reactivity against acetylated, whom 78 (47%) were ACPA/RF double seropositive, 54 (33%) double- citrullinated and homocitrullinated vimentin peptides in patients with seronegative, and 15 (9%) ACPA and 19 (11%) RF single seropositive, early inflammatory arthritis. respectively. Overall, the time between symptom onset and DMARD Methods: Microtitre plates were coated with vimentin derived initiation was similar between all serotypes (median 16 weeks). peptides identical in length and composition except at one amino Compared with their seropositive counterparts, double-seronegative acid that was changed to introduce a citrullinated, carbamylated or patients were more likely to experience delays between presentation in acetylated residue. By using a peptide of known sequence and secondary care and DMARD initiation (P < 0.05), whereas ACPA- introducing one modification at a time, we were able to determine positive patients were more likely to experience delays of >12 weeks specific antibody reactivities. Sera of 268 treatment naive patients with between symptom onset and referral from primary to secondary care early inflammatory arthritis and symptoms 3 month’s duration were (P < 0.05). Among a subgroup of 32 RA patients in whom data were tested. Patients were assigned to outcome categories at 18 month available, this delay in presentation of ACPA-positive patients to follow up. Anti-CCP antibody levels were determined using a secondary care was accounted for by a prolonged symptom duration commercial anti-CCP2 antibody assay (ELiAM). Sera of patients that prior to first consultation in primary care (P < 0.05) – and not by tested positive for antibodies against all modifications were preincu- delayed referral. bated sequentially with each of the modified peptides in competition Conclusion: Our exploratory analysis has identified the potential for experiments and antibody reactivities determined to investigate bottlenecks in the diagnosis and treatment of RA to differ in their binding specificity. contribution to treatment delays according to patients’ autoantibody Results: The frequency of antibody positivity is shown in Table 1. The status. In particular, our findings add credence to previous hints that proportion of patients with positive antibody tests was significantly seropositivity predicts a patient’s tendency to defer seeking medical higher in anti-CCP-positive RA (n ¼ 48) compared with anti-CCP- advice for joint pain. The observation warrants large-scale validation negative RA (n ¼ 53), persistent non-RA (n ¼ 55) and resolving arthritis and, if confirmed, awaits mechanistic explanation. Our findings also (n ¼ 112) groups for acetylated (P < 0.0001) citrullinated (P < 0.0001) highlight that the ongoing clinical challenge of diagnosing seronegative and carbamylated (P < 0.0001) peptides. No antibody reactivity was RA may account for delayed access to treatment in this group. An observed against the unmodified vimentin peptide in any group. improved understanding of these factors should inform the design of Competition experiments revealed negligible cross-reactivity between service delivery for early arthritis patients in the future. antibody populations. Disclosure statement: The authors have declared no conflicts of Conclusion: We show for the first time that antibodies against interest. acetylated vimentin are present in the sera of patients with anti-CCP- i70 Tuesday 28 April 2015 POSTER VIEWING I

054. THE IMPORTANCE OF IL-6-STAT3 MEDIATED measurements show promise as biomarkers of RA progression in ACTIVATION OF CIRCULATING CD4þ T CELLS IN THE seronegative UA. PATHOGENESIS OF EARLY SERONEGATIVE RHEUMATOID Disclosure statement: A.G.P. has received an unrestricted research ARTHRITIS: A VALIDATION STUDY grant from Pfizer. J.D.I. was co-recipient of an unrestricted research 1,2 1 3 grant from Pfizer. All other authors have declared no conflicts of Arthur G. Pratt , Amy E. Anderson , Nisha Nair , interest. Jonathan Massey3, Julie Diboll1, Andrew Skelton1, Ben Hargreaves1,2, Christine Routledge2, Dennis Lendrem1, Phil Brown1, Anne Barton3 and John D. Isaacs1,2 055. ARE SMOKING AND ALCOHOL ABSTINENCE RISK 1Musculoskeletal Research Group, Institute of Cellular Medicine, FACTORS FOR RHEUMATOID ARTHRITIS IN BLACK AFRICAN Newcastle University, 2Musculoskeletal Directorate, Newcastle upon AND BLACK CARIBBEAN ETHNICITY INDIVIDUALS? 3 Tyne Hospitals NHS Trust, Newcastle upon Tyne and Centre for 1 2 1 3 Ian C. Scott , Sophia Steer , Andrew P. Cope and Cathryn M. Lewis Musculoskeletal Research, Institute of Inflammation and Repair, 1Academic Rheumatology, King’s College London, 2Rheumatology, University of Manchester, Manchester, UK King’s College Hospital and 3Medical and Molecular Genetics, King’s College London, London, UK Background: Early diagnosis of RA improves outcomes but is challenging, particularly among ACPA-negative individuals. Previously Background: RA occurs when genetically predisposed individuals are we identified an IL-6-mediated CD4þ T cell transcriptional signature, exposed to environmental factors. The dominant RA environmental enriched for signal transduction and activation of transcription-3 risk factor in European populations is smoking. Drinking alcohol (STAT3) target genes, which had discriminatory value for this purpose. appears to protect against RA in Europeans. The relevance of these In the present work we sought independent replication of those risk factors to non-European populations is uncertain. We undertook a findings, the development of a more readily applicable diagnostic assay case–control study to evaluate the associations between smoking, and insight into mechanisms of disease induction. drinking and RA in Black African and Black Caribbean ethnicity Methods: Among 210 early arthritis patients attending the Newcastle individuals. Early Arthritis Clinic (NEAC) who were naive to immunomodulatory Methods: We evaluated 180 RA cases enrolled to the GENetics of RA treatment, serum cytokine levels were ascertained by immuno-assay. in individuals of African ancestry (GENRA) study. All met the 1987/2010 Constitutive and IL-6-induced expression of phosphorylated STAT1 ACR RA classification criteria and were of self-reported black African and 3 (pSTAT1/3) were determined in paired fresh circulating or black Caribbean ethnicity. Patients were recruited from South lymphocytes using flow cytometry. Finally, contemporaneous CD4þ London Rheumatology clinics. Smoking and alcohol intake data were T cell gene expression was measured in highly purified, fresh CD4þ T captured by interview. The study was ethically approved; all cells by hybridizing high-integrity RNA isolates to Illumina Human HT12 participants provided consent. Controls were evaluated from the BeadChips, and employing appropriate microarray normalization 2004 Health Survey for England (focussing on the health of Ethnic algorithms. Patients were followed up for >12 months and diagnostic minorities). 1812 controls of black African or black Caribbean ethnicity outcomes confirmed. Analyses included non-parametric ANOVA without a history of arthritis, rheumatism or fibrositis were included. (Dunn’s post-hoc group comparisons), Spearman’s rank correlation, Smoking and alcohol intake data were recorded as for cases. multiple regression and hierarchical clustering. Associations between smoking (ever vs. never), drinking (ever vs. Results: Consistent with previous observations, serum IL-6 levels never) and case-control status were examined by logistic regression, were significantly higher in early ACPA-negative RA patients (n ¼ 29) adjusting for age and gender (due to significant case-control than in inflammatory arthritis patients with alternative diagnoses differences in these characteristics). The effect of heavy smoking matched for acute phase response (n ¼ 59; P < 0.05). Constitutive (10 pack-years) on RA risk was assessed (referent to never-smokers/ pSTAT3, but not STAT1, correlated with serum IL-6 levels maximally in individuals reporting <10 pack-years). CD4þ T cells (P < 0.001) compared with CD8þ or CD19þ lymphocytes – Results: In black African individuals, smoking did not associate with and did so independently of CRP or other cytokines. Increased the risk of RA in African individuals (Table 1). Ever-smoking rates were constitutive pSTAT3, but not pSTAT1, was observed in circulating lower in cases (15.5%) than controls (22.9%). The adjusted odds ratio CD4þ T cells of early ACPA-negative RA patients compared with (OR) for RA in ever- vs. never-smokers was 1.05 (95% CI 0.48, 2.17). inflammatory disease controls (P < 0.01). Moreover, CD4þ T cell The risk of RA was not increased in heavy smokers. Restricting pSTAT3 correlated with the expression of each of the five STAT3- analyses to RF-positive cases revealed no association between inducible genes identified as part of our previously described 12-gene smoking and RA risk. Ever-drinking was not associated with RA risk early RA signature in this subset (E.g. SOCS3; P < 0.001). As before, (Table 1). In black Caribbean individuals, smoking associated with an hierarchical clustering based on the 12-gene signature convincingly increased risk of RA in Caribbean individuals (Table 1). Although ever- segregated RA from non-RA patients in the early arthritis setting. smoking rates were similar in cases (44.9%) and controls (46.4%), Finally, among 32 mainly ACPA-negative patients presenting with after adjusting for age and gender, ever-smoking associated with an undifferentiated arthritis (UA), the ratio of constitutive pSTAT3:pSTAT1 increased RA risk (OR 1.61, 95% CI 1.02, 2.57). Heavy smoking rates in CD4þ T cells could be incorporated into an algorithm for accurately were particularly higher in RF-positive cases (26.7%) compared with predicting progression to classifiable RA (area under the receiver controls (13.9%). A significantly increased risk of RF-positive RA was operating characteristic curve 0.87; P < 0.001). seen in heavy smokers (OR 2.20, 95% CI 1.16, 4.09). Ever-drinking Conclusion: Our findings validate those of our previous investigation. was not associated with RA risk in Caribbean individuals (Table 1). They support a particular role for IL-6-driven CD4þ T cell activation via Conclusion: Smoking is a risk factor for RA in black Caribbean STAT3 during the induction of RA, which is of particular importance in ethnicity individuals. This is particularly true of heavy-smoking and the pathogenesis of ACPA-negative disease. CD4þ T cell pSTAT RF-positive RA. Smoking does not appear to increase the risk of RA in

055 TABLE 1. Association between smoking, drinking and RA in black African and black Caribbean individuals Black African ethnicity

Smoking/drinking status All RA, n (%) (n ¼ 71) RF plus RA, n (%) (n ¼ 58) Controls, n (%) (n ¼ 837) Adjusted OR Adjusted OR (95% CI), (95% CI), all RA RF-positive RA Never-smoker 60 (84.5) 48 (82.8) 628 (77.1) — — Ever-smoker 11 (15.5) 10 (17.2) 186 (22.9) 1.05 (0.48, 2.17) 1.27 (0.55–2.72) >10 Pack-years 4 (5.7) 4 (7.0) 35 (4.6) 1.50 (0.40, 4.57) 2.10 (0.54–6.67) Never-drinker 33 (46.5) 27 (46.6) 305 (43.1) — — Ever-drinker 38 (53.5) 31 (53.4) 403 (56.9) 0.70 (0.40, 1.25) 0.70 (0.38–1.31)

Black Caribbean ethnicity

Smoking/drinking status All RA, n (%) (n ¼ 109) RF plus RA, n (%) (n ¼ 83) Controls, n (%) (n ¼ 975) Adjusted OR Adjusted OR (95% CI), (95% CI), all RA RF-positive RA

Never-smoker 59 (55.1) 45 (54.9) 508 (53.6) — — Ever-smoker 48 (44.9) 37 (45.1) 440 (46.4) 1.61 (1.02, 2.57) 1.67 (0.99–2.83) >10 Pack-years 22 (22.7) 20 (26.7) 120 (13.9) 1.72 (0.95–3.05) 2.20 (1.16–4.09) Never-drinker 22 (20.4) 20 (24.1) 108 (13.2) — — Ever-drinker 86 (79.6) 63 (75.9) 713 (86.8) 1.02 (0.57–1.87) 0.84 (0.46–1.61) OR: odds ratio. POSTER VIEWING I Tuesday 28 April 2015 i71

black African ethnicity individuals. Our findings suggest that environ- 057. ADHERENCE TO BIOLOGIC THERAPIES IN PATIENTS mental risk factors for RA differ between European and African WITH INFLAMMATORY ARTHRITIS populations. They also indicate that research into RA risk factors 1 2 2 needs undertaking separately in African and Caribbean ethnicity Elizabeth B. Brown , Susannah Earl , Richard Haigh and Ravik Mascarenhas2 individuals. 1 2 Disclosure statement: I.C.S. is supported by an Arthritis Research Peninsula Foundation School and Department of Rheumatology, UK Clinical Research Fellowship and an NIHR Clinical Lectureship. All Royal Devon & Exeter Hospital, Exeter, UK other authors have declared no conflicts of interest. Background: The World Health Organization estimates that <50% of patients with chronic diseases take their medications as prescribed. Optimal efficacy of biologic therapies is dependent upon adherence to the agreed treatment regime. A recent multicentre prospective RHEUMATOID ARTHRITIS: TREATMENT observational study showed that 27% of patients with RA starting a new s.c. biologic therapy were non-adherent to their treatment regime within the first 6 months, resulting in a lower DAS for 28 joints (DAS28) response. Local audit within our department has shown 20% of 056. PREDICTORS OF ORAL METHOTREXATE FAILURE IN patients on DMARDs are non-adherent to their treatment regime. Self- PATIENTS WITH EARLY INFLAMMATORY ARTHRITIS: A administration of s.c. biologic therapies brings the potential for COMPETING RISKS ANALYSIS wastage of costly medications. The purpose of this audit was to measure adherence to s.c. biologic therapies in patients with 1 1 2 James Bluett , Jamie Sergeant , Alex J. MacGregor , inflammatory arthritis and to estimate the associated cost of wastage 1 1 Deborah Symmons and Suzanne Verstappen of s.c. biologic therapies. 1 Arthritis Research UK Centre for Epidemiology, University of Methods: Medication adherence was measured using a survey sent 2 Manchester, Manchester and Norwich Medical School, University of by post to all of the patients known to our department with East Anglia, Norwich, UK inflammatory arthritis treated with a s.c. biologic therapy. The survey invited patients to indicate which therapy they were prescribed, how Background: MTX persistence is higher compared with other many doses of this medication they had missed over the preceding 6 DMARDs in patients with RA. The majority of patients with RA fail months and the reasons for the omission. MTX due to inefficacy or adverse events. Previous studies have Results: The completed surveys (n ¼ 119) demonstrate that 38% of identified factors associated with inefficacy and/or adverse events, but patients missed their biologic medication at least once in the the majority of these studies performed pre-2000 are inconsistent in preceding 6 months. The most commonly cited reasons for omitting their findings and do not control for competing risks. The aims of this doses of medication were infections (n ¼ 27) and forgetfulness (n ¼ 20). study were to (i) examine patient-reported reasons for stopping MTX in Excluding patients who missed medications due to infections, the patients with inflammatory polyarthritis and (ii) investigate which estimated wastage cost associated with missed medications over 6 factors predict MTX failure. months was £3660.24. Patients reported over-delivery of medications, Methods: Patients in this study were recruited to the Norfolk Arthritis resulting in an estimated wastage cost of £4818.21. Patients reported Register (NOAR), a primary care based inception cohort of patients wastage of out of date medications, returned medications and with early inflammatory polyarthritis. All patients recruited between disposed of medications resulting in an estimated wastage cost of 2000 and 2008 commencing oral MTX as their first DMARD within 3 £13 137. We estimate the total cost of wastage of biologic medications months of their baseline visit were eligible. Assessments included age, to be approximately £21 615 over 6 months. gender, smoking status, 28-swollen and tender joint count, visual Conclusion: This audit demonstrates significant non-adherence to analogue score and HAQ. Baseline blood is taken for measurement of biologic therapies by patients with inflammatory arthritis, which is CRP, shared epitope and RF. The DAS for 28 joints-CRP was known to be associated with poorer clinical outcomes. Patients calculated. Start and stop dates of any DMARD are recorded at appropriately follow advice to omit their biologic medication during each follow-up visit. Patient-reported reasons for stopping DMARDs intercurrent infections. Our analysis shows non-adherence is costly, are categorized into (i) adverse events, (ii) inefficacy, or (iii) other. and that savings could be made by appropriate intervention. To Adding a second DMARD was categorized as inefficacy. Patients were improve adherence, patients should be advised to set reminders for followed from recruitment until MTX failure because of inefficacy or when their medication is due. Further work could evaluate the use of adverse events up to 18 March 2013. Patients were censored if they technology, including smartphone reminder applications, in improving stopped MTX for other reasons or at last follow up in case of MTX adherence in this patient group. To reduce over-delivery, adminis- continuation. Predictors of MTX failure due to adverse events or trative staff could contact patients each time a prescription is inefficacy were identified using univariate Cox proportional hazards requested to establish how many syringes the patient has remaining regression. Variables with P < 0.2 and/or those previously shown to to ascertain an appropriate delivery quantity. Other departments predict MTX failure were included in the multivariate analysis. Failure employ a patient information leaflet to advise correct storage and due to adverse effects and inefficacy was treated as competing risks. promote patient-led supply management in order to reduce wastage, Results: 431 patients (63% women; median age 58) were included. which our department could utilize. Median baseline DAS for 28 joints (DAS28) was 3.8 (interquartile range Disclosure statement: The authors have declared no conflicts of 3.0–4.8). During 2035 person-years of follow up there were 67 MTX interest. failures due to adverse events (16%), 143 due to inefficacy (33%) and 35 for other reasons (8%). The probability of patients continuing MTX at 2 years was 0.75 (95% CI 0.71, 0.79). In the competing risks analysis RF 058. THE EFFICACY AND SAFETY OF SUBCUTANEOUS positivity was protective against adverse events (P < 0.001) and TOCILIZUMAB VERSUS INTRAVENOUS TOCILIZUMAB IN predictive of failure due to inefficacy (P ¼ 0.011; Table 1); older age at COMBINATION WITH TRADITIONAL DMARDS IN PATIENTS disease onset was protective against MTX inefficacy (P < 0.001) and WITH RA AT WEEK 97: RESULTS FROM THE SUMMACTA baseline DAS28-CRP was predictive of MTX inefficacy (P ¼ 0.008). STUDY Gender, symptom duration, smoking status, BMI, baseline HAQ and shared epitope status were not predictive of inefficacy or adverse Gerd Burmester1, Andrea Rubbert-Roth2, Alain Cantagrel3, events. Stephen Hall4, Piotr Leszczynski5, Daniel Feldman6, Madura Conclusion: Patients with inflammatory polyarthritis who are RF positive J. Rangaraj7, Georgia Roane8, Charles Ludivico9, Eduardo Mysler10, and have a higher baseline DAS28-CRP are at increased risk of MTX Melanie J. Bennett11, Lucy Rowell11 and Min Bao12 failure due to inefficacy. This cohort may therefore require earlier 1Charite´ -Universita¨ tsmedizin Berlin, Free University and Humboldt combination DMARD therapy in order to control disease activity. University of Berlin, Berlin, 2Medical Department, Klinikum der Disclosure statement: The authors have declared no conflicts of Universita¨ tzuKo¨ ln, Ko¨ ln, Germany, 3Rhumatologie, Centre interest. Hospitalier Universitaire de Toulouse, Toulouse, France,

056 TABLE 1. Predictors of MTX failure: competing risk analysis Predictive factor Adverse event, P-value Interpretation Inefficacy, P-value Interpretation coefficient (95% CI) coefficient (95% CI) RF positivity 1.08 (1.63, 0.53) <0.001 Protective 0.51 (0.12, 0.91) 0.011 Harmful Age at symptom onset 0.24 (0.15, 0.63) 0.222 No association 0.03 (0.04, 0.01) <0.001 Protective DAS28-CRP 0.00 (0.01, 0.02) 0.672 No association 0.21 (0.05, 0.36) 0.008 Harmful DAS28: DAS for 28 joints. i72 Tuesday 28 April 2015 POSTER VIEWING I

4Rheumatology Department, Cabrini Medical Centre, Malvern, A.C. has acted as a consultant for BMS, Chugai, Roche, UCB, Abbott Australia, 5Medical Department, Poznan Medical University, Poznan, and Pfizer; and has received research grants from UCB and Pfizer. P.L. Poland, 6Medical Department, Universidade Federal de Sa˜ o Paulo, has acted as a consultant for Roche. M.J.R. has received research Sa˜ o Paulo, Brazil, 7Arthritis & Diabetes Clinic, Inc, Monroe, Los funding from Roche. C.L. has served on speakers’ bureaus on behalf Angeles, CA, 8Rheumatology, Rheumatology Associates of South of BMS; and has received research grants from Roche, BMS, Pfizer, Carolina, Charleston, SC, 9Rheumatology, East Penn Rheumatology Human Genome Science, Lilly and Sanofi-Aventis. E.M. has acted as a Associates, Bethlehem, PA, USA, 10Reumato´ logo, Organizacion consultant for Roche; has served on speakers’ bureaus on behalf of Medica de Investigacio´ n, Buenos Aires, Argentina, 11Medical Roche; and has received research funding from Roche. M.J.B. is an Department, Roche Products Ltd, Welwyn Garden City, UK and employee of Roche. L.R. is an employee of Roche. M.B. is an 12Medical Department, Genentech, South San Francisco, CA, USA employee of Genentech. All other authors have declared no conflicts of interest. Background: Tocilizumab (TCZ) is approved as an i.v. formulation globally, and as a s.c. formulation in the USA and Europe, for the treatment of adult RA. In the SUMMACTA study, efficacy and safety of 059. RISK OF SKIN CANCER FOLLOWING ANTI-TUMOUR s.c. TCZ weekly (qw) was demonstrated through week 24 and week 49 NECROSIS FACTOR TREATMENT IN RHEUMATOID AND in patients (pts) with RA with an inadequate response to DMARDs. Our PSORIATIC ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW objectives were to evaluate the efficacy and safety of TCZ-s.c. vs TCZ- i.v., including in pts who switched from TCZ-i.v. to s.c. TCZ and vice Rhea Chatterjea1, Maeve Mc Laughlin2, Isla L. Kuhn3 and versa, through week 97. Andrew O¨ sto¨ r2 Methods: SUMMACTA is a 2-year, randomized phase 3 study. Pts 1School of Clinical Medicine, University of Cambridge, (n ¼ 1262) were randomized (blinded) 1:1 to receive s.c. TCZ 162 mg 2Rheumatology Clinical Trials Unit, Addenbrooke’s Hospital, qw (n ¼ 631) or i.v. TCZ 8 mg/kg every 4 weeks (q4w; n ¼ 631) in Cambridge University Hospitals NHS Foundation Trust and combination with traditional DMARDs. After 24 weeks, pts who initially 3University Library – Medical Library, University of Cambridge, received s.c. TCZ were re-randomized (open-label) 11:1 to s.c. TCZ Cambridge, UK qw (n ¼ 521) or i.v. TCZ q4w (n ¼ 48) and pts who initially received i.v. TCZ were re-randomized 2:1 to i.v. TCZ q4w (n ¼ 372) or TCZ-s.c. qw Background: Anti-tumour necrosis factor (anti-TNF) therapy has been (n ¼ 186). widely used for refractory RA and PsA over the past 10 years. Safety Results: A total of 76 (14.6%), 61 (16.4%), 8 (16.7%) and 26 (14.0%) data from randomized controlled trials (RCTs) and cohort studies have patients from the s.c. TCZ, - i.v. TCZ, s.c. TCZ to i.v. TCZ and i.v. TCZ identified a potentially increased risk of malignancy, particularly skin to s.c. TCZ groups, respectively, withdrew from the study through cancers. Our objective was to investigate the risk of skin cancer week 97. The percentages of pts who achieved ACR20/50/70 following anti-TNF therapy in RA and PsA patients. responses, DAS for 28 joints remission and an improvement from Methods: We conducted a systematic literature review using the baseline in HAQ-DI 0.3 were sustained through week 97 (Table 1) and Cochrane Library, EMBASE, PubMed and Web of Science databases. comparable across treatment groups. The safety profiles of switchers Only human RCTs and cohort studies published in English were were similar to pts with continuous s.c. TCZ or i.v. TCZ treatment analysed. Data extracted for comparison included study population (Table 1). No anaphylaxis cases were identified. The proportions of pts characteristics, prior exposures, confounding factors, interventions, who developed anti-TCZ antibodies remained low and were compar- number and type of malignancies (specifically melanomas, basal cell able across treatment groups through week 97. No association and squamous cell carcinomas). Risk of study bias was assessed between anti-TCZ antibody development and clinical response or based on the Cochrane Risk of Bias Assessment Tool. AEs was observed. Results: The search yielded 282 results, 15 of which met the inclusion Conclusion: The long-term efficacy and safety of s.c. TCZ qw is criteria. We analysed 5 RCTs and 10 cohort studies, covering a total of maintained and remains comparable to i.v. TCZ, with the exception of 358 734 patients. Of the 12 studies collecting data for non-melanoma injection site reactions. The efficacy and safety profiles of pts who skin cancers (NMSCs) in RA patients treated with anti-TNFs, three switched were comparable to those for pts who remained on i.v. TCZ reported significant odds or hazard ratios (Table 1). There was an or s.c. TCZ. S.c. TCZ could provide a more convenient administration increased risk of NMSCs [hazard ratio (HR): 1.42 (1.23–1.65)] with option in pts with RA. anti-TNF treatment in a population of 19 200 American veterans Disclosure statement: G.B. has acted as a consultant for Roche, (90.7% male) as well as in a large observational study involving 13 001 Chugai, Pfizer, UCB and BMS; has served on speakers’ bureaus on patients [odds ratio: 1.5 (1.2–1.8)]). The risk of NMSCs was increased behalf of Roche, Pfizer, MSD, BMS and Abbott; and has received in 1 study when anti-TNF was combined with MTX [HR 1.97 (1.51– research grants from Roche, Abbott, Pfizer, UCB, BMS and MSD. 2.58)] compared with anti-TNF without MTX [HR 1.24 (0.97–1.58)]. A.R.-R. has acted as a consultant for Roche, Chugai, Pfizer, MSD, There was no increased risk of melanomas documented in RA patients Abbott and UCB; has served on speakers’ bureaus on behalf of Roche treated with anti-TNFs. There was insufficient data to comment on PsA and UCB; and has received research grants from Roche and Pfizer. cohorts.

058 TABLE 1. Efficacy and safety data from SUMMACTA S.c. TCZ qw, S.c. TCZ qw, I.v. TCZ q4w, TCZ- i.v. q4w, TCZ-s.c.! i.v., TCZ- i.v.! s.c., week 24 week 97 week 24 week 97 week 97 week 97 Efficacy (ITT populationa,b) n/N % n/N % n/N % n/N % n/N % n/N % ACR20 391/518 75.5 377/451 83.6 291/372 78.2 264/317 83.3 33/40 82.5 146/165 88.5 ACR50 263/518 50.8 295/451 65.4 196/372 52.7 198/317 62.5 23/40 57.5 111/165 67.3 ACR70 143/518 27.6 202/451 44.8 114/372 30.6 133/317 42.0 15/40 37.5 78/165 47.3 DAS28 <2.6 198/517 38.3 238/446 53.4 137/370 37.0 142/306 46.4 20/40 50.0 90/162 55.6 # in HAQ-DI 0.3 347/516 67.2 322/445 72.4 254/371 68.5 219/317 69.1 22/39 56.4 115/162 71.0 Safety (safety population): rate/100 patient-years (95% CI) [no. events] n 631 631c 631 631c 48d 186d Adverse events 602.8 (574.9, 631.7) 415.9 (403.4, 428.6) 588.4 (560.8, 617.1) 408.6 (394.8, 422.7) 271.9 (233.7, 394.9 (370.9, 420.1) [1747] [4214] [1697] [3336] 314.7) [180] [1010] Serious adverse events 11.7 (8.1, 16.4) [34] 14.6 (12.4, 17.2) [148] 14.9 (10.8, 20.1) [43] 15.4 (12.9, 18.4) [126] 9.1 (3.3, 19.7) [6] 19.6 (14.5, 25.8) [50] Infections 120.1 (107.8, 133.4) 108.7 (102.3, 115.3) 124.8 (112.3, 138.4) 105.6 (98.6, 112.9) 84.6 (63.9, 109.9) 97.0 (85.3, 109.8) [348] [1101] [360] [862] [56] [248] Serious infections 3.1 (1.4, 5.9) [9] 4.0 (2.8, 5.4) [40] 3.5 (1.7, 6.4) [10] 3.9 (2.7, 5.5) [32] 1.5 (0.04, 8.4) [1] 6.7 (3.9, 10.6) [17] ISRs 58.0 (49.5, 67.4) 26.1 (23.0, 29.4) 32.6 (26.3, 39.9) —e —e 93.5 (82.0, 106.1) [168] [264] [94] [239] Serious hypersensitivity 0.7 (0.1, 2.5) [2] 0.5 (0.2, 1.2) [5] 1.0 (0.2, 3.0) [3] 0.2 (0.03, 0.9) [2] 0 [0] 0 [0] eventsf Deaths 0 [0] 0.4 (0.1, 1.0) [4] 0.4 (0.01, 1.9) [1] 0.5 (0.1, 1.3) [4] 0 [0] 0.8 (0.1, 2.8) [2] aThe week 24 ITT population comprised all patients who received a dose of TCZ, and groups are presented according to the treatment randomized at baseline. The week 97 ITT population comprised all patients who received a dose of TCZ post week 24 and groups include patients who were re-randomized to the same treatment assigned at baseline. bThe per-protocol population is the primary efficacy analysis for week 24. cIncludes all patients who received at least one dose of s.c. TCZ or i.v. TCZ from baseline to week 97. Safety data are cumulative through week 97. dPatients in the switch groups were re-baselined to the visit of their first open-label dose. eISR data were not collected in the i.v. TCZ group after week 24 as no s.c. injections were given. fSerious adverse events occurring during or within 24 h of the injection/infusion, excluding ISRs, and that were not deemed to be unrelated to treatment by the investigator. DAS28: DAS for 28 joints; ISR: injection site reaction; ITT: intent-to-treat. POSTER VIEWING I Tuesday 28 April 2015 i73

059 TABLE 1. Non-melanoma skin cancers in RA patients Study Biologic agent Treatment group Control group OR SIR

Patients, n NMSCs, n BCCs, n SCCs, n Patients, n NMSCs, n BCCs, n SCCs, n HR 1 Adalimumab, 19 750 134 ND ND 9805 77 ND ND 1.07 (0.79–1.46) ND ND etanercept, infliximab 2 Adalimumab, 3347 42 ND ND 3812 34 ND ND 1.10 (0.69–1.76) ND ND etanercept, infliximab 3 Adalimumab, 6282 297 ND ND 6634 326 ND ND ND 1.5 (1.2– ND etanercept, 1.8) infliximab, anakinra 4 Etanercept 126 442 29 NA 29 NA NAa NA NA NA NA ND 5 Adalimumab, 4088 283 ND ND 18 396 1043 ND ND 1.42 (1.23–1.65) ND ND etanercept, infliximab 6 Adalimumab, 4160 11 NA 11 56 770 379 NA 379 ND ND 3.6 (1.8–6.5)b etanercept, infliximab 7 Adalimumab, ND ND ND ND ND ND ND ND Anti-TNF only 1.24 ND ND etanercept, (0.97–1.58); anti-TNFþ infliximab MTX 1.97 (1.51–2.58) 8 Adalimumab, 11 881 395 342 53 3629 450 407 43 BCCs 0.95 (0.53–1.71), ND 1.72 (1.43– etanercept, SCCs 1.16 (0.35-3.84) 2.04)c infliximab 9 Adalimumab 553 45 ND ND 200 ND ND ND ND ND ND 10 Golimumab 276 9 ND ND 116 2 ND ND ND ND ND 11 Certolizumab 960 4 4 NA NA NA NA NA NA NA NA 12 Adalimumab 542 45 ND ND 257 ND ND ND NA NA SCCs 2.69 (1.23–5.11), NMSCs 1.74 (1.21–2.42) aExpected rates of SCC in the general population for an equivalent cohort size would be 849.1 in Arizona and 372.9 in Minnesota according to the rates documented. bCompared with the general Swedish population rates. cCompared with the general UK population; the SIR for patients not treated with anti-TNFs compared with the UK population was 1.83 (1.30–2.50). BCC: basal cell carcinoma; SCC: squamous cell carcinoma; NMSC: non-melanoma skin cancer; SIR: Standardized Incidence Ratio; NA: not applicable, ND: not documented.

Conclusion: We did not find an increased risk of melanomas with anti- structural joint damage in patients with early RA in AVERT, MRI TNF therapy in RA patients. There may however be an increased risk of changes were evaluated after 12 months on treatment and following NMSCs in anti-TNF-treated RA patients, particularly in males and the withdrawal of all RA medication in patients in DAS-defined those taking concomitant MTX. This risk should be considered when remission or low disease activity. commencing anti-TNF therapy. Further investigation is required to Methods: Patients with a DAS28-CRP of 3.2 mg/dl, onset of determine a relationship between skin cancers and anti-TNF therapy in symptoms 2 years and active synovitis in 2 joints, who were MTX PsA patients. naive and anti-CCP antibody (CCP2) positive were randomized to s.c. Disclosure statement: A.O¨ . acts as a consultant for Roche, Lilly, ABA 125 mg/week plus MTX, s.c.ABA 125 mg/week monotherapy or Chugai, MSD, AbbVie, Pfizer, Novartis, Napp and BMS; and has MTX alone for 12 months. All RA treatment was removed after 12 received research support from (including attendance at conferences) months (ABA immediately and MTX and steroids tapered over 1 and undertakes clinical trials for Roche, Lilly, Chugai, MSD, AbbVie, month) in patients with DAS28-CRP <3.2 mg/dl. Gadolinium-enhanced Pfizer, Novartis, Napp and BMS. All other authors have declared no MRI of the clinically worse hand/wrist was performed at baseline and conflicts of interest. at months 6, 12, 18 and 24. Adjusted mean changes from baseline in synovitis, osteitis and erosion were calculated at months 12 and 18 for patients with MRI assessments. In a post-hoc analysis, adjusted mean 060. SUSTAINED IMPROVEMENTS IN MAGNETIC changes from baseline in synovitis, osteitis and erosion MRI scores RESONANCE IMAGING OUTCOMES WITH ABATACEPT were compared in patients who had DAS28-CRP <2.6 mg/dl at both FOLLOWING THE WITHDRAWAL OF ALL TREATMENT IN months 12 and 18 (after withdrawal). PATIENTS WITH EARLY RHEUMATOID ARTHRITIS Results: Patients in the intent-to-treat population had early RA (mean

1 2 3 symptom duration 0.56 years) with highly inflammatory disease (mean Charles Peterfy , Gerd R. Burmester , Vivian P. Bykerk , Bernard tender joint count 23.3, swollen feet joint count 16.5, CRP 17.5 mg/dl), G. Combe4, Julie C. DiCarlo5, Daniel E. Furst6, Tom W. J. Huizinga7, 8 8 9 severe disease activity (mean DAS28-CRP 5.44 mg/dl and HAQ-DI Chetan S. Karyekar , Dennis A. Wong , Philip Conaghan and 1.42), poor prognostic factors (95.2% RF and anti-CCP2 double Paul Emery9 1 2 positive) and 31.9% were on steroids at baseline (mean dose 7.0 mg/ Radiology, Spire Sciences, Inc., Boca Raton, FL, USA, Department day). Improvements in synovitis and osteitis were greater and the of Rheumatology and Clinical Immunology, Charite´ – University progression of erosion was less in the ABA plus MTX arm versus MTX, 3 Medicine Berlin, Berlin, Germany, Department of Rheumatology, both on treatment (month 12) and following all treatment withdrawal Hospital for Special Surgery, Weill Cornell Medical College, New (month 18); benefits of ABA monotherapy on synovitis at months 12 4 York, NY, USA, Service d’Immuno-Rheumatologie, Montpellier and 18 and osteitis at month 12 were intermediate to those of ABA 5 University Hospital, Montpellier, France, Department of Imaging and plus MTX and MTX alone (Table 1). In patients with DAS28-CRP Data Science, Spire Sciences, Inc., Boca Raton, FL, 6Department of <2.6 mg/dl at both months 12 and 18, MRI benefits were maintained Medicine, University of California Los Angeles, Los Angeles, CA, from month 12 to month 18 (Table 1). USA, 7Department of Rheumatology, Leiden University Medical Conclusion: Abatacept reduced MRI-detected joint inflammation and Centre, Leiden, The Netherlands, 8Global Clinical Research, Bristol- joint damage in patients with early RA; these benefits may be Myers Squibb, Princeton, NJ, USA and 9Leeds Institute of Rheumatic maintained for at least 6 months after treatment withdrawal in patients and Musculoskeletal Medicine, University of Leeds, Leeds, UK who are in remission or low disease activity, suggesting an alteration in the autoimmune process. Background: Biologic treatment can lead to improved clinical Funding statement: This study was supported by Bristol-Myers outcomes in early RA. In the Assessing Very Early Rheumatoid Squibb. Arthritis Treatment (AVERT) study, abatacept (ABA) plus MTX achieved Disclosure statement: C.P. has received consulting fees from significantly higher rates of DAS for 28 joints (DAS28)-defined AbbVie, Amgen, AstraZeneca, BMS, Centocor, Five Prime remission (DAS28-CRP <2.6 mg/dl) versus MTX alone at 12 months Therapeutics, Genentech, Janssen, Lilly USA, Medimmune, Merck of treatment; a small but significantly higher number of patients on Pharmaceuticals, Novartis Pharmaceuticals, Roche and UCB; is a ABA plus MTX versus MTX alone sustained remission following the shareholder of Spire Sciences; and has served on speakers’ bureaus rapid withdrawal of all RA drugs. To assess the progression of on behalf of Amgen. G.R.B. has received consulting fees from AbbVie, i74 Tuesday 28 April 2015 POSTER VIEWING I

060 TABLE 1. Adjusted mean change from baseline in MRI scores ABA plus MTX ABA monotherapy MTX Intent-to-treat population, n 119 116 116 Synovitis Month 12 2.35 (2.89, 1.81)*, n ¼ 91 1.36 (1.91, 0.80), n ¼ 81 0.68 (1.24, 0.13), n ¼ 84 Month 18 1.34 (2.18, 0.50), n ¼ 38 1.19 (2.01, 0.31), n ¼ 35 0.49 (1.45, 0.46), n ¼ 29 Osteitis Month 12 2.58 (3.47, 1.69)*, n ¼ 91 1.37 (2.27, 0.46), n ¼ 81 0.68 (1.59, 0.24), n ¼ 84 Month 18 2.03 (3.72, 0.34), n ¼ 38 0.45 (1.31, 2.20), n ¼ 35 0.34 (1.55, 2.24), n ¼ 29 Erosion Month 12 0.19 (0.46, 0.84)*, n ¼ 91 1.42 (0.76, 2.07), n ¼ 81 1.53 (0.86, 2.19), n ¼ 84 Month 18 0.13 (0.74, 1.01)*, n ¼ 38 1.85 (0.96, 2.74), n ¼ 35 2.00 (1.07, 2.93), n ¼ 29 Post-hoc analysis in patients 18 14 9 with DAS28-CRPa, n Synovitis Month 12 1.95 (2.82, 1.08), n ¼ 18 2.43 (3.38, 1.48), n ¼ 12 1.25 (2.62, 0.13), n ¼ 6 Month 18 2.14 (3.14, 1.15), n ¼ 16 2.45 (3.49, 1.41), n ¼ 13 1.47 (2.85, 0.10), n ¼ 8 Osteitis Month 12 2.39 (3.15, 1.63), n ¼ 18 2.06 (2.86, 1.26), n ¼ 12 1.28 (2.39, 0.16), n ¼ 6 Month 18 2.37 (3.10, 1.63), n ¼ 16 2.23 (2.98, 1.49), n ¼ 13 1.46 (2.48, 0.43), n ¼ 8 Erosion Month 12 0.18 (0.79, 1.15), n ¼ 18 0.42 (0.57, 1.42), n ¼ 12 1.21 (0.16, 2.58), n ¼ 6 Month 18 0.09 (0.93, 1.12), n ¼ 16 0.36 (0.70, 1.41), n ¼ 13 1.25 (0.18, 2.68), n ¼ 8 *P < 0.05 for treatment difference vs MTX (95% CI) for the estimate of treatment difference did not cross 0). aThere were no significant treatment differences vs MTX. DAS28: DAS for 28 joints.

BMS, MSD, Medimmune, Novartis, Pfizer, Roche, Sandoz and UCB; 59 (54–63) years. 16 RA (2.8% of all RA patients in this cohort), 1 SLE, has served on speakers’ bureaus on behalf of AbbVie, Roche, BMS, 1 cryoglobulinemia and 1 SS. All except the SLE patient received Sandoz, MSD, UCB, Pfizer; and has received research grants from concomitant MTX. Neutropaenia occurred at median 15 weeks (range AbbVie, Pfizer, Roche and UCB. V.P.B. has received research grants 4–25) following rituximab infusion and median 2nd cycle (range 1–5). from Amgen, Pfizer, BMS, Janssen, UCB and Roche/Genentech. The majority of neutropenic episodes were transient; neutrophil count B.G.C. has served on speakers’ bureaus on behalf of BMS, Merck, was normal on the first repeat test in 12 (63%) patients. The frequency Pfizer, Roche-Chugai, UCB; and has received research grants from of mild (>1.0 09/l), moderate (0.5–1.0 109/l) and severe Pfizer and Roche-Chugai. J.C.D. is an employee of Spire Sciences. (<0.5 109/l) neutropaenia were 6(0.8%), 4(0.5%) and 9(1%) patients D.E.F. has received consulting fees from AbbVie, Actelion, Amgen, respectively. Of these, 7 infections requiring antibiotics were recorded BMS, Cytori, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/ in severe neutropenia cases, most commonly chest infection [five also Genentech and UCB; has served on speakers’ bureaus on behalf of required granulocyte-colony stimulating factor (GCSF)]. No case of AbbVie, Actelion, UCB; and has received research grants from AbbVie, neutropaenia >0.5 109/l was associated with infection. Irrespective Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/ of the degree of neutropaenia, all patients responded to rituximab and Genentech and UCB. T.W.J.H. has received consulting fees from 70% of them had complete B cell depletion as assessed by highly Abbott Laboratories, Biotest AG, BMS, Crescendo Bioscience, sensitive FACS. 18 patients were retreated with rituximab 2 1000 mg: Novartis Pharmaceuticals, Pfizer, Roche, Sanofi-Aventis, Schering- 9 had no recurrence of neutropaenia, 6 mild neutropaenia in next cycle Plough, UCB and Eli Lilly; has served on speakers’ bureaus on behalf and 3 in later cycles, without associated infection or requirement for of Abbott Laboratories, Biotest AG, BMS, Novartis Pharmaceuticals GCSF. Corporation, Pfizer, Roche, Sanofi-Aventis, Schering-Plough; has Conclusion: This is the largest cohort analysed for rituximab- received research grants from the EU and the Dutch Arthritis associated neutropaenia. It can be concluded that at <3%, it is less Foundation; and has non-remunerative positions of influence such as common in rheumatic disease than lymphoma; monitoring alone is officer, board member, trustee or public spokesperson for Meteor appropriate unless there is evidence of infection, when GCSF may be Board, Abbott Laboratories and Roche. C.S.K. is an employee of BMS. required; the majority of the neutropenia cases recovered promptly; D.A.W. is an employee and shareholder of BMS. P.C. has served on counts >0.5 109/l had no infections; on retreatment, mild neutro- speakers’ bureaus on behalf of AbbVie, AstraZeneca, Bioiberica, BMS, paenia recurred in only half with few consequences, with no evidence Centocor, Janssen, Merck Pharmaceuticals, Novartis, Pfizer, Roche for neutropaenia becoming more severe on repeat cycles; and it and UCB; has received research grants from Centocor Research & therefore appears retreatment with monitoring is appropriate with Development and Pfizer. P.E. has received consulting fees from caution only in severely neutropenic patients. The aetiology of AbbVie, BMS, Merck, Pfizer, Roche and Takeda; and has received rituximab-associated neutropaenia needs further investigation. research grants from AbbVie, BMS, Merck, Pfizer and Roche. Disclosure statement: J.C.F.F. has received honoraria from Roche; and has received research funding from the Sociedade Portuguesa de Reumatologia and MSD. Md.Y.Md.Y. has received research grants 061. RITUXIMAB-ASSOCIATED NEUTROPAENIA: SAFETY from the NIHR. E.M.V. has received honoraria and research grant OF RETREATMENT RITUXIMAB THERAPY support from Roche and GSK. P.E. has received consultant fees from BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB; and has 1,2 1,3 1,3 Joana C. F. Ferreira , Md Yuzaiful Md Yusof , Sudipto Das , received research grants paid to his employer from Abbott, BMS, 1,3 1,3 Edward M. Vital and Paul Emery Pfizer, MSD and Roche. The other author has declared no conflicts of 1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, interest. University of Leeds, Leeds, UK, 2Rheumatology Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universita´ rio de 3 Coimbra, Coimbra, Portugal and NIHR Leeds Musculoskeletal 062. OPTIMIZING TREATMENT WITH TNF INHIBITORS IN Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, RHEUMATOID ARTHRITIS: IS DOSE TAPERING PRACTICAL IN Leeds, UK OPTIMAL RESPONDERS? THE OPTTIRA TRIAL

1 1 1 Background: Neutropaenia is reported as a complication of rituximab James Galloway , Gabrielle Kingsley , Margaret Ma , 1 2 3 therapy for B cell malignancies with an incidence of 3–27%. As data in Beatriz Lorente-Canovas , David Walker , Ira Pande , 1 4 5 1 rheumatic diseases are more limited, the optimal management of Andrew Cope , David G Scott , Caroline J. Dore´ , Fowzia Ibrahim 1 these patients has not been defined. The aims of this study were to and David L Scott 1 determine the incidence of rituximab-associated neutropaenia, rates Academic Departmen of Rheumatology, King’s College School of 2 of infection; time for recovery; and safety of retreatment with rituximab Medicine, King’s College London, London, Musculoskeletal as a basis for management guidelines. Research Unit, Freeman Hospital, Newcastle University, Newcastle Methods: We conducted an observational study on all patients treated Upon Tyne, 3Department of Rheumatology, Queen’s Medical Centre, with rituximab in a single centre between 2003 and 2014. Each cycle Nottingham University, Nottingham, 4Rheumatology, Norfolk and consisted of 2 1000 mg (with a small percentage receiving half dose Norwich University Hospital, Norwich and 5Clinical Trials Unit, if in remission), repeated either on clinical relapse or pre-emptively. University College London, London, UK Rituximab-associated neutropaenia was defined as an absolute neutrophil count <2.0 109/l occurring at least 4 weeks after rituximab Background: Treating established RA with tumour necrosis factor excluding chronic neutropaenia or alternative plausible explanation inhibitors (TNFis) following NICE guidelines involves inducing then (e.g. Felty’s syndrome). maintaining responses. Currently both use identical TNFi-dosing Results: Rituximab-associated neutropaenia was identified in 19 regimens. OPTTIRA, a pragmatic, multicentre, 12-month randomized patients (2.5%) from a cohort of 753 and in 33 (1.1%) out of 3068 controlled trial, evaluated whether tapering TNFi doses causes loss of cycles of treatment. 16 were female; median (interquartile range age response. POSTER VIEWING I Tuesday 28 April 2015 i75

Methods: We recruited RA patients receiving etanercept or adalimu- concepts from health psychology such as illness perceptions and mab plus a DMARD with stable low disease activity [DAS for 28 joints psycho-education regarding problem domains in RA, e.g. pain, fatigue (DAS28) less than 3.2 for over 3 months]. We excluded patients with and medication adherence. After completion of the training, contin- serious concomitant illness or taking high-dose steroids (more than uous supervision and support is available to rheumatology practi- 10 mg prednisolone daily). Initially (months 0–6) patients were tioners in the form of email and telephone communication and an randomized to three groups: controls received constant TNFis; one online forum where questions and experiences can be discussed. experimental group tapered TNFis by 33% and the other by 66%. If Sessions are audio-recorded and rated by two independent assessors tapering caused flares (increase in DAS28 more than or equal to 0.6 using predefined criteria. Live feedback on performance is provided to plus 1 or more swollen joints out of 66 joints) TNFis were restarted. practitioners. Subsequently (months 6–12) controls tapered TNFis and experimental Results: 35 rheumatology practitioners from different hospital trusts groups discontinued TNFis. The outcomes comprised flare rates and throughout the UK attended the training between February and DAS28 scores after 6 months constant or tapered TNFis. November 2014. An additional 20 will be trained by March 2015. The Results: 227 patients were screened at 20 UK centres, 103 were intervention is currently being delivered at one site and scheduled to randomized, 97 were treated in months 0–6 and 74 in months 6–12. commence at all sites in due course. Preliminary data indicate most of With TNFis tapering: flares occurred in 14% of controls, 13% patients the skills delivered in the training were used effectively by the tapered by one-third and 37% tapered by two-thirds. Flares were practitioner and elicited positive responses from patients. More data increased with two-thirds tapering with odds ratio 4.1; 95% (CI 1.3, will be available as implementation of the intervention will continue in 14.5) compared with one-third tapering. Post-tapering flares resolved TITRATE. when TNFis were restarted. Mean DAS28 scores were similar after 6 Conclusion: Provision of MI-based psychosocial support in consulta- months standard TNFis doses and with both tapering strategies tions appears to be feasible for rheumatology practitioners with a (Table 1). With stopping TNFis 47 patients tapered then stopped positive response from patients. Additional data will provide evidence TNFis. 21/47 (45%) succeeded without flaring and their final mean whether this intervention can significantly contribute to enhancing DAS28 scores after stopping treatment were 2.2 (95% CI 1.6, 2.9). remission rates and QoL in patients with intermediate RA. Evaluating harms showed one patient withdrew for TNFis-related Funding: This work was funded by an unrestricted educational bursary toxicity (control) and four patients had serious adverse events (control from NIHR. 1; experimental 3); none were related to TNFis tapering. Disclosure statement: The authors have declared no conflicts of Conclusion: Good responses to TNFi are maintained after TNFi doses interest. are tapered by one-third. Tapering by two-thirds results in more flares, which respond to restarting TNFis. Some patients maintain responses 064. THE SOCIAL CARE EXPERIENCES OF PEOPLE WITH after stopping TNFis. Lowering TNFi maintenance doses retains RHEUMATOID ARTHRITIS responses at substantially reduced NHS costs. Adopting this strategy should enhance biologic cost-effectiveness. Jamie Hewitt1, Laura Wetherly1 and Benjamin Clubbs Coldron1 Disclosure statement: The authors have declared no conflicts of 1Government Affairs, National Rheumatoid Arthritis Society, interest. Maidenhead, UK

Background: Little research has been conducted into the social care 062 TABLE 1. Main outcomes of tapering TNFis experiences of people with RA. The National Rheumatoid Arthritis Control 33% Taper 66% Taper Society (NRAS) wanted to understand how social care is provided, Subjects 50 48 38 which services are required and how satisfied people are. Flares, n (%) 7 (14) 6 (13) 14 (37) Methods: NRAS conducted a literature review of the law, regulations Mean DAS28 (95% CI) after 6 months 2.2 (1.9, 2.4) 2.1 (1.9, 2.3) 2.0 (1.6, 2.3) and policies for social care. Semi-structured and unstructured inter- views were conducted with four individuals with RA and freedom of DAS28: DAS for 28 joints. information requests were sent to 13 local authorities. A focus group was conducted with three individuals with RA and an online questionnaire was designed, piloted and distributed to people with 063. MOTIVATIONAL INTERVIEWING: RELEVANCE IN THE RA and their carers in England. Invitations were sent out electronically TREATMENT OF RHEUMATOID ARTHRITIS? to people with RA and distributed via e-newsletters and social media. 146 respondents completed the survey, a further 161 clicked the link Sofia Georgopoulou1, Louise Prothero1, Heidi Lempp1, but failed to complete it and one person did not meet the qualifying James Galloway1 and Jackie Sturt2 criteria of being resident in England and diagnosed with RA, or caring 1Academic Rheumatology, King’s College London and 2Florence for a person with RA. Nightingale Faculty of Nursing and Midwifery, King’s College Results: Social care is provided through personal relationships: 87% London, London, UK of respondents said family provided care and support, 32% said friends provided this and only 5% named the local authority. Social Background: RA is a systemic, chronic autoimmune disease with care is also funded primarily by family and friends: 56% of respondents symmetrical, inflammatory polyarthritis characterized by periods of said this, while 30% paid for it through welfare benefits and 25% used remission and flares which can be severely disabling and can their own money. There is a lot of unmet need: 92% of respondents significantly influence quality of life. Motivational interviewing (MI) is a said some of their needs were not met, while 9% said none of their patient-centred, counselling approach used in healthcare settings to needs were met. Transport is the largest expenditure: 33% of support patients in developing effective coping and self-management respondents said this, 26% named household cleaning and 17% skills as well as in making lifestyle changes. Depending on the illness, said adaptations to the home. Household cleaning is also the most MI-based psychosocial support provision by healthcare professionals needed service: 68% stated this, while 53% said adaptations to the has generally had positive impact on patients’ physical and psycho- home and 50% said occupational therapy. More information is social status. Very little evidence exists on the impact of MI in required: 87% of respondents had not received information from rheumatology. We developed a training course for a psychosocial local authorities about social care. Access should be lowered: 61% support intervention incorporating MI for rheumatology practitioners said the eligibility threshold for social care should be set at moderate (e.g. nurses, doctors, physiotherapists) treating intermediate RA or low to prevent needs arising. Local authority assessments are patients (DAS for 28 joints score 3.1–5.2). The aim is to increase inadequate: 83% of assessed respondents said it ignored legitimate remission rates and improve patients’ QoL through facilitating needs and 66% said it did not take account of fluctuation in their communication and collaboration between patients and clinicians. condition. Overall, 52% of respondents said most social care they Feasibility and effectiveness of the training and the intervention is received was unsatisfactory. evaluated within a clinical trial: TITRATE. Conclusion: The results suggest people with RA require social care, Methods: The 2-day training course comprises didactic and inter- which is usually provided by family and friends and often does not active seminars and supplemented with a training manual. Feedback meet their needs. To help people with RA obtain social care support from the pilot study conducted in one geographical locality (South East from local authorities, greater information and advice is required and London) in February 2014 indicated the need for minor amendments to the threshold to access social care should be lowered to moderate the content and delivery of the training. The updated training syllabus need. The regulations under the Care Act 2014 should be altered to includes: (a) elements and techniques from MI, e.g. developing trust require consideration of a 12-month period when assessing people and rapport, identifying potential barriers and facilitators for behaviour with fluctuating conditions. change, goal-setting, scheduling activities (exercise, sleep, medication Disclosure statement: The authors have declared no conflicts of intake etc.) and self-monitoring using diaries and worksheets; and (b) interest. i76 Tuesday 28 April 2015 POSTER VIEWING I

065. PREDICTORS OF CLINICAL AND IMAGING REMISSION 3Arthritis Research UK Centre for Genetics and Genomics, University IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS of Manchester, Manchester, UK MANAGED WITH A TREAT-TO-TARGET APPROACH: RESULTS FROM AN EARLY ARTHRITIS CLINIC Background: NICE guidance recommends the use of a combination of DMARDs, to include MTX, in the initial management of patients Sarah C. Horton1,2, Ai Lyn Tan1,2, Richard J. Wakefield1,2, Jane 1,2 1,2 1,2 presenting with RA. Monotherapy is only recommended where there E. Freeston , Maya H. Buch and Paul Emery are contraindications or multiple comorbidities. However, it is not clear 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, 2 how frequently different treatment strategies are used in routine University of Leeds and NIHR Leeds Musculoskeletal Biomedical practice. The aim of this study was to identify, in a national Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK observational cohort, the frequency of MTX monotherapy and examine factors associated with its prescription. Background: ACR/EULAR 2011 remission criteria are recommended Methods: The Rheumatoid Arthritis Medications Study (RAMS) as the optimal therapeutic target in the management of RA. Power recruited patients with RA starting MTX for the first time since 2008 Doppler (PD) activity is detectable in approximately half of patients across the UK. Patients included in this study presented within 2 years with established RA and predicts progression. The aim was to of symptom onset. Data, including demographics, comorbidity, assess the prevalence, relationship and the predictors of clinical and medication history, smoking history, CRP, RF, DAS for 28 joints imaging remission (IR) in early RA, achieved using a treat-to-target (DAS28) and HAQ were recorded at start of therapy. Subsequent approach. medication changes were detailed at 3- and 6-month follow up. Methods: A prospective observational study in patients with newly Patients were classified as being on MTX monotherapy if they did not diagnosed RA was conducted in the Leeds early arthritis clinic. The meet either of the following criteria: currently on another DMARD or treatment target was clinical remission by the DAS in 28 joints (DASR). another DMARD started within 90 days of MTX start date; and Outcomes at 12 months included DASR, ACR/EULAR Boolean currently on oral steroids (for at least 30 days) or started on oral remission (BR) and IR (absence of PD activity in 26 joints). Logistic steroids within 30 days of MTX start date. Univariate and multivariate regression analysis was conducted to identify baseline predictors of logistic regression analysed the association of MTX monotherapy with DASR, BR and IR. Variables with significance (P < 0.05) on univariate baseline age, gender, disease duration, CRP, RF, tender and swollen analysis were entered into multivariate models. Overlapping variables joint counts, HAQ, DAS28, smoking status and comorbidity. [DAS for 28 joints (DAS28)-CRP3v and its components, and radio- Results: A total of 731 patients were included, baseline characteristics graphic and ultrasound-detected erosions] were entered into separate are shown in Table 1. MTX monotherapy was prescribed in 493 (67%) models. patients, of those on combination treatment 193 (80%) were treated in Results: Follow up was available for 210 patients. Management of 162 combination with another DMARD, 48 (20%) with steroids. Older age (77%) was compliant with treat-to-target monitoring, 99% of whom was associated with increased odds of monotherapy and RF positivity received appropriate treatment escalation. Outcomes in patients with with combination therapy (Table 1). complete data were: DASR (DAS28-CRP3v <2.6 mg/l) 103/210 (49%), Conclusion: MTX appears to be more commonly prescribed as BR 20/126 (16%) and IR 66/142 (47%). Neither DASR nor BR were monotherapy than in combination with other DMARDs, despite NICE significantly associated with IR, with IR demonstrated in 37/72 (51%, guidance. In our study, older patients were more frequently treated P ¼ 0.2) and 8/17 (47%, P ¼ 0.8) patients achieving DASR and BR, with monotherapy; however no association was seen with the respectively. Results of univariate analysis for achievement of DASR presence of multiple comorbidities. Others factors not currently and IR were similar in patients with complete data available for incorporated within the guidance, such as patient preference, may assessment of BR and IR (n ¼ 107). Multivariate analysis identified be contributing to these prescribing practices. shorter symptom duration, lower number of comorbidities and lower Disclosure statement: K.L.H. has received honoraria from AbbVie burden of tender joints as independent predictors of DASR, and male and Pfizer. All other authors have declared no conflicts of interest. gender, lower tender joint and DAS28 scores as predictive of BR. A lower total baseline PD activity predicted IR. Conclusion: Half of patients achieved the target DASR. BR was rare. Approximately half of patients achieving clinical remission (DASR or BR) displayed PD activity on ultrasound. The differences observed in 067. DO HEALTH CARE PROFESSIONALS DISCUSS disease characteristics associated with either DASR, BR or IR highlight COMPLEMENTARY MEDICINES WITH RHEUMATOID the complex interaction of symptoms and synovitis and supports ARTHRITIS PATIENTS AS PER NICE GUIDELINES? further investigation of the use of imaging within a treat-to-target Muhamad A. Jasim1, Morven Baker1 and Wahab Al-Allaf1 strategy. 1Rheumatology, New Cross Hospital, Wolverhampton, UK Disclosure statement: The authors have declared no conflicts of interest. Background: RA is a chronic incurable disease with potentially disabling symptoms. This drives many patients to try therapies other 066. ARE CLINICIANS FOLLOWING GUIDANCE FOR than those prescribed by their doctor. The current NICE guidelines on COMBINATION THERAPY IN RECENT-ONSET RHEUMATOID RA recommends healthcare professionals (HCP) discuss complemen- ARTHRITIS? RESULTS FROM A NATIONWIDE tary and alternative medicines (CAM) with all RA patients who are OBSERVATIONAL STUDY (RAMS) considering using them. More specifically, it recommends that patients should be informed of the limited evidence in support of their long- Jenny H. Humphreys1, Jamie Sergeant1,2, James Anderson1, term effectiveness, the importance of continuing with prescribed Anne Barton2,3, Kimme L. Hyrich1,2 and Suzanne M. M. Verstappen1 medications and that using CAM will not prejudice the medical care 1Arthritis Research UK Centre for Epidemiology, University of they receive. The aim of this study was to investigate whether health Manchester, 2NIHR Manchester Musculoskeletal Biomedical care professionals discuss complementary medicines with RA patients Research Unit, Manchester Academic Health Science Centre and as per NICE guidelines?

066 TABLE 1. Baseline characteristics and associations with MTX monotherapy modelled using logistic regression MTX monotherapy (n ¼ 493) Combination therapy (n ¼ 238) Univariate, OR (95% CI) Multivariate, OR (95% CI) Female 326 (66) 161 (68) 0.97 (0.70, 1.36) 1.15 (0.71, 1.86) Age, years 61 (49–70) 56 (45–68) 1.01* (1.00, 1.03) 1.02* (1.00, 1.04) Disease duration, weeks 29 (17–49) 29 (17–51) 1.00 (0.99, 1.01) 1.00 (0.99, 1.01) Swollen joint count 6 (2–11) 6 (2–12) 0.98 (0.96, 1.00) 0.97 (0.94, 1.01) Tender joint count 8 (3–15) 7 (3–15) 1.00 (0.98, 1.02) 1.02 (0.98, 1.05) RF positive, IU/ml 195 (40) 115 (48) 0.60* (0.43, 0.85) 0.46** (0.30, 0.71) CRP, mg/l 6 (3–18) 6 (3–18) 1.00 (0.99, 1.00) 0.99 (0.98, 1.00) HAQ score 1 (0.5–1.625) 1 (0.5–1.625) 1.03 (0.83, 1.29) 0.93 (0.66, 1.33) DAS28 5.12 (3.95–6.13) 4.88 (3.89–6.15) 1.02 (0.91, 1.14) 1.14 (0.87, 1.50) >1 comorbidity 310 (63) 149 (63) 1.01 (0.73, 1.39) 0.76 (0.48, 1.21) Smoking status Current 109 (22) 48 (20) 1.27 (0.84, 1.93) 1.23 (0.69, 2.19) Previous 192 (39) 81 (34) 1.33 (0.93, 1.89) 0.89 (0.54, 1.47) Never 189 (38) 106 (45) ref ref Data are presented as n (%) for categorical variables and median (interquartile range) for quantitative variables; ref in this context means the reference group, i.e. the current smokers and the previous smokers are compared with the never smokers. *P < 0.01, **P < 0.001. DAS28: DAS for 28 joints; OR: odds ratio. POSTER VIEWING I Tuesday 28 April 2015 i77

Methods: A 13 point questionnaire was distributed to RA patients over therapy in patients with deteriorating RA-ILD. A prospective study a 6 week period during October and November 2014 in the similar to that conducted in scleroderma lung disease would now Rheumatology Outpatient Department and day unit at New Cross seem appropriate to confirm these results and define an optimal Hospital, Wolverhampton. treatment regime. Results: A total of 107 patients were sampled, of whom 43% had used Disclosure statement: The authors have declared no conflicts of CAM specifically for their RA. However, a HCP had discussed their use interest. of CAM as per NICE guidelines in only 4% of these cases. In contrast, 64% of the patients who had used CAM acknowledged to having 069. PROGNOSTIC FACTORS FOR INTRAVENOUS never discussed its use with a HCP. Worryingly, almost a quarter of ABATACEPT RETENTION IN PATIENTS WHO HAVE RECEIVED patients (22%) who had used CAM admitted to poorer compliance AT LEAST ONE PRIOR BIOLOGIC AGENT: 2-YEAR RESULTS with their prescribed RA medication. Of all the patients sampled, 63% FROM A PROSPECTIVE, INTERNATIONAL, REAL-WORLD felt that they had not been given enough information about CAM. With STUDY an overwhelming majority (91%) saying they had never discussed CAM with a HCP as the subject was not brought up during Hubert Nu¨ ßlein1, Rieke Alten2, Mauro Galeazzi3, Hanns- consultations. Martin Lorenz4, Michael T. Nurmohamed5, William G. Bensen6, Gerd Conclusion: Our results indicate that despite the widespread use of R. Burmester7, Hans-Hartmut Peter8, Peter Peichl9, Karel Pavelka10, CAM among patients with RA, HCPs appear to be failing to discuss its Melanie Chartier11, Coralie Poncet12, Christiane Rauch13 and use in accordance with NICE guidelines. As a consequence, we risk Manuela Le Bars14 patients gaining false or inaccurate information. In turn, patients may 1Rheumatology, Internistische Schwerpunktpraxis, Nu¨ rnberg, develop unrealistic expectations, and this may contribute to a poorer Germany, 2Rheumatology, Schlosspark-Klinik University Medicine, compliance with their prescribed medication. Clearly, RA patients Berlin, Germany, 3Rheumatology, University of Siena, Siena, Italy, seem to want more information about CAM, therefore HCP should do 4Rheumatology, University Hospital, Heidelberg, Germany, more to address this. 5Rheumatology, VU University Medical Centre/Jan van Breeman Disclosure statement: The authors have declared no conflicts of Research Institute, Amsterdam, The Netherlands, 6Department of interest. Medicine, St Joseph’s Hospital and McMaster University, Hamilton, ON, Canada, 7Rheumatology and Immunology, Charite´ , University 8 068. CYCLOPHOSPHAMIDE IN THE TREATMENT OF Medicine Berlin, Berlin, Centre of Chronic Immunodeficiency, University of Freiburg, Freiburg, Germany, 9Internal Medicine, SEVERE INTERSTITIAL LUNG DISEASE IN PATIENTS WITH 10 RHEUMATOID ARTHRITIS Evangelisches Krankenhaus, Vienna, Austria, Institute of Rheumatology and Clinic of Rheumatology, Charles University, Uma Karjigi1, Judith Gordon1, Evelyn Palmer1, David Middleton2, Prague, Czech Republic, 11Real World Research Department, Mohammed Nisar3, Adam Young4, Julie Dawson5, Subha Arthanari3, Chiltern International, Neuilly, 12Biostatistics, Docs International, 6 7 5 Felix Woodhead , Alex Forbes-Price , Nav Sathi , Se` vres, France, 13Medical Affairs Immunoscience, Bristol-Myers 8 4 1 Yasmeen Ahmed , Gouri Koduri and Clive Kelly Squibb, Munich, Germany and 14Medical Affairs, Bristol-Myers 1 2 Queen Elizabeth Hospital, Rheumatology, Gateshead, Aberdeen Squibb, Rueil-Malmaison, France Hospital, Rheumatology, Aberdeen, 3Burton Hospital, 4 Rheumatology, Burton, St Albans Hospital, Rheumatology, Background: To identify prognostic factors of retention for abatacept St Albans, 5Wrightington Hospital, Rheumatology, St Helens, (ABA) treatment in patients with moderate-to-severe RA, using final 6Walsgrave Hospital, Chest Medicine, 7Walsgrave Hospital, results from the real-world ACTION study. Rheumatology, Coventry and 8Betsi Cadwallydr Hospital, Methods: ACTION was a 2-year follow up, non-interventional, Rheumatology, North Wales, UK international, multicentre, cohort study that evaluated retention and effectiveness of i.v. ABA in adults with moderate-to-severe RA in Background: There is little evidence base to guide clinicians in the Europe and Canada (May 2008 to January 2011). Socio-demo- management of patients with RA-related interstitial lung disease (ILD). graphics, disease characteristics, previous/concomitant therapies In the subgroup of patients who have rapidly deteriorating respiratory and comorbidities at ABA initiation were considered potential prog- function, pulsed CYC has been advocated but no assessment of its nostic variables of retention. Patients who had received 1 prior efficacy has been published. The British Rheumatoid Interstitial Lung biologic agent in countries with sufficient patient numbers to explore (BRILL) network has collected data on the treatment and outcomes of between-country effects were included. Clinically relevant variables, 260 patients with RA-ILD, which allow assessment of this therapeutic known risk factors and prognostic factors with a p 0.10 (univariate strategy. analysis) were entered into a multivariate Cox proportional hazards Methods: We identified 260 patients across 16 UK centres who met regression model, with clustered data adjusted for one investigator. the 2010 EULAR criteria for RA and had confirmation of ILD on high- Factors with p 0.10 after backward selection were retained in the resolution CT (HRCT) of the lungs. We analysed demography, all drug final model. Co-linearity and interactions were assessed. Additional therapy, duration of disease, subtype and extent of ILD on HRCT, analysis to account for missing data in covariates was performed using smoking history, serology and baseline pulmonary function. For each multiple imputation by chained equations. patient who had received pulsed i.v. CYC, we identified two case Results: 1009/1131 (89.2%) evaluable patients had failed 1 prior controls with RA-ILD who had never received this drug and who were biologic agent. The crude retention rate (95% CI) at 24 months matched for age, gender, disease subtype and extent. We compared (Kaplan–Meier method) for patients exposed to 1 prior biologic agent duration of both RA and of ILD between the two groups, as well as vital was 53.4% (50.1, 56.6%). 995 of 1009 patients were included in the capacity (VC) and gas transfer [carbon monoxide transfer factor analysis of prognostic factors. Final multivariate model results (n ¼ 916) (TLco)]. Mortality and mean survival times in each group were are shown in Table 1. Patients had significantly higher likelihood of compared. ABA retention if they were both RF and ACPA positive or had Results: We identified 21 patients who had received pulsed CYC for cardiovascular comorbidity at initiation. Prior anti-TNF agents, high progressive RA-ILD. Ten were male and the group median age was 71 baseline ESR and CS use were also prognostic factors for disconti- (58–86) years. Most patients were smokers (13/21) and all were nuation. Despite showing borderline significance in the first model, use seropositive. Median duration of ILD and RA were 2 and 11 years of a non-anti-TNF biologic agent before ABA (n ¼ 143, 15.6%) was an respectively in both the CYC treated group and in the case controls. In additional prognostic factor of lower retention [1.29 (1.00, 1.66); both groups, 14 patients had UIP (with 7 NSIP) and 14 patients had P ¼ 0.049] in the model with imputation of missing data (not shown). extensive disease (with 7 limited). Median baseline % predicted VC Disease duration, ABA monotherapy and BMI were not identified as (range) was lower in the CYC patients at 71% (40–117%) than in case prognostic factors. controls 84% (55–134%) (P ¼ 0.015), as was TLco at 45% (25–109%) Conclusion: ACTION is one of the first studies to identify and report vs 57% (27–82%) (P ¼ 0.04). Mortality was identical between the prognostic factors of long-term abatacept retention in a real-world groups at 24%, with mean survival better in those treated with CYC setting. Double ACPA and RF positivity and cardiovascular comorbid- than in case controls (72 vs 43 months, P ¼ 0.13). Pulmonary function ity at initiation were prognostic of higher retention. Consistent with was comparable among those who survived in the group treated with other reports, higher number of prior anti-TNFs, country and more CYC to those who died in the control group. severe disease (suggested by higher baseline ESR and introduction of Conclusion: This data from the BRILL network shows that the use CS) were identified as prognostic factors of lower retention. These of pulsed CYC for patients with progressive RA-ILD is associated results will support individualized biologic treatment strategies in with mortality and survival at least as good as in RA-ILD patients with patients with moderate-to-severe RA. lesser impairment of baseline pulmonary function. Indeed, those Funding statement: This study was supported by BMS. who died in the control group may have survived if they had received Disclosure statement: H.N. has received consulting fees from BMS, CYC. This retrospective analysis supports the early use of such Abbott, Chugai, UCB, Essex, Wyeth, Pfizer, MSD, Novartis and Roche. i78 Tuesday 28 April 2015 POSTER VIEWING I

R.A. has received consulting fees from BMS; and has received benefit body composition and physical function. Pertinently, restora- research funding from BMS. H.M.L. has received consulting fees from tion of normal function is an explicit aim of EULAR and ACR BMS. M.T.N. has received consulting fees from BMS, Janssen; has recommendations and principles for T2T. This cross-sectional study served on speakers’ bureaus on behalf of Roche, AbbVie, Pfizer and evaluated the effect of T2T on body composition and objectively UCB; and has received research grants from Roche, AbbVie, Pfizer, assessed function. MSD, UCB and BMS. W.G.B. has received consulting fees from Methods: Sixty-eight RA patients, diagnosed and exclusively treated Abbott, Amgen, BMS, Janssen, Merck, Lilly, Novartis, Pfizer, Proctor in the T2T era (post 1/1/08) were compared with 81 age- and sex- and Gamble, Roche, Sanofi-Aventis, Schering, Takeda, UCB, Warner matched, sedentary healthy controls (HC). To provide an indication of Chilcott and Wyeth; has served on speakers’ bureaus on behalf of the time-course of rheumatoid cachexia, the RA patients were further Abbott, Amgen, BMS, Janssen, Merck, Lilly, Novartis, Pfizer, Proctor divided into those with recent-onset disease (diagnosis and treatment and Gamble, Roche, Sanofi-Aventis, Schering, Takeda, UCB, Warner initiation within 12 months of assessment; n ¼ 27) and those with Chilcott and Wyeth; and has received research grants from Abbott, established disease (12 months since diagnosis and commencing Amgen, BMS, Janssen, Merck, Lilly, Novartis, Pfizer, Proctor and treatment; n ¼ 41). Body composition was assessed by DXA, with the Gamble, Roche, Sanofi-Aventis, Schering, Takeda, UCB, Warner summed lean masses of the arms and legs (appendicular LM; ALM) Chilcott and Wyeth. G.R.B. has received consulting fees from used as a surrogate measure of total MM. Physical function was AbbVie, BMS, MSD, Medimmune, Novartis, Pfizer, Roche, Sandoz objectively assessed by knee extensor strength, handgrip strength, and UCB; has served on speakers’ bureaus on behalf of AbbVie, BMS, 30 s sit-to-stand, 8 min up and go, and 50 min walk tests (a battery of MSD, Pfizer, Roche, Sandoz, UCB; has received research grants from tests designed to reflect the ability to perform activities of daily living), AbbVie, Pfizer, Roche and UCB. K.P. has received consulting fees and subjectively assessed by HAQ (0–3 scale) from MSD, AbbVie, Pfizer, UCB, Roche, Amgen, Menarini and BMS. Results: Despite low disease activity, RA patients had significantly M.C. has received consulting fees from BMS. C.P. has received reduced ALM relative to body weight (11%) and, proportionally, were consulting fees from BMS. C.R. is an employee of BMS. M.L.B. is an considerably fatter (15%), particularly in the trunk (34%), than employee and shareholder of BMS. All other authors have declared no matched-HCs. Objectively assessed physical function was consis- conflicts of interest. tently 25–35% poorer in the RA patients relative to HC, although perceived disability was deemed only mild (mean HAQ ¼ 0.6). All measures of body composition and physical function were identical or 069 TABLE 1. Final multivariate model of abatacept retention without imputation of missing data (n ¼ 916) very similar for recent-onset and established RA patients (data not presented). Mean DAS for 28 joints (DAS28) scores for both patient Prognostic factor HR 95% CI P-value groups were 2.8. Baseline demographic characteristics Conclusion: Despite marked improvements in disease control (most Country <0.001 patients achieving or approaching remission, i.e. DAS28 <2.6), the Germany 1.00 relative loss of MM and the increase in fat mass compared with Czech Republic 1.40 0.74, 2.65 Canada 1.23 0.93, 1.64 matched-HCs is similar to that reported pre-T2T. Similarly, despite Austria 0.97 0.51, 1.84 lower HAQ scores, the deficits in performance of the objective physical Netherlands 0.76 0.34, 1.71 function tests (25–35% poorer) are identical to those previously Italy 0.61 0.42, 0.89 observed. Thus, T2T, even in responsive RA patients, has not Greece 0.55 0.37, 0.83 attenuated the adverse changes in body composition, and conse- Baseline disease characteristics quently not reduced objectively assessed measures of disability. RF/anti-CCP double positivity <0.001 These results suggest that the perturbations in body composition No 1.00 Yes 0.64 0.49, 0.84 occur very early, probably prior to diagnosis and initiation of treatment Not available 0.63 0.47, 0.85 and indicate that to restore physical function, interventions that ESR,mm/h 0.031 improve body composition are required. 1.00 Disclosure statement: The authors have declared no conflicts of 17- 1.31 0.97, 1.78 interest. 30- 0.92 0.69, 1.22 51 mm/h 1.38 1.03, 1.84 Not done 1.11 0.74, 1.67 071. SULFASALAZINE USE IS ASSOCIATED WITH REDUCED Cardiovascular comorbidity 0.004 No 1.00 MORTALITY IN RHEUMATOID ARTHRITIS ASSOCIATED Yes 0.51 0.32, 0.81 INTERSTITIAL LUNG DISEASE Number of prior anti-TNF agents 0.001 Jessica J. Lee1, Riwa Meshaka1, Emma J. Helm2, Alec N. Price- 0–1 1.00 1 1 3 2 1.42 1.15, 1.76 Forbes , Shirish Dubey and Felix A. Woodhead 1 Type of prior biologic agent 0.057 Rheumatology, University Hospital Coventry and Warwickshire, Anti-TNF agent 1.00 2Radiology, University Hospital Coventry and Warwickshire, Coventry Other mechanism of action 1.29 0.99, 1.68 and 3Respiratory Medicine, Glenfield Hospital, Leicester, UK Concomitant treatments CS treatment pattern at initiation 0.04 Background: 7% of patients with RA have clinically significant (vs before initiation) No CS or stop CS 1.00 interstitial lung disease (RA-ILD) which significantly increases morbid- Continuous use of CS 0.99 0.78, 1.25 ity and mortality. Anti-TNF agents have been associated with Introduction of CS 1.41 1.03, 1.92 significant lung injury in a small number of patients, with high morbidity and mortality. It is common practice for MTX to be avoided or stopped in patients with significant ILD, although there are no data to suggest increased mortality or morbidity due to MTX. AZA use had been associated with increased mortality in British Society Rheumatology 070. TREAT-TO-TARGET TREATMENT FAILS TO RESTORE biologics register (BSRBR), but was thought to be due to RA-ILD, EITHER BODY COMPOSITION OR OBJECTIVELY ASSESSED rather than AZA. We interrogated our database for any association PHYSICAL FUNCTION IN RHEUMATOID ARTHRITIS PATIENTS between use of medications and mortality, with a particular interest in the effect of MTX and anti-TNF agents. Andrew B. Lemmey1, Rebecca Clayton1, Thomas Wilkinson1, Methods: We retrieved the reports of all high-resolution CT (HRCT) Fazal Sheikh2, Yasmeen Ahmad2, John Whale1, Hope Jones1, scans requested by consultant rheumatologists at University Hospital Sarang Chitale2, Jeremy Jones2, Peter Maddison1 and Coventry and Warwickshire NHS Trust during a 6 year period (1 June Thomas O’Brien1 2006 to 31 December 2012). We identified patients with RA-ILD and 1School of Sport, Health & Exercise Sciences, Bangor University, collected available smoking and drug histories retrospectively from Bangor and 2Peter Maddison Rheumatology Centre, BCUHB, medical records. We recorded mortality and length of follow up. Llandudno Hospital, Llandudno, UK Univariate associations with mortality were examined by Cox’s proportional hazards using Rstatistics. Background: Historically RA has been characterized by adverse Results: 484 patients had HRCT scans during the study period. 76 changes in body composition (loss of muscle mass (MM) and (16%) were confirmed to have a diagnosis of RA-ILD based on HRCT excessive fat mass, especially trunk fat mass), termed rheumatoid findings of ILD and a clinical history of RA. 51 out of 76 (67%) patients cachexia. In turn, rheumatoid cachexia contributes to physical were alive at the end of the study. The median (range) time between disability. Since rheumatoid cachexia is thought to be driven by diagnostic HRCT and death was 24 (0.6–83) months. 15 of 25 died inflammation, it would be anticipated that the success of treat-to- more than 6 months after HRCT diagnosis (Table 1; analysis after target (T2T) in reducing inflammation and disease activity would also missing data excluded). No significant association was found between POSTER VIEWING I Tuesday 28 April 2015 i79

smoking or anti-TNF use and mortality. Neither was there any 073. BIOLOGIC DMARD USE IN A LOCAL POPULATION OF association with MTX or AZA use. We did find a reduced hazard RHEUMATOID ARTHRITIS PATIENTS IN THE UK, 2004–2014 ratio for mortality with SSZ use which, to our knowledge, has not been 1 1 1 reported before. It is unclear if this reflects milder disease. Stephanie Spring , Maeve McLaughlin , Andrew Ostor and Elena Nikiphorou2 Conclusion: We report the surprising association between SSZ use 1 2 and a reduced hazard ratio of mortality in a retrospective cohort of Rheumatology Clinical Research Unit and Rheumatology, patients with RA-ILD. This needs to be examined in bigger studies to Addenbrooke’s Hospital, Cambridge, UK see if the association is genuine. Disclosure statement: The authors have declared no conflicts of Background: Biologic agents were first licensed in the UK in 2002 and interest. have resulted in a dramatic improvement in outcomes for patients with uncontrolled RA. However, following the benefits of early treatment

071 TABLE 1. Risk factors and mortality in RA-ILD: univariate predictors with intensive synthetic DMARD combinations, and the introduction of early RA clinics, it may be anticipated that biologic DMARD use would Factor Exposed/not Hazard ratio P-value decline over time. We examined the use of biologic DMARDs in RA exposed/missing data, n (95% CI) patients since the establishment of the early RA clinic in Cambridge in Ever smoked 46/23/7 1.75 (0.64, 4.79) 0.253* 2004. Ever had anti-TNF 9/53/14 1.23 (0.41, 3.66) 0.717* Methods: Interrogation of our institution’s electronic database was Ever had MTX 41/35/0 0.75 (0.34, 1.65) 0.475 Ever had SSZ 41/35/0 0.39 (0.17, 0.92) 0.024 undertaken to identify consecutive patients with RA who received their Ever had HCQ 29/47/0 0.72 (0.30, 1.73) 0.449 first biologic agent between January 2004 and June 2014. The Ever had AZA 11/66/0 1.92 (0.71, 5.19) 0.227 database contains data on diagnosis, clinical and laboratory variables and treatment details for patients attending the Rheumatology Department. Results: A total of 542 patients with RA (77% female) were started on their first biologic DMARD between 2004 and 2014. Of these, 299 072. THE ASSOCIATION BETWEEN ORAL (55%) were seropositive and 36% had erosive disease. Mean age at GLUCOCORTICOID THERAPY AND MORTALITY IN PATIENTS commencement of biologic DMARD was 55.9 years (S.D. 13.66). WITH RHEUMATOID ARTHRITIS: A RETROSPECTIVE Biologic DMARDs used were adalimumab (49%) etanercept (27%), COHORT STUDY rituximab (11%), infliximab (8%), abatacept (2%) and golimumab (2%).

1 1,2 1 Graphical displays will demonstrate the differences in the type of first Mohammad Movahedi , Jamie C. Sergeant , Mark Lunt , Stephen biologic used across this population over the past 10 years. Significant R. Pye1 and William G. Dixon1 1 differences were noted in the age of patients commencing different Arthritis Research UK Centre for Epidemiology, Centre for types of biologics (P ¼ 0.004). Patients starting infliximab had the Musculoskeletal Research, Manchester Academic Health Science S D 2 lowest mean age (52.8, . . 13.1) compared with the rest of the Centre and NIHR Manchester Musculoskeletal Biomedical Research patients. The highest patient mean age at commencing a biologic was Unit, Central Manchester University, Hospitals NHS Foundation noted for rituximab (mean 61.7, S.D. 12.4). There was no significant Trust, University of Manchester, Manchester, UK difference in the choice of biologic DMARD based on gender (P ¼ 0.320). Graphs will show the average new biologic starts per Background: Glucocorticoid (GC) therapy is used by more than 50% month in 6-monthly periods between 2004 and 2014. of patients with RA. GCs reduce joint pain, swelling and stiffness. Conclusion: Our results suggest that first biologic DMARD use has However, there are concerns about side effects, including increased remained static over the last 4 years with a recent trend downwards. mortality. This study aimed to examine the impact of oral GC use on Reasons for this may be the impact of early RA clinics and the earlier all-cause and cardiovascular (CV) mortality in patients with RA. and more intensive use of synthetic DMARDs. Other possibilities may Methods: In a retrospective cohort study design, patients with RA include the presentation of disease in a milder form in more recent were identified in the Clinical Practice Research Datalink (CPRD), a years or patient and/or physician-related reasons including individual research database of anonymized UK primary care electronic medical preferences and thresholds for various treatments. The observed records. Oral GC exposure was identified from prescriptions. Mortality decline in the use of biologics is paralleled by a lower number of data, including cause of death, were obtained through linkage to the patients recruited into clinical trials. UK Office for National Statistics. All-cause and CV mortality rates are Disclosure statement: The authors have declared no conflicts of presented as rates per 100 person-years (pyrs) with 95% CIs. interest. Multivariable time-dependent Cox models assessed the association between patterns of GC use (ever use, current daily dose category, and cumulative dose category since cohort entry) and death, adjusting 074. EFFICACY AND SAFETY OF BIOSIMILAR RITUXIMAB IN for potential confounders including age, gender, BMI, smoking, BIOLOGIC NAI¨VE PATIENTS WITH RHEUMATOID ARTHRITIS: comorbidity, socioeconomic status, prior steroid use, RA disease A SINGLE CENTRE EXPERIENCE FROM KERALA, INDIA duration and DMARD concomitant use. Results: We studied 21 280 patients with a median follow up of Vinod Ravindran1 5.4 years. 1231 deaths were identified during 7851 pyrs in patients not 1Department of Rheumatology, National Hospital, Calicut, India yet exposed to GC therapy (1.57 events/ 100 pyrs) (95% CI 1.48, 1.66) and 2355 in 5205 pyrs in those ever-exposed [4.52 events/100 pyrs Background: Rituximab, an anti-CD20 mAb is widely used in the (95% CI 4.35, 4.71)]. Adjusted hazard ratio (aHR) of all-cause mortality treatment of RA. A biosimilar rituximab has been commercially was 2.26 (95% CI 2.06, 2.47) in ever GC use compared with never GC available in India since 2007. Biosimilar rituximab is cheaper and use. Compared with non-use, a current low dose of GC therapy potentially could be even more cost effective in biologic naive RA (<5 mg prednisolone equivalent per day) was associated with a patients compared with the anti-TNF therapies. However, very limited reduced risk of mortality (aHR 0.79 [95% CI 0.66, 0.95)]. The mortality data exists on the safety and efficacy of biosimilar rituximab in such rate was increased in patients receiving doses above 5 mg. The aHRs patients. for 5–7.5 mg/ day was 1.17 (95% CI 1.01, 1.35); 7.5–15 mg/ day 1.73 Methods: All consecutive adult patients with RA who continued to (95% CI 1.50, 2.00), 15–25 mg 3.97 (95% CI 3.11, 5.08) and 6.95 (95% have active disease [DAS for 28 joints (DAS28)-ESR 5.1 mm/h] CI 5.31, 9.10) for doses above 25 mg. CV deaths were similarly lower in despite standard combination DMARDs therapy (including MTX) and patients receiving doses of less than 5 mg, although this was not therefore consented to treatment with biosimilar rituximab (2 doses of statistically significant [aHR 0.82 (95% CI 0.61, 1.10)] and higher for 1000 mg, 2 weeks apart) were included in this retrospective analysis. doses above 5 mg. All patients were assessed in the standard care which comprised Conclusion: Low dose oral GC therapy appeared to have a protective follow-up assessments once every 3 months and DAS28-ESR and effect on all-cause mortality in RA patients. However, a current oral GC HAQ (Indian version) measurements, and recording any adverse dose higher than 5 mg per day and increasing cumulative doses were events. significantly associated with an increased risk of both all-cause and CV Results: Fourteen patients (mean age 56 4.2 years; 65% females) mortality, although residual confounding may explain some of these were included over a 3 year period (follow-up range, 8–36 months). associations. Three had interstitial lung disease (ILD) and two had rheumatoid Disclosure statement: M.M. has received research funding from the vasculitis causing peripheral neuropathy. At 24 weeks compared with MRC. W.G.D. has received research funding from the MRC. All other the baseline, both DAS28-ESR (5.36 0.15 mm/h vs 2.54 0.8 mm/h, authors have declared no conflicts of interest. P < 0.0001) and HAQ (1.98 0.54 vs 1.14 0.31, P < 0.0001) showed significant improvement. Sustained remission (range, 8–24 months) was achieved in 12 and 1 had moderate but sustained response. De-escalation of existing therapy including of glucocorticoids was i80 Tuesday 28 April 2015 POSTER VIEWING I

possible in 9 patients. Two patients were retreated with biosimilar tocilizumab (TCZ) compared with other traditional and biologic rituximab, one after 12 months and another after 24 months. In the only DMARDs (tDMARDs and bDMARDs) in adult patients with moderate- nonresponder a different class of biologic agent was considered. In to-severe ERA naive to MTX or bDMARDs. three patients with ILD, no worsening was documented after a mean Methods: A literature review identified randomized controlled trials follow up of 16 months. Infusion reactions were none and no serious (RCTs) of tDMARDs and bDMARDs in patients with ERA (duration <3 adverse events were observed. years) reporting efficacy outcomes (proportions of patients achieving Conclusion: In this cohort of biologic naive patients with active RA, ACR scores of 20, 50, 70 and 90; DAS for 28 joints (DAS28)-defined use of biosimilar rituximab demonstrated prolonged benefit in a remission (DAS28 <2.6). Bayesian network meta-analysis was majority and was well tolerated. performed. For ACR response, data were analysed using a fixed- Disclosure statement: The author has declared no conflicts of effects (FE) ordered probit model. For DAS remission, data were interest. analysed with an FE binomial logit model. The analysis included only results for treatments at licenced doses. Sensitivity analyses were performed for treatment class and inclusion criteria. 075. OPTIMAL MANAGEMENT OF FOOT AND ANKLE Results: 16 RCTs of tDMARDs (MTX, SSZ, HCQ), bDMARDs DISEASE IN RHEUMATOID ARTHRITIS: IS A TREAT-TO- [abatacept (ABT), adalimumab (ADA), etanercept (ETN), infliximab TARGET DAS DRIVEN PROTOCOL ADEQUATE? (IFX), golimumab (GOL), TCZ), and tofacitinib (Tofa) were included. All Aamir Saeed1, Aizad Mumtaz1, Shona Lee1, Ronan Mullan1 and bDMARDs plus MTX, triple tDMARD therapies, and TCZ and Tofa in David Kane1 monotherapy significantly increased response across all ACR cate- 1Rheumatology, Adelaide & Meath Hospital, Dublin, Ireland gories versus MTX. Probabilities of ACR response to bDMARDs plus MTX were broadly similar, with no significant differences between Background: Erosive foot and ankle disease can be presenting agents. Probabilities of ACR response to bDMARDs in monotherapy feature in 30–50% of RA patients. Musculoskeletal US (MSKUS) is were more varied, with a trend toward higher values for Tofa and TCZ helpful in detecting synovitis with greater sensitivity and specificity than for ETN or ADA. Only a subset of studies reported DAS remission. than clinical examination. The EULAR recommends a treat-to-target Treatment with Tofa or any bDMARD (MTX), except ADA alone, (T2T) protocol for RA. The DAS for 28 joints (DAS28)-CRP is currently improved the likelihood of DAS remission versus MTX. TCZ ( MTX) used in a T2T protocol but does not include assessment of foot and generated the highest probability of remission among bDMARDs and ankle, which are commonly involved in RA. This study comprehen- was significantly more effective than all other bDMARDs (MTX) and sively evaluated the effectiveness of a DAS28-CRP T2T protocol on Tofa. Results were robust to sensitivity analyses. foot and ankle disease using standardized clinical and functional Conclusion: Based on ACR response, the expected efficacy of scores and US in patients with RA. bDMARDs plus MTX, Tofa and TCZ monotherapy, and triple tDMARD Methods: 18 consecutive patients attending Rheumatology outpatient therapy appears comparable in early RA. TCZ and Tofa in mono- clinics with established RA commencing biologic treatment as per T2T therapy are more effective than ADA alone and are likely to be more protocol were selected. Patients were assessed at baseline and 6 effective than ETN alone. TCZ MTX is expected to have the highest months with ESR, CRP, DAS for 28 joints (DAS28), metrology of ankles probability of generating DAS remission. and feet, Leeds Foot Impact Scale (LFIS) scores and US of feet and Disclosure statement: L.S. has acted as a consultant for Roche. S.C. ankles (AS Level 1 ultrasonographer). All relevant clinical and US has acted as a consultant for Roche. A.D. has acted as a consultant for findings at baseline and 6 months were recorded and analysed. Roche. F.D. is an employee of Roche. Results: 16 patients (15 females, mean age 47 years, mean disease duration 46 months) completed the study. 2 patients were excluded as they were unable to attend for follow-up visit because of concurrent 077. HIGHER CUMULATIVE DOSE OF METHOTREXATE illness. 94% of Patients were on DMARDs prior to commencing DURING THE FIRST 12 WEEKS SEEMS TO BE ASSOCIATED biologic treatment (etanercept, 8; adalimumab, 5; abatacept, 1; WITH BETTER RESPONSE IN PATIENTS WITH RHEUMATOID golimumab, 1; and rituximab, 1) for 6 months. Significant improve- ARTHRITIS ments were observed in DAS28 CRP (P < 0.001), tender (tender joint Suzanne M. M. Verstappen1, James Anderson2, Anne Barton2,3 and count; P < 0.001) and swollen feet joint count (SJC) P < 0.01 in Kimme L. Hyrich1 comparison with baseline. Non-significant improvements were 1Arthritis Research UK Centre for Epidemiology, University of demonstrated in feet US (grey and power Doppler scores) and LFIS Manchester, 2NIHR Manchester Musculoskeletal Biomedical scores (Table 1). 60% of DAS28 remission patients at 6 months Research Unit, Manchester Academic Health Science Centre and showed subclinical disease with LFIS and grey-scale US. 3Arthritis Research UK Centre for Genetics and Genomics, University Conclusion: A DAS28-CRP T2T protocol is effective in managing clinical of Manchester, Manchester, UK foot and ankle disease in most RA patients but significantly under- estimates synovitis compared with US as a gold standard. US synovitis Background: MTX is the DMARD of first choice in patients with RA. at foot and ankle is associated with the progression to joint damage. US Recommendations state that oral MTX should be started at 10–15 mg/ should be used to define true foot and ankle disease remission. week, with escalation of 5 mg every 2–4 weeks up to 20–30 mg/week. Disclosure statement: The authors have declared no conflicts of The aim of this study was to assess the association between starting interest. dose of MTX and cumulative dose of MTX in the first 3 months after MTX commencement with EULAR good response. Methods: Since 2008 patients with RA commencing MTX for the first 075 TABLE 1. Comparison of 0- and 6-month observations time are recruited to the Rheumatoid Arthritis Medication (RAMS) Category 0 month 6 month P-value study, a multicentre (n ¼ 35) observational cohort study in the UK. At DAS-CRP, mg/l, mean (S.E.M.) 4.8 (0.23) 2.6 (0.26) <0.001 baseline and 6 months DAS for 28 joints scores are calculated and TJC, mean (S.E.M.) 8.25 (0.78) 3.68 (0.75) <0.001 EULAR response criteria are applied. Starting dose of MTX, dose SJC, mean (S.E.M.) 4.37 (0.67) 1.93 (0.69) <0.01 increment and any changes in dose of MTX are recorded at baseline, 3 LFIS, mean (S.E.M.) 28.1 (3.4) 24.8 (3.3) 0.21 and 6 months follow-up assessments. Only patients with available GSUS, mean (S.E.M.) 12.7 (1.3) 9.0 (2.0) 0.09 EULAR response data at 6 months and still on MTX after 12 weeks PDUS, mean (S.E.M.) 2.88 (1.1) 1.3 (0.89) 0.2 were included in this study. The predictive ability between starting GSUS: grey-scale US; LFIS: Leeds Foot Impact Scale; PDUS: power Doppler US; dose of MTX and cumulative dose of MTX over the first 12 weeks and SJC: swollen joint count; TJC: tender joint count. EULAR response (good vs poor and good vs moderate) was assessed applying logistic regression analysis. In addition, receiver operator curves (AUC ROC) were calculated and compared. 076. EFFICACY OF BIOLOGIC TREATMENTS IN EARLY Results: 575 RA patients with a median symptom duration of 10 ACTIVE RHEUMATOID ARTHRITIS: AN INDIRECT (interquartile range 5–29) months and a mean age of 58 (S.D.14)years COMPARISON were included in this study. Overall, starting dose of MTX varied considerably between participating centres, and to a lesser extent within 1 1 1 Laura Sawyer , Stacey Chang , Alex Diamantopoulos and centres, ranging from 2.5 mg/week to 25 mg/week [mean 11.6 (S.D.3.1) Fred Dejonckheere2 mg/week]. Most patients started on oral MTX (98.2%). Six months after 1Health Economics and Outcomes Research, Symmetron Limited, MTX commencement 29% patients had a EULAR good response, 26% Herts, UK and 2International Payer Strategy, F. Hoffmann-La Roche, a moderate response and 45% a poor response. Starting dose of MTX Basel, Switzerland was not associated with achieving a good response [mean MTX dose 11.8 (S.D. 3.0) mg/week] at 6 months compared with having a poor Background: No head-to-head trials have compared biologic treat- response [mean dose of MTX 11.5 (S.D. 3.1) mg/week] (OR 1.04 95% CI ments for early active RA (ERA). We evaluated the effectiveness of 0.98, 1.11). Although there was a trend toward a statistical POSTER VIEWING I Tuesday 28 April 2015 i81

significant association between the 12 week cumulative dose of MTX with response (good vs poor response, response 174 (S.D.39)vs 167 079. DO ULTRASOUND (POWER DOPPLER (S.D. 42) mg, OR 1.004 95% CI 1.00, 1.01, P ¼ 0.078), the AUC of the ROC curves were not statistically significant different (P ¼ 0.219). No ULTRASONOGRAPHY) AND DISEASE ACTIVITY SCORE-28 differences were observed between good and moderate EULAR MEASURE DIFFERENT ASPECTS OF DISEASE ACTIVITY? responders. ANALYSES FROM AN OPEN-LABEL STUDY OF POWER Conclusion: Higher cumulative dose of MTX during the first 3 months DOPPLER ULTRASONOGRAPHY RESPONSE PATIENTS WITH of MTX treatment may be more beneficial, but future studies are RHEUMATOID ARTHRITIS PATIENTS STARTING ABATACEPT necessary to investigate if this small beneficial effect may outweigh Maria A. D’Agostino1, Maarten Boers2, Richard J. Wakefield3, possible negative effects such as more adverse events. Hilde B. Hammer4, Olivier Vittecoq5, Mauro Galeazzi6, Peter Balint7, Disclosure statement: The authors have declared no conflicts of Ingrid Mo¨ ller8, Annamaria Iagnocco9, Esperanza Naredo10, interest. Mikkel Østergaard11, Corine Gaillez12 and Manuela Le Bars13 1Rheumatology Department, AP-HP Ambroise Pare´ Hospital, 2 078. A PARADOXICAL RELATIONSHIP BETWEEN BAFF AND Boulogne-Billancourt, France, Departments of Epidemiology & Biostatistics, Rheumatology, VU University Medical Centre, B CELLS REVEALED BY RITUXIMAB THERAPY FOR 3 RHEUMATOID ARTHRITIS Amsterdam, The Netherlands, Leeds Institute of Rheumatic and Musculoskeletal Disease, University of Leeds/Leeds Teaching Yasser El-Sherbiny1,2, Frederique Ponchel1,2, Andrew C. Rawstron3, Hospital Trust, Leeds, UK, 4Department of Rheumatology, Paul Emery1,2 and Edward M. Vital1,2 Diakonhjemmet Hospital, Oslo, Norway, 5Rheumatology Department, 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University Hospital, Rouen, France, 6Rheumatology, University of University of Leeds, 2NIHR Leeds Biomedical Research Unit, Leeds Siena, Siena, Italy, 73rd Rheumatology Department, National Institute Teaching Hospitals NHS Trust and 3Haematological Malignancy of Rheumatology and Physiotherapy, Budapest, Hungary, Diagnostic Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK 8Department of Rheumatology, Instituto Poal, Barcelona, Spain, 9Dipartimento Medicina Interna e Specialita` Mediche, Sapienza Background: B cell subset analysis shows that depletion and Universita` di Roma, Roma, Italy, 10Department of Rheumatology, repopulation of plasmablasts (a small subpopulation derived from Hospital Universitario Severo Ochoa and Hospital GU Gregorio the differentiation of activated B cells) predicts clinical response and Maran˜ o´ n, Madrid, Spain, 11Copenhagen Centre for Arthritis relapse. However, the determinants of B cell subpopulation numbers Research, Copenhagen University Hospital at Glostrup, are unknown. The B cell activating factor (BAFF) system is crucial in B Copenhagen, Denmark, 12(formerly of) Medical Affairs, Bristol-Myers cell homeostasis. However, the system is complex. It includes two Squibb, Rueil-Malmaison and 13Medical Affairs, Bristol-Myers ligands (BAFF and BLyS); and A Proliferation-Inducing Ligand (APRIL)] Squibb, Rueil-Malmaison, France and three receptors [BAFF-receptor (BAFF-R); Transmembrane- Activator and CAML-Interactor (TACI); B cell maturation antigen Background: A composite[power Doppler/greyscale US [PDUS)] (BCMA)]. BAFF-R is expressed on all B cells. Binding of BAFF to synovitis score, developed by the OMERACT–EULAR–Ultrasound BAFF-R is essential for B cell survival and maturation. TACI expression Task Force, was shown to be responsive in RA patients with is induced after B cell activation. Binding of BAFF to TACI may have inadequate response to MTX who were treated with abatacept inhibitory effects on B cell survival and proliferation (shown in (ABA); a rapid parallel change in PDUS and DAS for 28 joints mouse models and some rare human diseases). The objective (DAS28) was demonstrated. Data from clinical studies that have of this study was to test the hypothesis that BAFF and APRIL utilized PDUS indicate that it could be useful in monitoring RA promote B cell repopulation after rituximab and predict clinical treatment effects; however, discordant correlations have been found response in RA. between ultrasound scores and clinical outcomes measured at Methods: 73 patients with active RA (DAS for 28 joints >3.2) despite the same time point. In this secondary analysis of the APPRAISE MTX received 2 1000 mg rituximab. Clinical response was categor- study, we explored correlations between changes in PDUS and clinical ized by EULAR criteria; serum BAFF and APRIL were measured using scores. ELISA; B cell naive (CD19þCD27), memory CD19þCD27CD38) and Methods: Individual joint PDUS scores were combined in the Global plasmablast (CD19þ/-CD27þþCD38þþ) subsets were measured by OMERACT-EULAR Synovitis Score (GLOESS) of metacarpophalan- flow cytometry. In 13 patients, expression of BAFF receptors (BAFF-R, geal joints 2–5 (primary objective), reduced joint set (9 paired) and all TACI and BCMA) was also measured by flow cytometry. examined joints (22 paired). Correlation between changes in GLOESS Results: There was a significant increase in serum BAFF at all time and clinical scores were assessed through: effect size, expressed as points after rituximab (P < 0.05), and a significant reduction in APRIL standardized response means of GLOESS and mean changes in (P < 0.05). Six months after rituximab, BAFF-R reduced significantly DAS28 from baseline to weeks 1, 12 and 24; Pearson’s correlation (P ¼ 0.0002) on naive B cells (consistent with the emergence of BAFF-R coefficient, for assessing correlation between early and late changes in negative immature B cells from bone marrow), while TACI increased DAS28, and early and late changes in all GLOESS scores; and significantly on memory B cells (P ¼ 0.0001) and plasmablasts Spearman’s correlation coefficient, for assessing correlation between (P ¼ 0.001; consistent with their being recently differentiated). Six early changes in GLOESS and lower levels of synovitis at week 24. months after rituximab, there was no relationship between BAFF and Furthermore, the relationship between GLOESS and clinical response total or naive B cells (the largest subpopulation) (R ¼ –0.270, P ¼ 0.29). was explored by analysing the correlation between changes from However, there was a weak negative correlation between BAFF and baseline in the number of tender and swollen joints and matched joint memoryBcells(R¼ –0.550, P ¼ 0.022) and a strong negative GLOESS. correlation between BAFF and plasmablasts [R ¼ –0.817, P < 0.001). Results: No significant correlations were found between: changes Patients with moderate or good EULAR response at 6 months had from baseline in DAS28 and GLOESS, or component scores (synovial significantly higher serum BAFF at baseline (P ¼ 0.033)] and at 6 months hypertrophy, PD, joint effusion) at any time point; or between early (P ¼ 0.029). (baseline to weeks 1, 2 or 4) changes in GLOESS, or components, and Conclusion: After rituximab there is no relationship between BAFF changes in the sum of swollen joints from baseline to weeks 12 or 24. and overall B cell return, but a negative correlation between serum Within the assessment method, i.e. between clinical scores, or BAFF and plasmablasts. These data may be explained by the effect of between GLOESS at different time points, moderate-to-high correla- supra-physiological serum BAFF titres binding to memory B cells via tions were found between early (to week 12) and late (week 24) their increased expression of the inducible, inhibitory TACI receptor. improvements in DAS28, and similarly between changes in GLOESS These results suggest that in some circumstances BAFF may, in fact, (any joint set): Pearson’s coefficient range 0.37–0.71. Only changes in be inhibitory to B cell differentiation. These results may be important GLOESS at week 12 were able to differentiate between early versus for understanding the clinical effects of B cell depletion (effective in late clinical responders. RA), as well as BAFF-blocking biologics (not effective in RA). Conclusion: PDUS is a responsive measure of joint activity in patients Disclosure statement: F.P. has received research funding from starting abatacept, but the extent of PDUS response does not Roche. P.E. has received consulting fees from BMS, Abbott, Pfizer, correlate with extent of clinical response. This suggests that PDUS MSD, Roche and UCB; has received honoraria from Roche and adds independent information on response to treatment which needs Chugai; and has received research grants from Abbott, BMS, Pfizer, to be explored further. This study was supported by Bristol-Myers MSD and Roche. E.M.V. has received consulting fees from GSK; has Squibb. received honoraria from Roche and Chugai; and has received research Disclosure statement: M.A.D. has served on speakers’ bureaus grants from Roche and Sandoz. All other authors have declared no on behalf of BMS, AbbVie. M.B. has received consulting fees conflicts of interest. from BMS. H.B.H. has received honoraria from AbbVie, Roche, i82 Tuesday 28 April 2015 POSTER VIEWING I

Pfizer, BMS and UCB; and has received research grants from AbbVie, Roche and Pfizer. P.B. has received consulting fees from AbbVie, Egis, MSD, Philips, Pfizer and Richter; has served on RHEUMATOID ARTHRITIS: CLINICAL speakers’ bureaus on behalf of AbbVie, BMS, GE, Janssen, MSD, FEATURES Philips, Pfizer, Richter and UCB; and has received research grants from AbbVie, ESAOTE and Roche. I.M. has received consulting fees from Bioiberica Pharma, AbbVie, GE and ESAOTE. E.N. has received consulting fees from AbbVie, Roche Pharma, 081. RADIOGRAPHIC PROGRESSION RATES OVER THE BMS, Pfizer, UCB, General Electric and Esaote; and has FIRST 10 YEARS IN PATIENTS WITH EARLY RHEUMATOID received research funding from MSD. M.Ø. has received consulting ARTHRITIS: A SYSTEMATIC REVIEW fees from Abbott/AbbVie, BMS, Boehringer-Ingelheim, Eli Lilly, Centocor, GSK, Janssen, Merck, Mundipharma, Novo, Pfizer, Lewis Carpenter1, Rachel Sharpe1, Elena Nikiphorou2,3, Schering-Plough, Roche, UCB and Wyeth; and has received Sam Norton4, Frances Bunn5, David L. Scott6 and Adam Young2,3 research grants from Abbott/AbbVie, Centocor, Merck and 1Centre for Lifespan & Chronic Illness Research Centre, University of Schering-Plough. C.G. is a shareholder of BMS and Novartis; and Hertfordshire, Hatfield, 2ERAS & ERAN, St Albans City Hospital, St is an employee of Novartis Pharma AG. M.L.B. is an employee Albans, 3School of Life & Medical Sciences, University of and shareholder of BMS. All other authors have declared no Hertfordshire, Hatfield, 4Psychology Department, Institute of conflicts of interest. Psychiatry, King’s College London, London, 5Centre for Research in Primary & Community Care, University of Hertfordshire, Hatfield and 6 080. CAN CREATINE SUPPLEMENTATION IMPROVE BODY Rheumatology, King’s College Hospital, London, UK COMPOSITION AND OBJECTIVE PHYSICAL FUNCTION IN RHEUMATOID ARTHRITIS PATIENTS? A RANDOMIZED Background: Long-term radiographic progression is an important CONTROLLED TRIAL outcome measure in RA. The presence of erosions and joint space narrowing can mark the failure or success of a treatment. Thomas J. Wilkinson1, Andrew B. Lemmey1, Fazal Sheikh2, Understanding the natural course of the disease, and the way in Yasmeen Ahmad2, Sarang Chitale2, Jeremy Jones1,2, which radiographic damage progresses over time, is fundamental in Peter Maddison1 and Thomas D. O’Brien1 improving the clinical management of RA. Using data from published, 1School of Sport, Health and Exercise Sciences, Bangor University, longitudinal cohort studies on patients with early RA, this meta- Bangor and 2Peter Maddison Rheumatology Centre, Betsi Cadwaladr analysis aims to update a review conducted in 2003 on radiographic University Health Board, Llandudno Hospital, Llandudno, UK progression (n ¼ 7), and provide a summary of the overall progression rates of radiographic damage over the first 10 years of disease. Background: RA is characterized by muscle wasting (rheumatoid Methods: Publications were identified by computerized searches of cachexia), which contributes to substantial reductions in strength and PubMed, Cochrane Library (including CENTRAL, CDSR, DARE and impaired physical function. Current DMARD and biologic therapy fail to HTA) and Scopus. All databases were searched from inception to 31 restore muscle mass or reduce fat mass. In healthy individuals, oral February 2014. Studies had to fulfil the following inclusion criteria for creatine (Cr) supplementation has been shown to increase lean mass meta-analysis: observational cohort studies; long-term data (>5 years) (LM) by stimulating muscle protein synthesis, and to improve and patients with early RA (<3 years from symptom onset to first visit). performance via the augmented LM and enhanced production of The sample size, mean and S.D. of either the Larsen or total Sharp ATP (i.e. energy). The objective of this double-blind randomized score for radiographic damage was recorded at all available follow-up control trial was to investigate whether Cr supplementation has similar time points. These estimates were then meta-analytically modelled benefits in RA patients. using an inverse variance weighted least squares regression to Methods: Forty RA patients with stable disease underwent 12 estimate annual progression rates for both scoring methods. weeks oral supplementation of either Cr [n ¼ 18, 12 females, 62.3 Results: A total of 2618 publications were identified in the literature (10.5) years] or placebo [n ¼ 22, 15 females, 58.1 (10.6) years]. For search. Of these, 28 studies were eligible for inclusion into the meta- those randomized to Cr, a 5-day loading phase of 20 g Cr (4 5 g)/ analysis. Ten of these studies provided sufficient data for the analysis. day was followed by a maintenance dose of 3 g/day for the Three studies reported Larsen scores, while seven studies reported remainder of the supplementation period. The placebo was a Sharp scores. The meta-analysis indicated an annual rate of 2.6 (95% glucose drink with similar flavouring and colouring to the Cr mixture. CI 2.3, 2.9) Larsen units per year and 6.1 (95% CI 5.8, 6.4) Sharp units Body composition (total and regional LM and fat mass) was per year over the 10-year follow-up period. This represents a change estimated by DXA, with appendicular LM (ALM; the summed LM of 1.3% of maximum damage per year for both scoring methods. The of the arms and legs) used as a surrogate measure of total muscle models indicate that the Larsen exhibits a linear rate of progression mass. Intracellular (ICW) and extracellular water (ECW) was over 10 years, whereas the Sharp score progresses more rapidly, with determined by bioelectrical impedance spectroscopy. Objective the rate of damage accelerating each year. physical function was assessed by sit-to- stand in 30 s (STS-30), Conclusion: This review provides precise estimates of radiographic 8-foot-up-and-go (UG), 50-foot-walk (50 W), handgrip strength (HGS) progression over the first 10 years of disease for patients with early RA. and isometric knee extensor strength (IKES). All assessments were The review found relatively few publications on the long-term (>5 year) performed at baseline (pre-supplementation), week 12 (post-supple- progression of radiographic damage in RA. Compared with figures mentation) and week 24 (12 weeks post-supplementation). Data was reported previously, the annual progression rate for Larsen scores was analysed using repeated measures ANOVA and is presented as lower (3.8 vs. 2.6), while the annual progression rate for total Sharp means (S.D.). scores was higher (4.3 vs. 6.1). This highlights the differences in Results: Twelve weeks of Cr supplementation increased ALM [0.48 radiographic scoring methods and the potential pitfalls in comparing (0.13) kg, P ¼ 0.002] and total LM [0.57 0.27 kg, P ¼ 0.049] without studies that use different radiographic scoring methods. The influence increasing fat mass [0.38 (0.37) kg, P ¼ 0.321]. The DXA changes in LM of potential confounding factors on these rates of progression will be were corroborated by increases in ICW [0.56 (0.17) l, P ¼ 0.005, examined. r ¼ 0.556, P ¼ 0.032]. No body composition changes were seen in the Disclosure statement: The authors have declared no conflicts of placebo group. IKES [n ¼ 41.8 (13.6), þ13.0%, P ¼ 0.009] and HGS interest. [n ¼ 19.4 (9.0), þ7.6%, P ¼ 0.051] were both increased, and subse- quently maintained 12 weeks after supplementation had ceased, in the Cr group. No change in these strength measures occurred in the 082. ULTRASOUND FINDINGS IN FIBROMYALGIC placebo group. No change in the physical function measures: STS30, RHEUMATOID ARTHRITIS: A PILOT CROSS-SECTIONAL UG or 50 W were observed in either group. Similarly, disease activity STUDY (DAS for 28 joints) remained unchanged throughout the trial in both Khaldoun Chaabo1, Aneela Mian1, Bruce Kirkham1 and groups. Toby Garrood1 Conclusion: Oral Cr supplementation significantly enhanced muscle 1Rheumatology Department, Guy’s and St Thomas’ NHS Foundation mass and strength in RA patients. No treatment-related adverse side Trust, London, UK effects were reported, suggesting that Cr supplementation is a safe, widely acceptable, cheap and reasonably effective adjunct treatment Background: FM can be present as a comorbid condition in up to for rheumatoid cachexia. 20% of patients with RA. The presence of FM can complicate Disclosure statement: The authors have declared no conflicts of treatment decisions as DAS can be high despite limited clinical interest. evidence of active inflammation. Recent work has suggested that POSTER VIEWING I Tuesday 28 April 2015 i83

patients who have more tender than swollen joints out of 28 [tender surprisingly the two methods do not closely correlate except in the joint count (TJC) minus tender joint count (SJC), with a difference of at severest DAS28 group. The importance of these findings is in the least 7, are significantly more likely to have comorbid FM [fibromyalgic reminder of the physical impact on function that current or previous RA (FMRA)], as defined by the 1990 ACR FM classification criteria disease has on patients. Overemphasis on disease activity assess- (sensitivity and specificity 72–83% and 80–98%, respectively). ment may obscure significant disabilities in patients. Modern practice Ultrasound can detect subclinical inflammation in inflammatory emphasizes the systematic early detection and intense treatment of arthritis. The aim of this study was to determine whether patients active disease. These findings suggest the need to adopt a similar meeting the above definition of FMRA had significantly less joint integrated approach to identify the rehabilitation needs of patients with inflammation on ultrasound. established disease and the need to identify appropriate outcomes or Methods: RA patients with DAS for 28 joints scores >2.6 were targets. recruited to two groups meeting or not meeting the FMRA criteria Disclosure statement: The author has declared no conflicts of (TJCSJC at least 7). Patients completed questionnaires including interest. PHQ9 (depression), GAD7 (anxiety), PHQ15 (somatization), FACIT- fatigue, HAQ, global health assessment VAS and the Widespread Pain 084. RHEUMATOID ARTHRITIS AND CHRONIC FATIGUE Index (WPI). The TJC, SJC, Symptom Severity Score (SSS) and the number of fibromyalgia soft-tissue tender points were recorded by the Jamie Hewitt1 and Laura Wetherly1 physician. WPI and SSS are the components of the 2010 ACR 1Government Affairs, National Rheumatoid Arthritis Society, preliminary diagnostic criteria for FM. Patients underwent ultrasound Maidenhead, UK scan by a second blinded physician of the wrists, MCPJs and PIPJs bilaterally. Grey-scale (GSUS) and power Doppler (PDUS) scores were Background: Chronic fatigue is a symptom of RA that can severely recorded for each joint (scale 0–3). Differences between groups were impact patients’ quality of life, including ability to work. However, tested for significance using the Mann–Whitney U test and categorical clinical guidelines in the UK contain few references to the effective differences were determined by Fisher’s exact test. Significance was management of chronic fatigue. To quantify the impact and under- set at P < 0.05. stand how it is managed, the National Rheumatoid Arthritis Society Results: 26 and 21 patients were recruited to the FMRA and non- (NRAS) surveyed over 2000 people with RA about their experiences. FMRA groups, respectively. FMRA patients were significantly more Methods: NRAS developed open and closed survey questions to likely to meet the 1990 ACR classification criteria for FM (P ¼ 0.0002) explore different impacts of chronic fatigue. To facilitate comparison, but not the 2010 preliminary diagnostic criteria. DAS scores were validated questionnaires were used for: Bristol Rheumatoid Arthritis higher in the FMRA group (4.98 vs 4.08, P ¼ 0.003). Patients with Fatigue Multidimensional Questionnaire; Bristol Rheumatoid Arthritis FMRA had significantly lower total GSUS scores (P ¼ 0.036); differ- Fatigue – Numerical Rating Scales; Work Productivity and Activity ences in total PDUS scores were not statistically significant. Impairment Questionnaire; and Work Activity Limitations Scale. 5212 Significantly higher levels of fatigue (P ¼ 0.003), depression (0.015), invitations were sent out electronically to people with RA and somatic symptoms (0.003) and HAQ (0.027) were seen in the FMRA distributed via e-newsletters and social media. 2029 respondents group. No significant differences were seen for ESR, global health, completed the survey, a further 716 clicked the link but failed to SSS, WPI or anxiety. complete it, and 36 did not meet the qualifying criteria of being over 18, Conclusion: Patients with FMRA as defined by the TJCSJC criteria resident in the UK and diagnosed with RA. did not have significantly less active disease as defined by total PD Results: Chronic fatigue is widespread: 89% of respondents scores in our cohort although there was a difference in total GS scores. experienced it and 98% of these said it affected them during the This suggests that patients may continue to have subclinical disease previous 7 days. Chronic fatigue significantly affects work: 71% of despite the presence of comorbid FM which may require escalation of working age respondents that were unemployed said it contributed to treatment. It is not known whether such patients can be differentiated them not being able to work and 24% said they changed jobs because by clinical criteria or whether imaging is required to stratify for disease of it. Employers need to help more: 23% of employed respondents activity. This question is the subject of ongoing work. took more than 10 days off in the last 12 months due to chronic fatigue, Disclosure statement: The authors have declared no conflicts of but 49% said their line manager had not discussed or offered changes interest. in the workplace. Chronic fatigue has a high impact on mental health: 90% of respondents said it caused them to feel down or depressed during the last 7 days, including 38% who said they felt very down or 083. APPLICATION OF RAPID3 ALONGSIDE DAS28 IN depressed. Chronic fatigue has a high impact on relationships: 70% of OUTPATIENT PRACTICE: IS FUNCTIONALITY THE respondents said it prevented them from taking part in family activities FORGOTTEN ELEMENT OF PATIENT ASSESSMENT? and 54% said it negatively affected their sex life. Chronic fatigue is not John N. Fordham1 well managed by healthcare professionals: 66% of respondents had 1Rheumatology, James Cook University Hospital, Middlesbrough, UK never or rarely been asked about it; and 79% said it had never been measured. RA patients need to access treatments for chronic fatigue: Background: Although disease activity assessment is accepted as an 16% of respondents said they did nothing to manage it and only 2% essential component of patient management programmes in the had attended a chronic fatigue self-management programme. context of DMARD use with the aim to reduce disease activity and, Conclusion: The results suggest chronic fatigue has wide-ranging ultimately, the risk of disability in newly presenting patients, less impacts, but is poorly managed by healthcare professionals and RA attention may be given to the functional assessment of patients with patients. Clinical guidelines should be revised to prioritize its effective longstanding disease. RAPID3 is a validated tool which, unlike DAS for management, including use of validated fatigue measures. Patient 28 joints (DAS28), has pain as well as specific functional components. education and self-management strategies should also be prioritized It derives from a subset of variables from the multidimensional HAQ. for RA patients. Finally, more should be done to raise awareness of The purpose of this study was to compare both tools alongside each chronic fatigue among employers and how to manage it in the other in the setting of general rheumatology clinics. workplace. Methods: Both DAS28 and RAPID3 assessments were carried out by Disclosure statement: The authors have declared no conflicts of the same clinician on consecutive patients with RA attending a general interest. rheumatology clinic including newly diagnosed and established case of rate study period was over a period of 2 months. 085. FATIGUE AND FUNCTIONAL DISABILITY IN Results: 42 patients had both assessments carried out. The average RHEUMATOID ARTHRITIS: EVIDENCE FOR A COGNITIVE age was 56.6 years (35–84), 27 were female .Respectively, 12%, 12%, BEHAVIOURAL MODEL 29% and 48% were in the near remission, low, moderate and severe 1 2 3 2 categories of physical function. This compared with DAS28 categories Katherine Irving , Faith Matcham , Sheila Ali and Trudie Chalder 1 2 of 27%, 15%, 37% and 21% for remission, low, moderate and severe. Rheumatology, King’s College Hospital, Department of Comparison of the two indices revealed a correlation coefficient of Psychological Medicine, King’s College London, Institute of 0.505.Further analysis showed that complete agreement between the Psychiatry, Psychology and Neuroscience and 3Chronic Fatigue two measures occurred with the DAS28 severe group which were also Research and Treatment Unit, South London and the Maudsley NHS found to be in the highest physical disability category. Conversely Foundation Trust, London, UK however analysis of the severe RAPID3 group showed the impact on function was under estimated by DAS28. Background: Despite progress in the medical treatment of RA, fatigue Conclusion: This study has revealed high prevalence of significant and functional disability remain significant problems for patients and functional disability in patient attending general rheumatology clinics. are not directly related to disease activity. Studies have shown Over three-quarters were in the moderate or severe group. This may associations with mood, particularly with depression, but illness reflect the age group and hence longevity of disease in this group. Not related beliefs and coping mechanisms are also likely to be important. i84 Tuesday 28 April 2015 POSTER VIEWING I

A cognitive behavioural model based on the fear avoidance model has management of neuropsychiatric disorders in RA patients may greatly been used to explain the development of fatigue and disability in improve the patients’ health related quality of life. chronic fatigue syndrome and in other medical conditions but evidence Disclosure statement: The authors have declared no conflicts of is lacking to support this model in RA. The aim of this study was to interest. explore whether unhelpful cognitions and behaviours, such as catastrophizing, symptom focussing and fear avoidance are asso- 087. PSYCHOLOGICAL CORRELATES AND PREDICTORS OF ciated with fatigue and functional disability in patients with RA. FATIGUE IN RHEUMATOID ARTHRITIS: A SYSTEMATIC Methods: Patients attending the Rheumatology Outpatient Clinic REVIEW completed a questionnaire pack including the Chalder Fatigue Scale (CFS), Work and Social Adjustment Scale (WSAS), HAQ, Hospital Faith Matcham1, Sheila Ali2, Matthew Hotopf1 and Trudie Chalder1 Anxiety and Depression Scale (HADS) and Cognitive and Behavioural 1Department of Psychological Medicine and 2Chronic Fatigue Responses to Symptoms Questionnaire (CBRQ). Demographic and Research and Treatment Unit, Institute of Psychiatry, King’s College disease related data were collected from hospital records. Multiple London, London, UK regression models were created, with fatigue, HAQ, DAS and WSAS as dependent variables and cognitive behavioural responses as Background: Fatigue is common and debilitating in RA. The limited independent variables. These models were adjusted for age, disease efficacy of biotherapies to reduce fatigue has resulted in a greater duration, ESR and psychological distress, using the total HADS score. focus on psychological variables. The purpose of this review was to Results: Data were obtained for 56 patients fulfilling the 1987 ACR systematically identify psychological variables related to fatigue in RA, and/or 2010 ACR/EULAR criteria for a diagnosis of RA. 45 (80.4%) with the overall aim of suggesting evidence-based targets for fatigue were female with median age 53.7 years (S.D. 13.4) and median disease intervention. duration 10.2 years (S.D. 9.3). Fatigue was associated with increased Methods: Electronic databases were systematically searched from fear avoidance (b ¼ 0.44, S.E. ¼ 0.18, d ¼ 0.35, P ¼ 0.02), catastrophiz- inception to March 2013. Inclusion criteria were: observational design ing (b ¼ 0.54, S.E. ¼ 0.25, d ¼ 0.34, P ¼ 0.04), embarrassment avoid- or baseline data from a trial; published quantitative studies; reported ance (b ¼ 0.44, SE ¼ 0.16, d ¼ 0.36, P ¼ 0.01) and symptom focussing results for RA separately from other rheumatological conditions. (b ¼ 0.48, S.E. ¼ 0.20, d ¼ 0.40, P ¼ 0.02). Higher levels of disability in Studies were excluded if they used qualitative, case series, case work and social domains were associated with increased fear reports, expert opinion or consensus statements; used a selective avoidance (b ¼ 0.97, S.E. ¼ 0.36, d ¼ 0.42, P ¼ 0.01) and behavioural sample (e.g. intervention trials); did not use published/appropriate and avoidance (b ¼ 1.13, SE ¼ 0.35, d ¼ 0.49, P < 0.01). HAQ scores were replicable measures to assess psychological factors and fatigue; and not associated with any cognitive behavioural responses. recruited patients with self-reported RA diagnosis. The heterogeneity Conclusion: This study shows that unhelpful cognitions and beha- of the included studies and broad nature of the review aim precluded viours, particularly fear and avoidance, are associated with fatigue and meta-analysis, therefore a narrative synthesis was performed. work and social disability in RA but not with HAQ. Cognitive However where reported, we compared effect sizes between behavioural therapy (CBT) has been shown to be effective in improving psychological variables and biomarkers of disease severity to examine fatigue and function in RA and this study provides further support for the driving factors associated with fatigue in these patients. the use of CBT to modify thoughts and behaviours, particularly Results: Twenty-nine studies met inclusion criteria and were included surrounding fear and avoidance. in the narrative synthesis. A wide range of psychological variables Disclosure statement: F.M. and T.C. receive salary support from the were addressed, spanning six categories: affect and common mental NIHR. All other authors have declared no conflicts of interest. disorders; RA-related cognitions; non-RA-related cognitions; person- ality traits; stress and coping; and social support/interpersonal relationships. The majority of studies examined affect and common 086. CLINICAL AND SUBCLINICAL NEUROPSYCHIATRIC mental disorders, with most finding significant associations between ABNORMALITIES IN RHEUMATOID ARTHRITIS PATIENTS worsening mood and increased fatigue. Several studies examined RA- Eman M. Khedr1, Noha Abo El Fetoh1, Omar Omar Herdan2, related cognitions such as disease self-efficacy, illness perceptions Dina H. El-Hammady3, Hosam Khalifa1, Rania M Gamal3 and and beliefs about medications. Again, the majority of studies found Anwar Anwar M. Ali1 significant associations between these cognitions and fatigue levels. 1Neurology and Psychiatry Department, 2Rheumatology Unit, Six non-RA-cognitions were examined, with mixed findings: whereas Department of Internal Medicine and 3Rheumatology and goal ownership, fatigue self-efficacy and social mobilization self- Rehabilitation Department, Assiut University Hospital, 71515 Assiut, efficacy were found to be associated with fatigue, role satisfaction was Egypt not and there was mixed evidence for fatigue causal attributions and fatigue catastrophizing. Seven studies examined the personality traits Background: RA is a chronic, systemic, inflammatory disease with with most results finding no support for a relationship between these probable autoimmune aetiology. RA has many secondary complica- traits and fatigue. Similarly, limited support was found for the tions and a variety of neuropsychological consequences. The aim of relationship between stress and coping and fatigue, or social the study was to estimate the frequencies of neuropsychiatric support and fatigue. In the 13 studies that looked at both disease disorders in RA patients and their relation with the duration and and psychological variables, effect sizes were comparable in activity of disease. 5 (38.5%). Psychological variables were more strongly associated Methods: Seventy-four consecutive female, RA patients were in 7 (53.8%), and disease variables were more strongly associated in recruited and compared with 25 age and educational status-matched 1 (7.7%). female healthy volunteers. All eligible participants underwent clinical, Conclusion: Associations between mental health and RA-related laboratory and electrophysiological examinations (motor and sensory cognitions and fatigue were fairly consistent, and sustained after nerve conduction study, F-wave of four limbs, P300 Event related adjustment for markers of disease severity. The results of this review Potential (ERP) and electroencephalography (EEG). Structured Clinical suggest that interventions for fatigue in RA may benefit from an Interview for Diagnostic and Statistical Manual of Mental Disorders 3rd integrated focus on mental health and RA-related cognitions in edition, Revised (DSM-III-R) Axis I Disorders (SCID-I) for diagnosis of addition to established RA pharmacological treatment. psychiatric illness and Wechsler Adult Intelligence scale 3rd edition Disclosure statement: The authors have declared no conflicts of (WAIS-III) with assessment of total scale, verbal and performance interest. intelligence quotients (IQ)were administered to all participants. Results: Fourteen patients (18.9%) had evidence of symptomatic 088. HOW MUCH DOES FATIGUE CONTRIBUTE TO THE peripheral neuropathy and radiculopathy, while 60.8% had psychiatric PHYSICIAN GLOBAL ESTIMATES IN DIFFERENT RHEUMATIC disorders. Depression was the most prevalent psychiatric disorder DISEASES? DATA FROM ROUTINE CARE ON A (45%), followed by anxiety (27%) and comorbid anxiety with MULTIDIMENSIONAL HEALTH ASSESSMENT depression (21.6%). low IQ score was recorded in 54%. P300 latency QUESTIONNAIRE was significantly prolonged (P ¼ 0.0001) and seven (9.5%) RA patients recorded abnormal P300 latency (>mean 2SD) compared with Theodore Pincus1, Elena Nikiphorou2, Annie Huang1 and control values. Abnormal EEG findings were observed in 48.6%. VAS Isabel Castrejon1 pain score was significantly higher among patients with psychiatric 1Rheumatology Department, Rush University Medical Center, disorders versus patients without psychiatric disorders (P ¼ 0.0001). Chicago, IL, USA and 2Rheumatology Department, Addenbrooke’s Significant negative correlation was recorded between DAS and total Hospital, Cambridge, UK IQ (P ¼ 0.01), while no significant association between with the DAS with the presence of neuropathy or psychiatric disorders. Background: Fatigue is controversial in the rheumatology literature Conclusion: Cognitive impairment, depression, anxiety and peripheral regarding how much it may contribute to disease burden in different neuropathy are common in RA patients. Early diagnosis and rheumatic diseases. A multidimensional HAQ (MDHAQ) designed for POSTER VIEWING I Tuesday 28 April 2015 i85

routine care includes a 0–10 fatigue visual analogue scale (VAS), which were included for this study. There was no significant correlation allows comparison with other clinical measures in patients with between the individual health indices and medication used. A paired different rheumatic diseases. t-test was also used to compare the groups for EQ 5D score and Methods: All patients seen in routine care at one academic clinical anxiety/depression score separately with no significant values. setting complete a 2-page MDHAQ in 5–10 min in the waiting area, Conclusion: In this study, we have tried to assess, the difference in prior to seeing the rheumatologist. The MDHAQ includes a 0–10 scale the quality of life, as measured by EQ 5D in 2 similar cohorts receiving for physical function in 10 activities, three 0–10 VAS for pain (PN), either biologic or non-biologic DMARD. There was no significant patient global estimate (PATGL), and fatigue (FT), and queries relationship between either group with any of the five health concerning sleep quality, anxiety and depression. RAPID 3 (0–30) is dimensions recorded as part of the EuroQol. Quality of life is similar the sum of three 0–10 scores for FN, PN and PATGL. A physician in Low DAS- RA patients with no added benefit with regards to either global estimate (DOCGL) is completed as a 0–10 VAS. Three separate of the treatment group. multivariate regression analyses were performed in patients with RA, Disclosure statement: The authors have declared no conflicts of SLE, or OA, to recognize possible explanatory variables for DOCGL, as interest. the dependent variable, among fatigue, RAPID3, and patient report of anxiety (correlated at higher levels with DOCGL than depression) as 089 TABLE 1. Summary of patient characteristics independent variables. Results: The study included 50 patients with RA, 66 with SLE, and 57 Medication Age, mean Duration of Modified DAS, EQ 5D, with OA. Mean VAS fatigue levels were 4.6 in RA, 4.4 in SLE, and 5.2 in (range), years RA, mean HAQ, mean mean mean OA (P ¼ 0.39). Mean DOCGL was 3.9 for RA, 2.9 for SLE and 4.5 for OA (range), years (P < 0.001). In patients with RA, the overall R2 for the regression model Non-biologic 59.2 (44–77) 59.2 (44–77) 1.25 2.94 0.60 was 0.65, indicating that 65% of the variation in physician global DMARD estimate was explained by the three independent variables: fatigue, Biologic 59 (41–74) 13.9 (4–34) 1.39 2.92 0.50 RAPID3 and anxiety (Table 1). The only significant explanatory variable was RAPID3. In SLE, R2 was 0.32; fatigue was the only significant explanatory variable. In OA, R2 was 0.65; both RAPID3 and anxiety, but not fatigue, were significant explanatory variables. Conclusion: Fatigue is significant to explain physician global estimate RHEUMATOID ARTHRITIS: in the SLE group, but not in the RA or OA groups. Fatigue may reflect both inflammatory and non-inflammatory mechanisms in different COMORBIDITIES individual patients with various rheumatic diseases. Disclosure statement: The authors have declared no conflicts of interest. 090. COMORBIDITIES AND TREATMENT INTENSITY IN RHEUMATOID ARTHRITIS 088 TABLE 1. Regression models with explanatory power in variation of DOCGL 1 2 3 3 RA (n ¼ 50) SLE (n ¼ 66) OA (n ¼ 57) Sardar Bahadur , Aneela N. Mian , Ian Scott , James Galloway , Louise Pollard1, Gabrielle H. Kingsley3 and David L. Scott3 1 b coefficient P-value b coefficient P-value b coefficient P-value Rheumatology, Lewisham and Greenwich NHS Trust, 2 3 Fatigue (0–10) 0.11 0.55 0.75 0.02 –0.007 0.99 Rheumatology, King’s College Hospital and Rheumatology, King’s RAPID3 (0–30) 0.75 <0.001 –0.78 0.55 0.45 0.01 College London, London, UK Anxiety (0–3) –0.09 0.49 –0.08 0.61 0.44 <0.01 R2 0.65 <0.001 0.32 <0.01 0.65 <0.001 Background: Many patients with RA continue to have incompletely controlled disease. Not all patients receive maximal treatment with DMARDs. One potential reason for poor control and submaximal treatment is that comorbidities limit treatment intensity. We have 089. COMPARING QUALITY OF LIFE IN LOW DISEASE evaluated this possibility by comparing two clinical cohorts of RA ACTIVITY: RHEUMATOID ARTHRITIS PATIENTS, RECEIVING patients to investigate comorbidities and treatment intensity. BIOLOGICS AND COMBINATION DMARD Methods: We prospectively evaluated disease activity [DAS for 28 joints (DAS28) scores], treatment intensity and treatment increases 1 1 1 Leena Yalakki Jagadeesh , Cassandra Hong and Bruce Kirkham with DMARDs, biologics and steroids in two RA cohorts assessed in 1 Rheumatology, Guy’s and St Thomas’ NHS Foundation Trust, 2009–10 and 2014 attending the same outpatient clinics. We also London, UK evaluated the potential impact of comorbidities in treatment decisions in the second cohort. Background: RA is the most frequent inflammatory rheumatic Results: In the 2009–2010, cohort 127/304 (42%) had intermediate disease, associated with deformities and joint destruction. Patients DAS28 scores (3.2–5.1) and 63 (21%) had high DAS28 scores (>5.1). with active RA have shown to suffer deficits in health quality, along In the 2014 cohort, 79/220 (36%) had intermediate and 33 (15%) high with a number of physical functioning and mental health dimensions. scores. Treatment intensity had gradually increased. In 2009–2010, 62/ The impact of a disease on patients’ quality of life is measured using 304 (20%) patients had no suppressive therapy, 65 (22%) were taking health indices. In RA, disease activity is measured using DAS, and a combination DMARDs and 47 (15%) were taking biologics. In the 2014 number of health indices have been used to measure the quality of life. cohort, 12/220 (6%) had no suppressive therapy, 86 (29%) were taking The EuroQol (EQ 5D) is one such health index capturing five health combination DMARDs and 55 (25%) were taking biologics. Treatment dimensions (mobility, self-care, usual activity, pain/discomfort and was increased in 88/304 (34%) patients in the 2009–2010 cohort, and anxiety /depression), with three categories to each dimension: no 66/220 (30%) of patients in 2014 cohort including 76% and 73% problems, moderate problems and extreme problems. Our objective respectively of patients with active RA. 154/220 (82%) patients was to compare the quality of life, as measured by EQ-5D in RA, with had one or more comorbidities; in 88/220 (40%) there was a low DAS patients receiving biologic and combination DMARD. comorbidity involving major non-musculoskeletal system (cardiac, Methods: Cross-sectional longitudinal data from RA patient database chest, mental health, renal, gastrointestinal, cancer). 51/180 attending a tertiary centre during 2013 were analysed. As a routine (28%) with any comorbidity and 39/88 (33%) with a major non- clinical practice, the following data is collected and updated on our RA musculoskeletal comorbidity increased treatment. There was no centre database: HAQ, EQ 5D, pain thermometer and DAS28.The evidence patients with comorbidities reduced the likelihood of database also has a record of laboratory measures and medication increasing treatment. exposure. Patients were matched based on their age, sex and disease Conclusion: Disease control is gradually improving over time with duration. Spearman partial correlation and paired t-test was used to treatment intensities increasing. Although not all patients with active compare quality of life measures against medication exposure. disease receive more treatment when assessed, the presence of Results: Data from 127 RA patients with low DAS were reviewed. 47 comorbidities is not a limiting factor in treatment decisions. The patients were excluded due to data unavailable with regards to EQ 5D reasons why not all patients receive maximal treatment remain and disease duration. Of the 80 patients, 51 patients (63.7%) were on undefined. combination DMARDs and the remaining 29 (36.3%) were on anti-TNF Disclosure statement: The authors have declared no conflicts of (Table 1). Having matched the data based on age (3 years), sex and interest. disease duration (2 years), a total of 34 patients (17 in each group) i86 Tuesday 28 April 2015 POSTER VIEWING I

091. ARE CARDIAC RISK PROFILES OF EARLY defined as those resulting in hospitalization for more than 24h, flares RHEUMATOID ARTHRITIS PATIENTS ADDRESSED AT requiring i.v. therapy, malignancies, life-threatening events or death. CLINIC? Results: 53 patients with ILD were identified from a cohort of 576. 19 were male and 34 female; median age 63.4 years [interquartile range Tanja Harrison1, Cheryl Barnabe1 and Liam Martin1 1 (IQR) 58–72]; median RA duration 9.3 years (IQR 8–12); median ILD Medicine, University of Calgary, Calgary, AB, Canada duration 5 years (IQR 3–7) at baseline. Total follow up was 171 patient- years. There was no substantive or significant reduction in FVC and Background: RA patients have higher cardiovascular disease (CVD) DLCO over time; all p > 0.1. 9 patients received CYC (CYC) prior to risk scores compared with the general population. It has been reported rituximab: 6 had stable ILD during rituximab treatment while 3 required that rheumatologist feel CVD risk management is the responsibility of further CYC due to ILD progression. 2 patients who had not previously primary care providers (PCP). This situation creates a serious care gap received prior CYC required CYC treatment due to worsening ILD after as the CVD risk/management is left to the patients’ PCP who may not rituximab. Only three patients (0.5%) were diagnosed with new ILD be comfortable managing these clinical issues in complex patients. after rituximab. 78 SAEs were recorded in 33 patients: 72 were Our objective was to determine how CVD risk was addressed by hospitalization (median duration 8.5 days), 2 malignancies and 15 rheumatologists. serious infections (8.8 per 100 patient-years); mostly due to chest Methods: Ethics approval from the University of Calgary Conjoint infection. Of the 12 deaths, 9 were due to progressive ILD with median Health Research Ethics Board was granted to complete a retro- DLCO of 41% (range 35–64%) prior to rituximab. Other deaths were: 1 spective chart review on randomly selected patients who were referred lung cancer, 1 colon cancer and 1 infection post-surgery. Median time to our Early Inflammatory Arthritis (EIA) Clinic between January 2009 from last rituximab infusion to death was 11.5 months (range 6–72). and December 2012. Demographic data was recorded on all patients Conclusion: Mortality rates and SAEs, although notable, are as might at baseline. The following variables were collected at baseline, 6 be expected for this advanced RA cohort with multiple comorbidities. month and 12 month visits: DAS for 28 joints (DAS28)-ESR, all Most patients with stable ILD before rituximab remained stable over medications, traditional CVD risk factors, and diagnoses of CVD. We prolonged follow up. Due to the time elapsed since last rituximab, and calculated Framingham Risk Scores (FRS) based on lipids and BMI since the patients who died or deteriorated had the most severe ILD and QRISK2 scores. We also extracted the rheumatologists’ recom- before rituximab, these observations suggest the drug may not be mendations for CVD risk reduction. necessarily causative. Analysis of detailed respiratory investigations is Results: We included 150 patients (70% female, 89% Caucasian, in progress and will help to identify patients whose ILD improved after mean age 52 years), who met ACR/EULAR 2010 criteria for RA. The treatment. mean baseline DAS28 score was 5.17 (S.D. 1.31). At 12 months, 63% of Disclosure statement: Md.Y.Md.Y. has received funding from the patients achieved low disease activity or remission. 89 (60%) patients NIHR. S.D. has received honoraria from Roche and GSK. E.M.V. has had at least one CVD risk factor (exclusive of RA); 16 (18%) had two, received honoraria and research grants from Roche and GSK; and has 15 (17%) had three, and 9 (10%) had more than three risk factors. received funding from the NIHR. P.E. has received consultant fees Obesity 27 (30%), smoking 25 (28%) and hypertension 20 (23%) were from BMS Abbott, Pfizer, MSD, Novartis, Roche and UCB; and has the most common risk factors. Documentation of the discussion received research grants from Abbott, BMS, Pfizer, MSD and Roche. around CVD risk was only found for 1 patient. The FRS risk score could All other authors have declared no conflicts of interest. only be calculated in 123 patients with 13% at high risk using the FRS Lipid calculation and 17% at high risk using the FRS BMI calculation. QRISK2 could be calculated for 52 patients of which 23% had high risk 093. HOW EFFECTIVE IS RITUXIMAB IN THE TREATMENT scores of ^20%. Once the EULAR recommended 1.5 times multi- OF RHEUMATOID ARTHRITIS IN THE PRESENCE OF plication factor for RA was applied, the high-risk category for both FRS CHRONIC LUNG DISEASE? calculators nearly doubled. Of 38 patients with existing CVD risk, 35 Kundan Iqbal1, Vadivelu Saravanan1, Jennifer Hamilton1, had this risk managed by another physician. Three cardiac events Carol Heycock1, Martin Rynne1 and Clive Kelly1 were observed during the first year of disease. 1Queen Elizabeth Hospital, Rheumatology, Gateshead, UK Conclusion: Although these early RA patients are achieving disease targets, their CVD risks are not being addressed. Nearly half of this Background: RA is an autoimmune disease characterized by articular cohort had intermediate to high FRS and QRISK2 risk scores before inflammation. However, 40% of RA patients demonstrate extra- applying the recommended RA multiplication factor. We now articular manifestations, prominent among which are pulmonary recognize the need to address this issue and will do so through a complications, particularly bronchiectasis and interstitial lung disease multidisciplinary and multi-target care model. (ILD). Lung disease is directly responsible for 25% of all RA mortality, Disclosure statement: The authors have declared no conflicts of but an evidence base for the treatment of severe RA in the presence of interest. lung disease is still at the formative stage. Anti-B cell CD20 antibody rituximab may be a promising therapeutic option. 092. EFFICACY AND SAFETY OF RITUXIMAB IN Methods: We aimed to assess the efficacy of rituximab therapy in RHEUMATOID ARTHRITIS PATIENTS WITH CONCOMITANT patients with RA and either bronchiectasis or ILD, and to compare this INTERSTITIAL LUNG DISEASE: 10-YEAR EXPERIENCE AT to RA controls matched for age, gender and disease duration. We SINGLE CENTRE undertook a retrospective review of 53 RA patients from one UK centre receiving rituximab. The presence of pulmonary comorbidity was Angela R. Kabia1, Md Yuzaiful Md Yusof1,2, Shouvik Dass1,2, Edward 1,2 3 1,2 noted. In all patients articular DAS pre- and post-rituximab were M. Vital , Paul Beirne and Paul Emery recorded. In those with lung disease, baseline and follow-up lung 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, 2 function data (vital capacity and gas transfer) were also recorded. The University of Leeds, NIHR Leeds Musculoskeletal Biomedical study was registered with Gateshead Trust with ethical approval. Research Unit, Leeds Teaching Hospitals NHS Trust and 3 Students t-test was used for all statistical comparisons. Department of Respiratory Medicine, Leeds Teaching Hospitals Results: Mean age of the rituximab treated RA population was 66 NHS Trust, Leeds, UK years, and 40 were female. Mean baseline DAS28 scores were lower in patients with lung disease (5.0) than in those without (5.4) (P ¼ 0.03), Background: Interstitial lung disease (ILD) is a common extra-articular but mean reductions in DAS28 post-rituximab over 3 years were manifestation in RA and is associated with increased mortality. greater in those with lung disease (–1.9) than in those without (–1.4) Worsening of ILD has been reported in patients receiving TNF (P ¼ 0.01). In those with lung disease, there were non-significant falls in inhibitors, therefore rituximab is commonly used instead. However percent predicted values of vital capacity (–4%) and gas transfer (–3%) evidence of efficacy and safety of rituximab in RA-ILD from cohort over the same period. studies/registries is scarce as these patients are often excluded from Conclusion: Rituximab leads to significant improvements in DAS28 clinical trials. Our aims were to evaluate whether rituximab therapy led scores in RA patients with and without lung disease. Indeed, the to worsening of lung function in patients with previously stable ILD and benefit appeared greater among those with lung disease, in spite of to evaluate serious adverse events (SAEs) and serious infection. lower baseline scores. No significant changes in pulmonary function Methods: We conducted an observational study of consecutive RA were seen as a result of treatment. Therefore, for RA patients with patients with ILD (detected by high-resolution CT prior to rituximab) in chronic lung disease requiring biologic therapy, our data suggest a single centre between January 2004 and July 2014. Each cycle rituximab is both effective and well tolerated, with no evidence in this consisted of 2 1000 mg infusions, repeated on clinical relapse. study to suggest that rituximab influences pulmonary function. Pulmonary function test parameters [forced vital capacity (FVC) and Disclosure statement: The authors have declared no conflicts of carbon monoxide diffusing capacity (DLCO)] were recorded at base- interest. line, 6–12 months post-rituximab and latest time point. SAEs were POSTER VIEWING I Tuesday 28 April 2015 i87

094. TRIAL OF ATORVASTATIN FOR THE PRIMARY the only way of assessing for liver fibrosis is through liver biopsy. This PREVENTION OF CARDIOVASCULAR EVENTS IN PATIENTS is the first study investigating the incidence of liver fibrosis in RA WITH RA (TRACE RA): A RANDOMIZED TRIAL IN 2986 RA patients on MTX with normal LFTs using FibroScan PATIENTS Methods: This is a pilot, prospective, cross-sectional cohort study. 1,2 3 4 Patients attending Rheumatology outpatient clinics who fulfil the George D. Kitas , Peter Nightingale , Jane Armitage , criteria are invited to participate. Names are forwarded to the Naveed Sattar5, Jill J. F. Belch6 and Deborah P. M. Symmons7 1 hepatology team who perform the FibroScan. Inclusion criteria were Rheumatology, Dudley Group NHS Foundation Trust, West diagnosis of RA (sero-positive and negative) on MTX for 2 years and Midlands, 2Arthritis Research UK Centre for Epidemiology, University 3 no abnormal LFTs since starting MTX. Exclusion criteria were other of Manchester, Manchester, Wolfston Computer Laboratory, types of arthritides and patients unsuitable for FibroScan. We aim to University Hospitals Birmingham NHS Foundation Trust, 4 recruit enough patients to obtain 100 FibroScan results, and have Birmingham, Clinical Trials and Epidemiology, University of Oxford, extended the study to achieve this. A FibroScan result of 8KPa is 5 Oxford, Metabolic Medicine, University of Glasgow, Glasgow, considered abnormal. Chi-squared tests and t-tests were used to 6 7 Vascular Medicine, University of Dundee, Dundee and Arthritis compare results and demographic characteristics. Correlations Research UK Centre for Epidemiology, University of Manchester, between dose and duration of MTX treatment were calculated using Manchester, UK linear regression tests. Results: At the time of this interim report, 51 patients were Background: Patients with RA are at increased risk from cardiovas- approached. 39 patients had FibroScans, 6 did not attend their cular disease (CVD) compared with the general population, due to FibroScan appointments, 2 are awaiting their appointment and 4 classical (e.g. hypertension and dyslipidaemia) and novel (e.g. declined. 2 failed the study: no reading was obtainable from 1 patient systemic inflammation) risk factors. It remains unclear whether primary despite using different probes; and only 3 readings were obtainable prevention strategies for CVD are effective in conditions of high grade from the other due to obesity and poor mobility, so the result deemed inflammation such as RA. The TRial of Atorvastatin for the primary invalid. Statistical analysis was performed on the 37 valid FibroScan prevention of Cardiovascular Events in patients with Rheumatoid results. The mean age was 66.6 years (S.D. 7.9), and there were 22 Arthritis (TRACE RA) addressed the hypothesis that atorvastatin 40 mg females (59.5%) and 15 males (40.5%). 3 patients had abnormal daily is superior to placebo for the primary prevention of CVD events in FibroScan results (AFR): 9.1, 8.6 and 8.1. Liver biopsies showed non- RA (ISRCTN: 41829447). alcoholic steatohepatitis in 2 patients. After assessment, the third is Methods: Prospective, randomized, double-blind, placebo-controlled, awaiting a repeat FibroScan in a year. The first two patients stopped multicentre trial in RA patients aged >50 years or RA duration >10 MTX and the third continued. There are no patients with liver fibrosis. years; without known atherosclerotic disease, diabetes, myopathy; not The incidence of AFR is 8%. With 1073 patient-years, the rate of AFR already taking statin. All patients were given lifestyle advice. The is 2.8/1000 patient-years. The correlation coefficient, R ¼ 0.047 primary endpoint was a composite of CVD death, non-fatal myocardial (P ¼ 0.79), indicating no correlation between duration of MTX treatment infarction, cerebrovascular accident (excluding haemorrhagic stroke), and AFR. There was no association between MTX dose and AFR transient ischaemic attack, hospitalized angina, coronary and non- (R ¼ –0.24, P ¼ 0.16). coronary revascularization. Secondary endpoints included safety Discussion: This interim report with small subject numbers shows liver outcomes and lipid changes. The trial was designed to have 80% fibrosis is very rare in RA patients taking MTX with normal LFTs. power at P < 0.05 to detect a 32% risk reduction with atorvastatin Additional routine monitoring with FibroScan is not indicated. This is based on 1.8% event rate, using intention to treat analysis over 5 reassuring as currently LFTs are our routine means of monitoring for years. Cox regression stratified by centre, Fisher’s exact test and the MTX liver side effects. There is no correlation between dose and Mann–Whitney test were used for analysis, as appropriate. duration of taking MTX with AFR. We hope to provide a complete Results: Trial duration was August 2007 to December 2012. A total of report with larger number of patients in due course. 2986 patients from 102 centres were randomized and followed up for a Conclusion: MTX-related subclinical liver fibrosis in RA patients with median of 2.53 years (interquartile range 1.94–3.50), providing 7908 normal LFTs is rare. patient-years of follow up. Atorvastatin and placebo groups were well- Disclosure statement: The authors have declared no conflicts of matched for age, sex, ethnicity, weight, BMI, RA duration, activity, interest. severity and seropositivity, blood pressure, lipid and glucose levels, diabetes, family history of CVD or diabetes. Current smoking was higher in the atorvastatin group (18.4% v 14.5%, P ¼ 0.019). Reduction 096. THE IMPACT OF ANTI-TUMOUR NECROSIS FACTOR in low-density lipoprotein cholesterol (LDL-c) levels was significantly ALPHA THERAPY ON PLATELET FUNCTION, LIPID PROFILE, higher in the atorvastatin group (1.07 mmol/l) compared with placebo AND INSULIN METABOLISM IN PATIENTS WITH (0.14 mmol/l, P < 0.001). In the atorvastatin group 24 patients had a INFLAMMATORY ARTHRITIS: A PROSPECTIVE COHORT CVD event, compared with 36 in the placebo (hazard ratio 0.66, 95% STUDY CI 0.40, 1.11, P ¼ 0.119). The overall event rate was lower (0.76%) than Paul A. MacMullan1, Ann M. Madigan2, Paola Bagaglia2, Laura anticipated (1.80%) and the investigators were instructed by the J. Durcan2, Dermot Kenny3 and Geraldine M. McCarthy2 funders to terminate the trial early. Any reported adverse events were 1Rheumatology, University of Calgary, Calgary, AB, Canada, similar: 294 (19.7%) in the atorvastatin and 292 (19.5%) in the placebo 2Rheumatology, Mater Misericordiae University Hospital, Dublin and group, P ¼ 0.927. 3 Conclusion: Atorvastatin 40 mg daily resulted in significantly greater MCT, RCSI, Dublin, Ireland reduction of LDL-c compared with placebo. The 34% (60% to þ11%) reduction of risk for a major CVD event compared with placebo, Background: Patients with inflammatory arthritis die prematurely from although not statistically significant due to the early termination of the cardiovascular disease (CVD). This increased CVD risk is not fully trial, is in line with expectations based on the Cholesterol Treatment explained by traditional risk factors, is strongly associated with Trialists’ Collaboration meta-analysis of the effect of statins in other inflammation and is significantly reduced in those who respond to populations. Statin therapy was safe in patients with RA. anti- TNF therapy. Platelets play a crucial role in the pathogenesis of Funding: This work was funded by an unrestricted educational bursary atherothrombotic events. Paradoxical lipid profiles and increased rates from Arthritis Research UK, the British Heart Foundation and Pfizer. of insulin resistance have also been shown to strongly correlate with Disclosure statement: Authors have declared no conflict of interest. CVD risk in patients with inflammatory arthritis. We have previously shown enhanced platelet reactivity in patients with active inflammatory arthritis compared with those in remission. Therefore, we decided to 095. THE INCIDENCE OF SUBCLINICAL LIVER FIBROSIS IN prospectively assess the influence of improved disease control with RHEUMATOID ARTHRITIS PATIENTS ON LONG-TERM anti-TNF therapy on platelet function, lipid profiles and insulin METHOTREXATE WITH NORMAL LIVER ENZYMES metabolism in patients with inflammatory arthritis. Methods: Patients with an established diagnosis of inflammatory Malack Alachkar1, Thiriloganathan Mathialahan2, Sandra Walsh2 and arthritis (RA, PsA, seronegative SpA) and who were due to commence Vun Lim1 anti-TNF therapy were recruited. Patients with a history of CVD, 1Rheumatology and 2Gastroenterology, Wrexham Maelor Hospital, diabetes mellitus or receiving anti-platelet therapy or cholesterol Wrexham, UK lowering medication were excluded. Demographic data, traditional CVD risk factors and medication use were recorded. Patients were Background: FibroScan is a non-invasive assessment of liver fibrosis evaluated on two separate occasions, before commencing an anti- by measuring liver stiffness. Patients with liver fibrosis may not present TNF agent (adalimumab, etanercept, certolizumab, infliximab) and with deranged liver function tests (LFTs). Currently, the only monitoring again after 4 months of treatment. Disease activity assessment for hepatic side effects of MTX is by LFTs, so we cannot confidently comprised serological markers (ESR, CRP, fibrinogen), patient exclude MTX-related fibrosis in patients with normal LFTs. Previously measures (VASDA), evaluator global assessment and the DAS for 28 i88 Tuesday 28 April 2015 POSTER VIEWING I

joints (DAS28) score. Patients were classified as responders by non-significant SMD for ESR (SMD: 0.08, P ¼ 0.25). Disability scores reduction of at least one disease category in DAS28 or >30% were higher in patients with depression, with a difference of 0.84 in improvement in VASDA, where applicable. Samples of fasting lipids, HAQ, threefold greater than the minimum clinically important differ- glucose and insulin were obtained. Insulin resistance was assessed ence of 0.22. using the HOMA-IR method. Lipid atherogenic profile was measured Conclusion: Depression and anxiety have substantial impacts on using the established HDL/LDL ratio. Platelet responses to multiple disease activity measures as well as disability. Their effects on disease concentrations of several agonists (arachidonic acid, collagen, activity are related to higher TJC and PG assessments. It is difficult to epinephrine, TRAP and ADP) were measured simultaneously using a achieve remission if RA patients have substantial psychological modification of light transmission aggregometry and log dose– symptoms. Greater emphasis is needed on managing these problems, response curves were calculated. and research is needed to identify the most effective approaches. Results: Data from 23 patients were analysed (n ¼ 18 responders, Disclosure statement: The authors have declared no conflicts of n ¼ 5 non-responders). Responders had higher DAS at baseline (mean interest. DAS28, 5.6 vs 3.8, P < 0.01) and significantly different atherogenic indices (mean high-density lipoprotein: low-density lipoprotein ratio, 098. EROSIVE AND OSTEOARTHRITIC STRUCTURAL 0.52 vs 0.35) compared with non-responders. Post-treatment platelet PROGRESSION IN EARLY RHEUMATOID ARTHRITIS responses to ADP were significantly reduced in responders only (EC50 1.97 vs 1.17, P < 0.001), while in non-responders, pre/post-treatment Daniel F. McWilliams1, Michelle Marshall2, Keeranur Jayakumar3, values were similar (EC50 1.89 vs 1.94). There were no differences in Sally A. Doherty4, Michael Doherty4, Patrick D. W. Kiely5, pre/post-treatment platelet responses to any of the other agonists for Adam Young6 and David A. Walsh1,7 either group. Responders also demonstrated reduced insulin resis- 1Arthritis UK Pain Centre, Academic Rheumatology, University of tance (mean HOMA-IR 2.68 vs 1.78, P < 0.01) compared with non- Nottingham, Nottingham, 2Arthritis UK Primary Care Centre, responders (2.28 vs 2.31), pre and post-treatment, respectively. Lipid University of Keele, Keele, 3Rheumatology, Heart of England NHS profiles remained unchanged across all subjects. Foundation Trust, Birmingham, 4Academic Rheumatology, University Conclusion: These data are a prospective demonstration of of Nottingham, Nottingham, 5Rheumatology, St George’s Healthcare decreased platelet reactivity and improved insulin sensitivity in NHS Trust, London, 6Rheumatology, West Hertfordshire Hospitals patients with active inflammatory arthritis who respond to anti-TNF NHS Trust, St Albans and 7Rheumatology, Sherwood Forest therapy, and may represent potential mechanisms by which anti-TNF Hospitals NHS Foundation Trust, Sutton-in-Ashfield, UK therapy reduces CVD events in this high-risk population. Disclosure statement: P.A.M. receives unrestricted training grants Background: The aim was to further understand associations and/or investigator initiated funding from AbbVie, Pfizer and Roche. between joint damage, inflammation, pain and disability in early RA, D.K. receives unrestricted training grants and/or investigator and how comorbid OA may influence patient assessment and initiated funding from AbbVie, Pfizer and Roche. G.M.M. receives outcomes. unrestricted training grants and/or investigator initiated funding from Methods: The Early RA Network (ERAN) inception cohort recruited AbbVie, Pfizer and Roche. All other authors have declared no conflicts participants from centres across the UK. Baseline radiographs of of interest. hands/feet were available for 498 participants, and follow-up radio- graphs were assessed for 166 participants after 3 (1) years. Radiographs were scored for RA damage [erosions and joint space 097. PSYCHOLOGICAL COMORBIDITY AND DISEASE narrowing (JSN)] using van der Heijde–Sharp methodology. Hand and ACTIVITY SCORES IN RHEUMATOID ARTHRITIS foot OA were determined according to the presence of osteophytes Faith Matcham1, Aneela Mian2, Sophia Steer2, Nicola Gullick2, David (OST) and scored using validated atlases (OARSI, La Trobe). Clinical L. Scott2, Matthew Hotopf1, Sam Norton3 and James Galloway2 outcomes, DAS for 28 joints (DAS28), its components and DAS28-P 1Department of Psychological Medicine, Institute of Psychiatry, (the proportion of DAS28 attributed to patient-reported factors) were King’s College London, 2Department of Academic Rheumatology, recorded at baseline and follow up. Logistic regression was used to King’s College London and 3Department of Health Psychology, calculate adjusted odds ratios (aOR) and 95% CIs. King’s College London, London, UK Results: At baseline, median (interquartile range RA total radiographic score was 6 (3–12), with 71% displaying erosions. Presence of OA was Background: One-third of people with RA have comorbid depression common (40% hand and 48% foot). Higher baseline RA radiographic or anxiety. Depression worsens disability and is associated with higher scores were associated with increasing age and ESR and lower disease activity states; however, how it corresponds to specific DAS28-P. Baseline summated hand OST scores were associated with disease activity measures is not known. Previous analyses tend to rely older age, more swollen joints, higher ESR, lower DAS28-P, shorter upon non-validated psychological components within other disease symptom duration and seronegative status. Baseline summated foot measures such as those contained in the Short-Form-36. We used OST scores were associated with older age and greater disability. routinely collected data incorporating validated psychological assess- People with higher RA radiographic scores also had higher OA scores. ment tools to explore the relationship between mental health disorders Age was independently associated with each radiographic score after and disease activity. adjusting for other variables. DAS28 and patient-reported outcomes Methods: We compared the DAS for 28 joints (DAS28) assessed in improved, whereas RA and OA radiographic scores deteriorated by patients attending routine RA follow-up clinics with patient-reported 3(1) year follow up. Increases in erosion scores were associated with physical and psychological outcomes captured using an institutional higher baseline erosions score, female gender, better mental health service development tool (IMPARTS). This recorded disability and lower DAS28-P. Greater than median hand OST score progression assessed by the HAQ, depression assessed by nine-item Patient was associated with baseline hand OST score only after adjustments. Health Questionnaire (PHQ) and the seven-item Generalized Anxiety Higher cumulative ESR or VAS-GH values from baseline to year 2 were Disorder scale (GAD). associated with greater RA radiographic progression. Radiographic Results: We studied 341 RA patients: 80% female, 76% seropositive, progression of either RA or OA was not significantly associated with mean age of 57 years and mean disease duration 9 years. 20% had changes in patient-reported outcomes during the first 3 years after RA depression and 21% had generalized anxiety. A total of 54/200 (27%) presentation. active patients (DAS28 over 3.2) were depressed compared with 14/ Conclusion: In individuals with RA, OA frequently co-occurred. During 141 (10%) with low disease activity (DAS28 under 3.2); this difference the first 3 years after RA diagnosis both RA and OA demonstrated was highly significant: odds ratio of being in a low disease state or structural progression, particularly in older ages. Structural progres- remission in depressed patients 0.30 (95% CI 0.16, 0.56). Findings sion may lead to long-term disability, but during early RA has less were similar with anxiety, which affected 28% of active patients and impact on patient-reported outcomes in the short-term than other 11% controls with an odds of low disease 0.31 (95% CI 0.17, 0.57) in factors (e.g. synovitis, sensitization). Therefore comorbid OA could anxious patients. Comparison between patients with and without confound disease assessment in early RA. Individuals with high probable depression for the DAS score components revealed DAS28-P or with worse mental health at baseline underwent less statistically significant moderate to large (as defined by Cohen) erosive progression and should be considered when interpreting standardized mean differences (SMD) for tender joint count (TJC; DAS28 in treatment decisions that aim to reduce RA joint damage. SMD 0.49, P < 0.01) and physician-generated (PG) scores (SMD: 0.84, Holistic approaches to RA treatment are indicated, that address P < 0.01). SMD were small and non-significant for SJC (SMD: 0.15, psychosocial factors and comorbidities, as well as joint inflammation. P ¼ 0.09) and ESR (SMD: 0.11, P ¼ 0.50). A similar comparison Disclosure statement: D.F.M. has received honoraria from Pfizer; and between patients with and without probable anxiety disorder found: has received research funding from Pfizer. D.A.W. has received moderate to large, statistically significant SMD were found for TJC research funding from Pfizer. All other authors have declared no (SMD 0.39, P < 0.01) and PG scores (SMD ¼ 0.73, P < 0.01); a small conflicts of interest. but significant SMD for SJC (SMD ¼ 0.30, P < 0.05); and small and POSTER VIEWING I Tuesday 28 April 2015 i89

099. RISK OF DEVELOPING A FIRST INVASIVE MELANOMA did not show a significantly increased melanoma risk for any of the IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH biologic therapies compared with biologic-naive patients. BIOLOGICS: RESULTS OF A COLLABORATIVE PROJECT OF Conclusion: This large European collaborative project of 11 registers 11 EUROPEAN BIOLOGICS REGISTERS from 9 countries did not confirm an increased risk of melanoma 1 2 2 1 following exposure to TNFi, although an association cannot be Louise Mercer , Johan Askling , Pauline Raaschou , Will Dixon , completely ruled out with these data. Lene Dreyer3, Merete Hetland4, Lene Mellemkjær5, Anja Strangfeld6, 6 7 8 9 Disclosure statement: J.M. has received consulting fees from Roche Angela Zink , Florenzo Iannone , Axel Finckh , Jakub Zavada , Pharmaceuticals, Pfizer, BMS, Union Chimique Belge, Merck Helena Canhao10, Fernando Martins10, Xavier Mariette11, 12 13 14 Pharmaceuticals and Abbott Laboratories. All other authors have Jacques Morel , Jacques-Eric Gottenberg , Adele Green , declared no conflicts of interest. Victoria Herna´ ndez15, Florence Tubach16, Piet van Riel17, Kimme L. Hyrich1 and Joachim Listing6 1Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, UK, 2Clinical Epidemiology Unit, 100. ARE WE SCREENING APPROPRIATELY FOR Karolinska Institutet, Stockholm, Sweden, 3Department of INTERSTITIAL LUNG DISEASE IN RHEUMATOID ARTHRITIS? Rheumatology, Gentofte University Hospital, Hellerup, 4DANBIO, A STUDY INTO THE USE OF LUNG FUNCTION TESTS AT Copenhagen Centre for Arthritis Research, University of PREDICTING ILD Copenhagen, Copenhagen, 5Danish Cancer Society Research Caroline R. Ming1, Andrew P. D. Jeffries1, Matthew Wilkinson2, Centre, Danish Cancer Society, Copenhagen, Denmark, 2 2 2 6 Robert O’Loughlin , David Osborne , Serena Zaman , Epidemiology Unit, German Rheumatism Research Centre, Berlin, 1 1 1 7 8 Patrick Gordon , Nicola Gullick , Sophia Steer and Germany, University of Bari, Bari, Italy, University of Geneva, 1 9 James Galloway Geneva, Switzerland, Institute of Rheumatology, Charles University, 1 2 10 Rheumatology, King’s College Hospital and Medical School, King’s Prague, Czech Republic, Rheumatology Research Unit, College London, London, UK Universidade de Lisboa, Lisbon, Portugal, 11Department of Rheumatology, Universite Paris-Sud, Paris, 12Universite Montpellier, 13 Background: The British Society for Rheumatology (BSR) recom- Montpellier, Department of Rheumatology, CHU, Strasbourg, mends MTX be used with caution in interstitial lung disease (ILD). A 14 France, Institution of Inflammation and Repair, University of baseline chest X-ray (CXR) should be performed prior to commencing 15 Manchester, Manchester, UK, BIOBADASER Registry, Madrid, MTX and if abnormal, pulmonary function tests (PFTs) and high- 16 Spain, De´ partement d’Epide´ miologie et Recherche Clinique, resolution CT (HRCT) scanning considered. Carbon monoxide transfer 17 Universite´ Paris Diderot, Paris, France and Department of factor (TLCO) is reported as the most sensitive indicator of ILD. In our Rheumatic Diseases, Radboud University, Nijmegen, The department, all patients have PFTs before commencing MTX. If TLCO Netherlands is low, HRCT is performed (cut-off <80% non-smokers and <70% smokers). Our objectives were to investigate the relationship between Background: Swedish and Danish national biologics registers have PFTs and abnormalities on CXR and HRCT in MTX naive RA patients, reported a possible increase in melanoma risk with TNF inhibitors. As and review the utility of TLCO in predicting the presence of ILD, as well melanomas are uncommon, the association is difficult to evaluate in as the optimum TLCO threshold. other individual registers. We therefore planned a EULAR collaborative Methods: A departmental database of 800 patients with a diagnosis of project. RA was used to identify patients in whom screening PFTs and HRCT Methods: Patients with RA from 11 European biologics registers in 9 had been performed. Abnormal HRCTs were further classified into ILD countries were included. Patients were followed prospectively from or non-ILD, based upon ILD team reviews. These data were used to start of a new biologic treatment until the occurrence of first invasive calculate the sensitivity-specificity of different cut-off values of TLCO histology-confirmed cutaneous melanoma, using an ever-exposed for predicting HRCT abnormalities. approach. For the TNFi cohort, prior exposure to biologic drugs was Results: 89 subjects were included, 80% female, mean age 59.6 (S.D. not permitted. Prior exposure to TNFi was allowed for other biologic 17). 49% were current or ex- smokers. The most common ethnicities drugs. For each register, incidence rates and standardized incidence were Caucasian (45%) and black African/Caribbean (34%). All patients ratios (SIR) of melanoma were calculated by using age-, sex- and selected for HRCT had abnormal PFTs, and 27% had abnormal CXR. calendar year-specific rates from the general population of the 56 (63%) had an abnormal HRCT. The most common HRCT corresponding country as reference. Poisson regression models abnormality was COPD in 22 patients (39%). ILD was present in 15 were used to summarize the register-specific SIRs to overall SIR (16%): subtypes were usual interstitial pneumonia (7) non-specific estimates. Rates of melanoma in biologic exposed patients were interstitial pneumonia (7) and cryptogenic organizing pneumonia (1). 64 compared with those in biologic-naive patients enrolled in participating had a normal CXR, of whom 34 (53%) had an abnormal HRCT, of registers by calculating incidence rate ratios (IRRs). Overall SIRs and which 9 had ILD. The sensitivity of CXR for detecting ILD was 40%. IRRs were calculated, taking the size of the registers into account. TLCO was <70% in 88% of patients. This cut-off had a sensitivity of Results: Overall, 114 291 patients were available for analysis: mean 82% for detecting ILD, but specificity only 17%. By raising our age 58 years; 74% female. 287 developed a first invasive melanoma. screening threshold in non-smokers to 80%, we performed nine Background population rates varied due to differences in the incidence additional HRCTs, revealing two cases of ILD. Receiver operator by country, calendar years and differences in the age and sex characteristic (ROC) curves were plotted for different values of TLCO distribution of the corresponding RA cohorts (Table 1). The SIRs for and the ROC areas are shown (Table 1). Smoking was a strong biologic naı¨ve patients were similar across the registers whereas there predictor for HRCT abnormality, with 35/43 (81%) having abnormal- was variation in SIRs between TNFi cohorts (Table 1). The overall IRRs ities, 21 (60%) finding COPD and 6 (17%) finding ILD. Non-smokers

099 TABLE 1. Melanomas, standardized incidence ratios and incidence rate ratios in RA treatment cohorts Person-years Population rate, Observed Expected SIR (95% CI) IRR (95% CI) per 100 000 Biologic naive Total 300011 48 160 144.3 1.1 (0.9, 1.4) Referent ARTIS 222496 52 133 115.5 1.2 (1.0, 1.4) Referent (ARTIS) BSRBR 22972 35 9 8.0 1.1 (0.5, 2.1) Referent (BSRBR) DANBIO 27469 57 14 15.7 0.9 (0.5, 1.5) Referent (DANBIO) RABBIT 9916 33 4 3.3 1.2 (0.3, 3.1) Referent (RABBIT) TNF Total 242814 35 106 85.5 1.2 (1.0, 1.6) 1.1 (0.8, 1.6) ARTIS 59166 44 39 26.0 1.5 (1.1, 2.1) 1.3 (0.9, 1.9) BSRBR 90259 31 31 28.1 1.1 (0.8, 1.6) 1.0 (0.5, 2.3) DANBIO 22972 49 18 11.3 1.6 (0.9, 2.5) 1.8 (0.8, 3.9) RABBIT 23103 31 7 7.1 1.0 (0.4, 2.0) 0.8 (0.2, 3.8) GISEA 16180 40 6 6.4 0.9 (0.3, 2.0) SCQM 15605 26 3 4.1 0.7 (0.2, 2.2) ATTRA 8441 22 1 1.8 0.6 (0.0, 3.0) Rheuma.pt 7088 9 1 0.7 1.5 (0.0, 8.3) Rituximab Total 29619 35 13 10.3 1.3 (0.6, 2.5) 1.1 (0.5, 2.9) Tocilizumab Total 5798 33 5 1.9 2.7 (0.8, 8.4) 2.4 (0.6, 10.1) Abatacept Total 4858 29 2 1.4 1.5 (0.1, 30.9) 1.3 (0.2, 7.6) i90 Tuesday 28 April 2015 POSTER VIEWING I

comparatively had fewer abnormal HRCTs 21/45 (47%), of whom 9 0.4, 0.55 and 0.86, respectively, with only modest correlations since they (43%) had ILD. measure different aspects (Spearman’s rho 0.72; kappa 19.3, 25.1, Conclusion: TLCO is a common screening tool for ILD prior to 24.6 and 22.9, respectively). 75% of all comorbidities included only 20 commencing MTX. However, it has important limitations. TLCO was a specific medical conditions. The most common 2–3 specific conditions in poor predictor of HRCT abnormalities in our cohort, with a large each ICD-10 system made up most (70–80%) of each system. For the proportion of HRCTs detecting other lung pathology, predominantly other less common systems, there was a wider range of individual emphysema. Nevertheless, raising the TLCO cut-off to 80% identifies conditions of roughly equal frequencies. Multiple-morbidity cannot be additional cases of ILD. These results illustrate the challenge in measured with CCI but from ICD-10 (>1 major condition) was present in selecting for HRCT prior to commencing MTX, and reinforce the <1%, 11%, 17% and 29% at baseline and at 3, 5 and 10 years. necessity of good clinical evaluation in the process, as investigations Conclusion: Collecting and scoring comorbidity was relatively simple may not provide the full picture. using standard ICD-10 definitions, and identified multiple-morbidity. It Disclosure statement: The authors have declared no conflicts of is this latter group with complex disease that requires prompt interest. identification, multiple speciality input and coordination of patient care in routine clinical settings. Disclosure statement: The authors have declared no conflicts of interest. 100 TABLE 1. Relationship between different TLCO cut-offs and HRCT findings TLCO Patients, n Abnormal ROC area ILD on ROC area cut-off HRCT (95% CI) HRCT (95% CI) 102. COMORBIDITY IN RA. A COMPARISON BETWEEN A (% predicted) SIMPLE COMORBIDITY COUNT AND THE CHARLSON <60 40 28 0.56 (0.46, 0.66) 8 0.53 (0.45, 0.61) MORBIDITY INDEX FOR PREDICTING SURVIVAL AND <65 52 34 0.53 (0.43, 0.63) 11 0.55 (0.48, 0.63) FUNCTION <70 72 46 0.53 (0.39, 0.66) 12 0.50 (0.39, 0.60) 1,2 3 4 5 <75 83 53 0.57 (0.34, 0.79) 14 0.50 (0.33, 0.67) Elena Nikiphorou , Sam Norton , Patrick Kiely , David A. Walsh , Josh Dixey6 and Adam Young1,2 HCRT: high-resolution CT; ROC: receiver operating characteristic; TLCO: carbon 1ERAS & ERAN, St Albans City Hospital, St Albans, 2School of Life & monoxide transfer factor. Medical Sciences, University of Hertfordshire, Hatfield, 3Psychology Department, Institute of Psychiatry, King’s College London, 4Department of Rheumatology, St George’s Healthcare Trust, London, 5Arthritis UK Pain Centre, University of Nottingham, Nottingham and 6Department of 101. COMORBIDITY IN RA. COEXISTENT MEDICAL Rheumatology, New Cross Hospital, Wolverhampton, UK CONDITIONS AND MULTIMORBIDITY CAN BE RECORDED RELATIVELY EASILY IN OBSERVATIONAL RESEARCH Background: Simple counts of coexistent conditions using non- STUDIES. IS IT FEASIBLE TO EXTEND THIS TO ROUTINE standardized systems or the Charlson Comorbidity Index (CCI) are the CLINICAL SETTINGS? most common methods used in RA observational cohort studies to measure comorbidity. This group has reported recently on the 1,2 3 4 5 Elena Nikiphorou , Sam Norton , David A. Walsh , Patrick Kiely , prevalence and incidence of comorbidity in RA using the former. The 6 1,2 Josh Dixey and Adam Young generic and weighted CCI is one of few validated tools, designed for 1 2 ERAS & ERAN, St Albans City Hospital, St Albans, School of Life & acute medical inpatient settings. Disadvantages include its lack of 3 Medical Sciences, University of Hertfordshire, Hatfield, Psychology simplicity and appropriateness in rheumatology outpatients. Currently Department, Institute of Psychiatry, King’s College London, London, unavailable is a standardized, uncomplicated and validated instrument 4Arthritis UK Pain Centre, University of Nottingham, Nottingham, for recording and collecting comorbidity data, which is relevant to 5Department of Rheumatology, St George’s Healthcare Trust, contemporary and routine rheumatology practice, and which compro- London and 6Department of Rheumatology, New Cross Hospital, mises successfully between feasibility in clinical settings and degree of Wolverhampton, UK detail. This study evaluates a simple comorbidity count based on ICD- 10 systems (chapters) to predict survival and functional outcome by 5 Background: Comorbidity in RA can delay diagnosis, influence years in RA. treatment decisions, affect RA outcomes adversely (e.g. survival) and Methods: Two UK inception observational cohort studies of RA confound data analysis. Most RA observational cohorts have used either collected comorbidity and outcome data routinely: the Early RA Study non-standardized but simple counts of coexistent conditions, or the (ERAS; n ¼ 1465) and the Early RA Network (ERAN; n ¼ 1272). weighted Charlson Comorbidity Index (CCI), designed for acute medical Clinicians indicated on yearly case report forms (CRFs) the presence inpatient settings and not appropriate for rheumatology outpatients, but or not of coexistent medical conditions based on the main ICD-10 one of few validated tools. We previously reported the value of a simple systems (cardiovascular, respiratory chapters, etc.), with space to add comorbidity count for assessing prevalence and incidence of comorbid- greater details as free text. The national Medical Research Information ity on survival in RA. There is currently no standardized, uncomplicated Service provided date and cause of death. Cox and multivariate and validated instrument for recording and collecting comorbidity which regression (adjusting for age at disease onset and gender) were used is relevant to contemporary rheumatology practice, and compromises to predict 5 and 10 year survival and functional outcome (HAQ), using successfully between feasibility in clinical settings and degree of detail. both a simple comorbidity count based on the ICD-10 coding system This study evaluates a simple count based on ICD-10 systems (chapters) and the CCI recorded 1 year before. to measure comorbidity in RA. Results: From a total of 2737 patients recruited from 1986 to 2012, Methods: Two UK inception observational cohort studies of RA maximum follow up was 20 and 11 years respectively in the two collected comorbidity data routinely: the Early RA Study (ERAS; cohorts (median 10 and 4 years), median age of onset 55 and 57 years, n ¼ 1465) and Early RA Network (ERAN; n ¼ 1272). Maximum follow up 67% women in both. 1720 (63%) had >4 years follow up. By 5 years was 20 and 11 years respectively, median 10 and 5 years. Clinicians from baseline there were 228 (8%) deaths, mainly from malignancy indicated on yearly case report forms the presence or not of coexistent (29%), cardiovascular (27%), respiratory (21%) and non-cardiac medical conditions based on the main ICD-10 systems (n ¼ 15), with vascular causes (11%). A 5 year HAQ was available for 1442 patients space to add details as free text. (median 0.87, interquartile range 0.25–1.62). Using Cox regression and Results: More than 90% of all comorbidities reported covered 10 multivariate regression techniques, controlling for age and sex, the CCI systems in order of frequency: non-cardiovascular (e.g. hypertension and predicted both 5 and 10 year survival (P ¼ 0.014 and P ¼ 0.03, stroke; to comply with World Health Organization classification), respectively) but not function. The simple comorbidity count predicted cardiovascular, endocrine, gastrointestinal and hepatic, respiratory, 5 year HAQ (P ¼ 0.03), but not 10 year HAQ (P ¼ 0.08) nor survival. psychiatric, malignancies, renal, and skin and eye conditions. Conclusion: This study has shown the value and relative ease of Musculoskeletal and extra-articular RA conditions were excluded from collecting comorbidity data using standard definitions from ICD-10, the main analysis because of their close association with RA and and its ability in predicting function. This simple comorbidity count, likelihood of being managed within the specialty. Graphic displays will together with age onset and sex, was not strongly predictive of survival show the relative frequency of individual comorbidities recorded by the and the CCI remains the most powerful predictor of survival within a two methods. At least one comorbidity was present at baseline and at 3, year of assessment. 5 and 10 year follow up in 21%, 40%, 50% and 78%, respectively, based Disclosure statement: The authors have declared no conflicts of on a simple numerical score, compared with CCI values of 11%, 27%, interest. 36% and 52%. Mean scores were 0.21, 0.53, 0.72 and 1.08 and 0.13, POSTER VIEWING I Tuesday 28 April 2015 i91

103. TUBERCULOSIS AND BIOLOGICS: REAL-WORLD Conclusion: In conclusion, the common predictors of bone loss over EXPERIENCE FROM HIGH TUBERCULOSIS PREVALENCE time in patients with RA are age and first BMD. Steroids interestingly AREA did not predict further bone loss over time. However, the effects of these predictors on the bone loss are small although statistically Muhammad K. Nisar1, Aneesa Rafiq2 and Andrew J. K. Ostor3 1 2 significant. Further research is needed. Rheumatology, Luton & Dunstable University Hospital, Research & Disclosure statement: The authors have declared no conflicts of Development, Luton & Dunstable University Hospital, Luton and interest. 3Rheumatology, Cambridge University Hospitals, Cambridge, UK

104 TABLE 1. The coefficients for the univariate and multivariate analyses looking at Background: Biologic agents have led to a sea change in the the predictors of bone loss management of inflammatory arthritis however higher risk of oppor- tunistic infections particularly tuberculosis (TB) is well recognized. This Predictor Univariate Multivariate Univariate Multivariate has led to the development of TB screening guidelines. The aim of this coefficient coefficient coefficient coefficient (lumbar spine) (lumbar (femoral (femoral study was to investigate the prevalence of latent TB in patients spine) neck) neck) prescribed biologic therapy in a TB endemic area (prevalence 50/100 000) and to assess the risk of subsequent reactivation. Smoker 0.0014 (P ¼ 0.41) –0.0015 (P ¼ 0.23) Age 0.0001 (P < 0.01) 0.002 –0.0001 (P ¼ 0.09) –0.0001 Methods: Retrospective case note review of all patients with First bone –0.0296 (P < 0.01) –0.0291 –0.0230 (P < 0.01) –0.0233 inflammatory arthritis ever prescribed biologic therapy between 1998 density and 2014 at our centre. BMI –0.0001 (P ¼ 0.74) –0.0002 (P ¼ 0.16) Results: 260 patients (95 men, 165 women) who have had biologic Steroid use 0.0001 (P ¼ 0.96) –0.0003 (P ¼ 0.84) therapy over 16 years were included. Mean age upon commencing the Excess alcohol 0.0020 (P ¼ 0.65) –0.0007 (P ¼ 0.84) biologic was 51 years. 177 (68%) participants had RA, 26 (10%) PsA, 42 (16%) axial SpA and 15 (6%) JIA. 190 (73%) patients were Caucasian, 51 (20%) Asian, 12 (5%) Afro-Caribbean and the remaining 7 were mixed race. 209 (80%) prescriptions were issued for TNF 105. INVESTIGATION OF THE PREVALENCE AND inhibitors (91 for etanercept and remaining for mAbs). 31 patients had PHENOTYPE OF ATHEROSCLEROSIS IN PATIENTS WITH rituximab, 17 had tocilizumab and 3 were initiated on abatacept. RHEUMATOID ARTHRITIS Median duration of biologic therapy was 4.2 years for those who Sarah C. Skeoch1, Penny Cristinacce2, Heather Williams3, remained on treatment prior to stopping or switching therapies. Prior Dongxiang Xu4, Sun Jie4, Niranjan Balu4, Jacqueline James3, to the implementation of TB screening in the unit in 2007, 112 patients Chun Yuan4, Thomas Hatsukami4, Paul Hockings5,6, underwent clinical assessment, chest X-ray and check for BCG scar. Yvonne Alexander7, John Waterton2,8 and Ian Bruce1,9 One patient of Asian origin developed extra-pulmonary TB within six 1NIHR Manchester Musculoskeletal Biomedical Research Unit, weeks of adalimumab initiation. Following a year of anti-TB treatment, Centre for Musculoskeletal Research, University of Manchester, he restarted the biologic therapy with no ill effect. 148 participants 2Biomedical Imaging Institute, University of Manchester, underwent additional IFN-g release assay (IGRA) testing as part of new 3Department of Nuclear Medicine, Central Manchester University protocol (T-Spot test). 14 (10%) had positive test with normal chest Hospitals NHS Foundation Trust, Manchester, UK, 4Department of X-rays. Five patients were white, 7 of Asian origin and 2 others. Three Caucasian patients had borderline result. All had 3 months of isoniazid Radiology, University of Washington, Seattle, WA, USA, 5AstraZeneca Drug Safety and Metabolism, AstraZeneca, Sweden, and rifampicin with simultaneous prescription of biologic agent (12 had 6 TNF antagonist, 3 rituximab and 2 tocilizumab). No cases of active TB MedTech West, Chalmers University of Technology, Gottenburg, Sweden, 7Healthcare Science Research Institute, Manchester infection were observed 8 Conclusion: Metropolitan University, Manchester, AstraZeneca Personalised Prevalence of latent TB in patients with inflammatory 9 arthritis prescribed biologic therapy in an endemic area is 10%. The Healthcare & Biomarkers, AstraZeneca, Macclesfield and Kellgren risk is independent of ethnicity and warrants careful screen and Centre for Rheumatology, Central Manchester University Hospitals monitoring in all patients. Adherence to strict screening protocol NHS Foundation Trust, Manchester, UK reduces the risk of active TB infection irrespective of the biologic therapy employed. Background: Chronic inflammation may contribute to accelerated Disclosure statement: M.K.N. has received honoraria from Roche, atherosclerosis and cardiovascular disease in RA. Emerging evidence AbbVie and UCB; and has received research grants from AbbVie and suggests that RA patients may have a more inflammatory high-risk Roche. A.J.K.O. has received honoraria from Roche, Chugai, atherosclerotic plaque phenotype. Non-invasive imaging techniques Schering-Plough/MSD, Abbott, Wyeth, BMS, GSK, MerckSorono including MRI and PET can be used to evaluate carotid plaque burden, and UCB. The other author has declared no conflicts of interest. composition and inflammation. The aim of the current study was to test the hypothesis that RA patients have a more inflammatory complex plaque phenotype compared with controls. 104. PREDICTORS OF BONE LOSS OVER TIME IN PATIENTS Methods: A prospective case–control pilot study of patients with WITH RHEUMATOID ARTHRITIS: AN OBSERVATIONAL STUDY active established RA and age and sex-matched controls was conducted. Subjects with a history of statin use, renal impairment or Richa Sinha1 and Marwan Bukhari1 contra-indication to MRI were excluded. Subjects underwent clinical 1Rheumatology, Royal Lancaster Infirmary, Lancaster, UK and serological evaluation, then carotid artery ultrasound was performed to screen for plaque. Dynamic contrast enhanced carotid Background: RA is a well-known cause of bone loss. The only study MRI was performed in those with plaque >2.5 mm thick to evaluate to date showed that, bone loss in patients with RA was early in the plaque volume, composition and inflammation. A subgroup of patients disease and was associated with disease activity. The aim of this had a carotid PET scan to measure plaque inflammation. Non- longitudinal study was to determine the associations of bone loss over parametric statistics were used to evaluate differences between time in patients with RA. patients and controls and associations between imaging, clinical and Methods: Data from male and female patients who had RA attending serological parameters. for more than one DXA assessment between 2004 and 2014 in the Results: 130 patients and 52 controls were recruited to the study. North West of England was used. The rate of bone loss over time was Median [interquartile range (IQR)] age of patients and controls was calculated in change in BMD per year. This was then used as an 55.5 (48.8–61.9) and 56.4 (48.0–60.4) years respectively (P ¼ 0.97). 99 outcome variable for a univariate and a step wise multivariate linear (76.2%) patients and 41 (78.8%) controls were female regression including age, BMI, first BMD, steroid therapy, smoking and (P ¼ 0.761).Median (IQR) disease duration was 11 (6–25) years and excess alcohol history. This was modelled for the spine (L1–L4) and DAS for 28 joints (DAS28) score was 4.52 (4.32–5.13).There was a the hip. significantly higher prevalence of carotid plaque in patients compared Results: 591 patients were included in the study. The mean age of with controls (53% vs 37%, P ¼ 0.04). Presence of plaque in patients patients was 60.86 (interquartile range: 53.23–69.79). 82% of the was significantly associated with smoking, DAS28, IL-6 and CRP patients were female. The mean bone loss rate in the spine was levels (P ¼ 0.02, P < 0.001, P < 0.001, P ¼ 0.04, respectively). MRI data 0.0005 g/cm2/year. In the univariate and multivariate analysis looking were available in 15 patients and 5 controls. On MRI there was a higher at bone loss rate in the lumbar spine, first BMD and age were found to prevalence of calcified carotid plaques in patients compared with be statistically significant predictors of bone loss in this cohort. controls (73.3% vs 20%, P ¼ 0.038) despite there being no difference Similarly, in the femoral neck, age and first BMD were the only in size of lesions between the groups. No significant difference in significant predictors of bone loss. Table 1 shows the coefficients for plaque inflammation was detected between the groups on MRI. both the univariate and multivariate analyses done on lumbar spine However on PET imaging plaque inflammation was seen in all 13 (L1–L4) and femoral neck (left). subjects scanned. Plaque inflammation on PET was significantly i92 Tuesday 28 April 2015 POSTER VIEWING I

associated with CRP levels(r ¼ 0.58, P ¼ 0.04) and also with expansion Results: The survey was conducted between January and March of CD4(þ) CD28(null) T cells known to be associated with high-risk 2014. The study cohort consisted of 878 patients (Table 1). 98% of plaque in the general population (P ¼ 0.045). vaccination was undertaken by primary care providers. Vaccination Conclusion: This study confirms a higher prevalence of atherosclero- rates were similar across all sites. Influenza vaccine was administered sis in RA and provides preliminary evidence to suggest a more in 83% of patients while only 47% received pneumococcal vaccina- complex plaque phenotype. Although no difference in plaque tion. 13 patients reported they had actively declined vaccination. 6% inflammation was observed on MRI, measurement may have been of respondents reported that they had been informed the vaccination confounded by the high prevalence of calcification in the RA group. was not recommended. Increasing age and comorbidity were On PET imaging all patients had evidence of plaque associated with increased vaccination uptake. In patients under the inflammation which could represent simultaneous joint and plaque age of 65, only 71% received influenza vaccination while 31% received inflammation. Longitudinal studies are needed to further investigate pneumococcal vaccination. Patient-reported infection rates were high this relationship. (41% reported requiring oral antibiotics in the preceding year). The Disclosure statement: S.C.S. has received a research grant from the incidence of hospitalized infection per 100 patient-years follow up was AstraZeneca University of Manchester Strategic Alliance Fund. D.X. 0.05 (95% CI 0.041, 0.06). Respiratory infections represented 74% of has received consultancy fees from VP diagnostics. C.Y. has received reported admissions due to infection. Numbers were too small to grants from the NIH, Philips Healthcare and VPDiagnostics; and serves afford reliable estimates of admission rates in vaccinated and as a consultant for ImagePace and Boehringer-Ingelheim. T.H. has unvaccinated subjects. A striking observation was an almost doubling received funding from Phillips Healthcare. P.H. is an employee of in infection rates in patients on steroids (9% vs 4%). AstraZeneca. J.W. J.W is an employee of AstraZeneca. I.B. has Conclusion: Pneumococcal vaccine uptake compared with influenza received honoraria from GSK, Roche and Pfizer; has received vaccination is poor; possibly due to a lack of patient choice, education speakers fees from the GSK, Pfizer, Medimmune, Merck Serono and or a deficiency in the healthcare provider’s knowledge. The infection UCB; and has received research funding from GSK, Roche and UCB. data on oral antibiotic use highlights the significant burden of infection All other authors have declared no conflicts of interest. in RA with hospitalized episodes representing the tip of the iceberg. A limitation of this large cross-sectional vaccination survey includes potential recall bias and misclassification. Collaborative and proactive 106. MITIGATING INFECTION RISK. INFLUENZA AND approaches to vaccination between primary and secondary care (e.g. PNEUMOCOCCAL VACCINATION IN PATIENTS WITH vaccination education campaigns) are required to increase awareness RHEUMATOID ARTHRITIS: A MULTICENTRE CROSS- and vaccination rates. SECTIONAL SURVEY Disclosure statement: The authors have declared no conflicts of Sujith Subesinghe1, Andrew P. D. Jeffries1,2, Megan Whittaker3, interest. Laura Attipoe1, Fowzia Ibrahim3, Michael Austin1, Zoe Rutter- Locher1, Inam Haq4,5, Helen Harris6 and James Galloway1,3 1 107. POSITIVE IMPACT OF DOLGELLAU COMMUNITY Department of Clinical and Academic Rheumatology, King’s College HOSPITAL HEALTHY HEARTS PROGRAMME ON Hospital, London, 2Department of Rheumatology, Brighton and 3 CARDIOVASCULAR RISK IN PATIENTS WITH RHEUMATOID Sussex University Hospitals, Brighton, Department of Academic ARTHRITIS: 1-YEAR RESULTS Rheumatology, King’s College London, London, 4Rheumatology, Brighton and Sussex University Hospitals, Brighton, 5Division of Anne Thomas1, Sarang Chitale1,2 and Sharon Jones1 , Brighton and Sussex Medical School, Brighton 1Outpatient Department, Dolgellau Hospital, Gwynedd and 2PMRC, and 6Department of Rheumatology, NHS Fife, Kirkcaldy, UK LLandudno Hospital, Conwy, UK

Background: Infections are more frequent in RA, the respiratory tract Background: The award winning Dolgellau Community Hospital (DCH) being a common site. The multifactorial aetiology reflects an Healthy Hearts Programme (HHP) was developed in 2011 and interaction between immunological dysfunction, disease activity and extended to RA patients in September 2012. We presented the immunosuppression. Vaccination is a method of mitigating this risk. baseline data on 20 RA patients as regards to their lifestyle Annual vaccinations against influenza and a one-off pneumococcal cardiovascular disease (CVD) risk factors, CVD risk as measured by vaccination are recommended for people over 65, those with Q-Risk 2 and patient chosen interventions to adopt a healthy lifestyle comorbidity and immunocompromised individuals. Evidence exists last year. The aim of the current study was to assess changes to that vaccine use is highly variable (30–70%) based on small historic lifestyle risk factors and CVD risk in these 20 RA patients at 1 year from audits. We undertook a survey of vaccine uptake across multiple UK their baseline HHP assessment. hospitals (teaching and non-teaching environments). Our primary aim Methods: All established RA patients had an annual 30-min HHP was to identify the proportion of people being vaccinated against lifestyle assessment, including diet, smoking status, activity levels and influenza and Pneumococcus. Secondarily, we identified factors salt consumption at baseline. Comorbidities, blood pressure, BMI, associated with vaccination uptake and explored the relationship cholesterol and blood glucose were recorded. CVD risk over 10 years between vaccination and infection. was calculated using Qrisk2 and a relative CVD risk [adjusted relative Methods: A patient questionnaire was used to collect data. Patients risk (adjRR)] was generated. All patients were offered health promotion were asked about their vaccination history, reasons for non-vaccina- advice and literature. Patients with a high adjRR (>3) were offered 6 tion and also self-reported history of infections. For a subset of HHP sessions for support to achieve patient set goals of weight loss, patients, primary care physicians provided validation data on smoking cessation, healthy diet and increased activity etc. All lifestyle vaccination status. At a single centre, access to hospital episode data was re-captured and Qrisk2 recalculated at 1 year. statistics data was possible and admission rates secondary to Results: 20 RA patients (17 female, 3 male) with a mean age of 65 infection were estimated. All identified admissions were validated by years (S.D. 11 years) and were reassessed at 1 year. Table 1 describes case note review. the baseline and 1-year data on lifestyle CVD risk factors. There was

106 TABLE 1. Detailed demographics of study cohort, including single-centre cohort detailed analysis Influenza vaccination Pneumococcal vaccination

Total cohort (n ¼ 878 Yes No P-value Yes No P-value Vaccinated, n (%) 733 (83) 145 (17) 417 (47) 461 (53) Oral antibiotic use within 12 months, n (%) 308 (42) 48 (33) 182 (44) 174 (38) Admission due to severe infection within 12 months, n (%) 60 (8) 8 (6) 29 (7) 39 (8) Subset from single centre (n ¼ 410) Yes No Yes No Vaccinated, n (%) 323 (78.8) 87 (21.2) 168 (41) 242 (59) Age, mean (S.D.), years 66.45 (13.6) 56.34 (14.2) <0.001 68.7 (13.4) 61.2 (14.2) <0.001 Female, n (%) 251 (77) 72 (82) 0.307 139 (82.7) 184 (76) 0.102 Lung comorbidity, n (%) 43 (13.3) 6 (6.9) 0.102 28 (16.7) 21 (8.7) 0.014 Cardiovascular comorbidity, n (%) 43 (13.3) 6 (6.9) 0.102 13 (6.7) 6 (2.5) 0.013 Diabetes mellitus, n (%) 36 (11.2) 2 (2.3) 0.012 23 (13.7) 15 (6.2) 0.013 Taking MTX, n (%) 208 (64.4) 46 (52.9) 0.049 113 (67.2) 141 (58.2) 0.065 Taking biologic DMARD, n (%) 89 (27.6) 25 (27.6) 0.995 61 (36.3) 52 (21.5) 0.001 Taking oral steroid, n (%) 53 (16.4) 15 (17.2) 0.853 37 (22) 31 (12.8) 0.014 POSTER VIEWING I Tuesday 28 April 2015 i93

some reduction in most lifestyle risk factors with highest reduction in obtained prior to starting a DMARD treatment (intended to correspond salt intake at 1 year. Overall there was a statistically significant to their baseline characteristics if they had been recruited to a trial). reduction in the number of patients with Qrisk 2 >20 at 1-year Results: These results are displayed in a tabulated form below (Table (P ¼ 0.02), as most patients had four or more lifestyle CVD risk factors 1). There was a statistically significant difference in disease duration at baseline. between MIPA; 4.9 years (7.5) and the hospital cohort 8.3 years Conclusion: This study demonstrates that a small improvement in (8.0) (P 0.001). Patients recruited to the RESPOND study had a each individual lifestyle CVD risk factors has a cumulative effect on similar disease duration to MIPA, 3.25 (2.65) vs 4.9 years (7.5) but significantly reducing the overall CVD risk in these RA patients. those in the Toronto observational cohort had the longest disease Community Hospitals and Primary Care facilities are well suited to duration 12 years (9.25). There was a statistically significant undertake and promote interventions such as the HHP which are likely difference between the mean tender and swollen joint counts (TJC to make a significant impact on CVD risk reduction in the general and SJC) between the hospital cohort and MIPA, with patients population at a very low cost. recruited to MIPA having more tender [12.8 (11.2) vs 6.9 (7.3), Disclosure statement: The authors have declared no conflicts of P 0.001] and swollen joints [8.3 (7.9) vs 3.5 (3.7, P 0.001]. In interest. comparison, those recruited to the TORONTO observational study had similar TJC and SJC to the hospital cohort [6.6 (6.9) and 4.3 (4.2)]. Those recruited to the RESPOND study had a much higher TJC and 107 TABLE 1. CVD risk factors and QRISK2 at baseline and 1 year following the HHP in 20 RA patients SJC than MIPA [20.6 (12.3) and 14.7 (9.8)]. Conclusion: The results of this study suggest that patients recruited to CVD risk factors Patients Patients RR (95%Cl) trials of both non-biologic and biologic DMARDs are generally not at baseline at 1-year assessment, assessment, representative of those seen in the selected cohort of patients seen in n (%) n (%) routine care, especially with regard to TJC and SJC, thus the inferences from these studies may not be generalizable. Patients Hypertension (systolic 10 (50) 7 (35) 0.73 (0.37, 1.42) BP >130 with or without recruited to MIPA had generally shorter disease duration, compared medication) with routine hospital cohort. The disease duration in MIPA was similar BMI>25 12 (60) 10 (50) 0.82 (0.44, 1.52) to that of patients recruited to the RESPOND study, however, Low activity levels (<30 min of 8 (40) 6 (30) 0.78 (0.39, 1.6) RESPOND study patients were generally more active with respect to exercise per week) TJC and SJC, which might explain the positive ACR response in both Current smoker 6 (30) 5 (25) 0.88 (0.42, 1.8) arms of the study, despite the same dose of MTX as used in MIPA High salt intake (consumption 14 (70) 1 (5) 0.09 (0.01, 0.59) Disclosure statement: The authors have declared no conflicts of in cooking, table and processed foods) interest. Poor diet (<3 fruit/vegetables 10 (50) 10 (50) No change per day) Qrisk2 >20 11 (55) 4 (20) 0.42 (0.18, 1.01) 109. AN ESSENTIAL PART OF THE RHEUMATOLOGIST’S High adjusted RR >3 5 (25) 3 (15) 0.8 (0.27, 1.27) TOOLKIT? AN AUDIT OF A RHEUMATOLOGY LED ULTRASOUND GUIDED SYNOVIAL BIOPSY SERVICE BP: blood pressure; CVD: cardiovascular disease; RR: relative risk. Arti Mahto1, Ilias Lazarou1, Nora Ng1, Maria DiCicco1, Gina Tan1, Frances Humby1, Costantino Pitzalis1 and Stephen Kelly1 1Department of Experimental Medicine and Rheumatology, Queen Mary University, London, UK

MISCELLANEOUS RHEUMATIC Background: Synovial biopsy is an invaluable investigation for DISEASES rheumatologists and can be utilized to guide diagnosis, treatment and novel research. Traditionally, this has been an invasive arthro- scopic procedure performed by orthopaedic surgeons. For the last 3 years within our Rheumatology Department we have been using a 108. REVIEW OF THE INCLUSION CRITERIA OF CLINICAL minimally invasive US-guided synovial biopsy technique for diagnostic TRIALS IN PSA WITH A COMPARISON WITH ROUTINE CARE tissue analysis. This audit was undertaken to assess current activity, COHORT tissue quality, safety and pathological outcomes. Methods: This was a retrospective audit conducted of patients Anthony O. Agbobu1 and James Galloway1 referred for an outpatient ultrasound guided synovial biopsy from May 1Rheumatology, King’s College Hospital, London, UK 2011 to October 2014. Data was collected from the online care record system and individual patient notes. All patients underwent biopsies Background: In PsA, the first-line agent for many clinicians remains performed by a trained operator under sterile conditions in a dedicated MTX, despite an RCT (MIPA) showing no evidence of superiority over procedure room. Following an initial ultrasound assessment of synovial placebo. This has led to questions over why MIPA failed given that thickening and power Doppler signal, a 14 or 16 gauge core biopsy many clinicians anecdotally report success in use, as well as inferred needle is introduced under ultrasound guidance into the appropriate data of response rates with MTX noted in comparator arms in clinical joint. The tissue is then collected and stored in formalin for trials of anti-TNF. We hypothesized that an important reason under- histopathological analysis and sent fresh to microbiology for tissue pinning the differences in response rates in different trials is the culture and crystal analysis. baseline disease severity, acknowledging that PsA is a more Results: 80 referrals were made to the service. Of these, 74 heterogeneous disease than other inflammatory arthritides. procedures were completed. Demographics: 43 males and 31 females Methods: PubMed search for RCTs including MTX as either an underwent biopsy, age range 17–96. Median time to procedure was 7 intervention or as part of a comparator arm in PsA were identified days. Joints biopsied: knees (31%, n ¼ 23), wrists (31%, n ¼ 23), small through using predefined search criteria. Baseline data from the joints (15%, n ¼ 11), tendon sheath (8%, n ¼ 6) ankles (8%, n ¼ 6), studies were collated and compared using parametric and non- elbows (5%, n ¼ 4) and shoulder (1%, n ¼ 1). Indications: 68% (n ¼ 50) parametric statistical tests as appropriate. Comparisons were then were referred for exclusion of septic arthritis, 50% made specific made between these characteristics and the characteristics of a reference to mycobacterium tuberculosis (TB) infection. 19% (n ¼ 14) cohort of routine care patients with PsA attending a single teaching were referred to investigate potential crystal arthropathies and 11% hospital in London. Baseline characteristics, for analysis, were (n ¼ 8) for sarcoidosis. Outcomes: 10% (n ¼ 5) of patients referred for

108 TABLE 1. Baseline disease characteristics of trials/observational and routine cohort patients Variable MIPA (n ¼ 221) Routine care Mean difference P-value Baranauskaite Toronto observational cohort (N ¼ 266) (95% CI) et al. MTX arm cohort (n ¼ 135) data (n ¼ 110)

Age, mean (S.D.), years 48.6 (11.5) 50.1 (14.4) 2.2 (–0.1, 4.6) 0.0574 41.2 (11.4) 46.85 (12.5) Female, n (%) 97 (44) 135 (51) — 0.131 50 (45) 51 (37) Disease duration, mean (S.D.), years 4.9 (7.5) 8.3 (8.0) 3.4 (1.9, 4.8) <0.001 3.25 (2.65) 12 (9.25) CRP, mean (S.D.), mg/l 13.3 (14.7) 10.8 (15.7) 2.4 (–0.4, 5.3) 0.0947 NS NS TJC, mean (S.D.) 12.8 (11.2) 6.9 (7.3) 5.8 (3.9, 7.7) <0.001 20.6 (12.3) 6.6 (6.9) SJC, mean (S.D.) 8.3 (7.9) 3.5 (3.7) 4.8 (3.6, 6.0) <0.001 14.7 (9.8) 4.3 (4.2) NS: not significant; SJC: swollen joint count; TJC: tender joint count. i94 Tuesday 28 April 2015 POSTER VIEWING I

suspected infection had a confirmed diagnosis of tuberculosis from in 11]. All patients with acute arthritis attained complete remission of biopsy tissue, 4% (n ¼ 3) had a diagnosis of sarcoidosis, 1 patient had joint symptoms by 6 months with NSAIDs; steroid (8/13), MTX (4/13), Behc¸ et’s. No crystal arthropathies were confirmed. 34% (n ¼ 27) of HCQS (1/13) and AZA (1/13) were additionally given for extra-articular patients had a diagnosis of undifferentiated arthritis where histology manifestations. Joint symptoms remained in remission at median 18 was non-specific for RA. Tissue quality and safety: 6 samples did not (IQR 6–43) months follow up. With respect to chronic arthritis, at contain a synovial lining layer and therefore could not be graded, but median follow up of 28 (IQR 10–48) months, 2/4 patients were in sufficient tissue was available for microbiology. No biopsies were complete remission with steroids (3/4), MTX (3/4) and HCQS (1/4). 1 complicated by infection or haemarthrosis. Patients with negative patient with ILD died due to supervening lung infection. biopsies did not go on to develop subsequent infection. Conclusion: Ankle is most commonly involved in sarcoid arthritis. Conclusion: US-guided synovial biopsy is a useful, minimally invasive Acute oligoarthritis is the commonest presentation with excellent tool that provides rapid tissue sampling and analysis. Additionally, in response to NSAIDs. our demographic area where there is high prevalence of TB, it is an Disclosure statement: The authors have declared no conflicts of important adjunct to rule out active infection prior to the initiation of interest. disease modifying therapy. The procedure is safe and well tolerated, allowing rheumatologists to make prompt diagnosis and management 111. ANTI-TNF THERAPY INDUCED ARTHRITIS IN PATIENTS decisions within the department. WITH INFLAMMATORY BOWEL DISEASE Disclosure statement: The authors have declared no conflicts of interest. Elizabeth Reilly1, Cathryn Edwards2 and Kirsten Mackay1 1Rheumatology, South Devon Health Care Foundation Trust and 2Gastroenterology, South Devon Health Care Foundation Trust, 110. ARTHRITIS IN SARCOIDOSIS Torquay, UK

1 1 1 Durga P. Misra , Abhra C. Chowdhury , Able Lawrence , Background: Paradoxical inflammation (PI) associated with anti-TNF 1 1 1 Amita Aggarwal , Ramnath Misra and Vikas Agarwal therapy treatment of various diseases has been reported. 1 Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Development of psoriasis is common in patients with IBD treated Medical Sciences (SGPGIMS), Lucknow, India with anti-TNF therapy (up to 22.5%) but musculoskeletal (MSK) symptoms are less frequently reported (1–2%). Background: Data on articular involvement in sarcoidosis is sparse in Methods: Thus, we explored the prevalence of arthritis which literature, with prevalence varying from 2.6% to 51%. We present data developed in patients with IBD following treatment with anti-TNF from our centre regarding patients with articular manifestations in therapy. We reviewed the clinical features, drug history, blood tests sarcoidosis. and radiology of these patients. Changes to biologic therapies were Methods: Case records of patients presenting to our centre from 2005 documented and local databases reviewed to assess local prevalence to 2014 with sarcoidosis were retrospectively reviewed. Diagnosis of of Crohn’s disease or ulcerative colitis. sarcoidosis was based on non-caseating granulomas negative for Results: Of the eight patients who developed MSK symptoms, all had acid-fast bacilli, fungal elements or foreign bodies (n ¼ 6) in lymph Crohn’s disease and seven were female (31–59 years, mean 46). Mean nodes, liver or skin or oligo- or polyarthritis with or without hilar time from diagnosis of IBD to start of anti-TNF therapy was 10.5 years adenopathy, erythema nodosum, uveitis or facial palsy (n ¼ 11). Joint (range 1–32 years). All were treated initially with infliximab and involvement was assessed clinically, with joint radiology performed in continued on this for a mean of 2.7 years (range 2 months to 5 chronic cases. It was further classified as acute or chronic depending years). Most (75%) were also treated with MTX. Mean time to MSK on duration of symptoms lesser or greater than 6 months. symptoms was 9 months (range 0–48 months). Infliximab was Results: Of 23 patients with sarcoidosis, 17 (74%) had features of joint switched to adalimumab (ADA) in 6 of 8 patients; 4 due to severe involvement (Table 1). Median age at presentation was 39 [interquartile MSK symptoms, 2 due to poor IBD control and 1 due to rash and hair range (IQR) 34.5–48] years, 10/17 were females. Median duration of loss. All noticed significant improvement in stiffness and pain with the symptoms at presentation was 3 (IQR 1–24) months. Acute oligoar- change of drug. Having switched from infliximab to ADA, 2 patients thritis was the commonest pattern of joint involvement; large joints then developed similar MSK symptoms with ADA (mean 1.8 years). were involved in 16 with 11 having ankle involvement. 15 had episodic Both discontinued ADA and their MSK symptoms resolved. All arthritis. 6 had Lofgren syndrome. 12 had fever, 6 had peripheral described early morning stiffness and arthralgia, 25% had synovitis, lymphadenopathy. Thoracic involvement was present in 14 patients 25% sacroiliitis and inflammatory back pain, 50% enthesitis and 25% [interstitial lung disease (ILD) in 5, hilar/mediastinal lymphadenopathy a lupus-like reaction (rash, RP, sicca, and development of ANA, dsDNA). Most experienced knee and MTPJ involvement (75%) with 50% describing elbow, wrist, MCPJ and PIPJ symptoms. One patient with drug-induced lupus required CYC treatment. The prevalence of PI 110 TABLE 1. Summary of articular and extra-articular features leading to MSK symptoms in patients with CD treated with INF in our Clinical characteristics Acute (n ¼ 13) Chronic (n ¼ 4) centre is 12.5% (see Table 1). This occurred despite co-prescribed Pattern of articular involvement MTX in most patients. Oligoarthritis 9 — Conclusion: Small joint polyarthralgia was the predominant MSK Polyarthritis 4 3 symptom. However, 25% developed SpA and 25% developed lupus- Dactylitis 0 1 like reactions. Stopping or switching agents appears of benefit. Course of arthritis Disclosure statement: C.E. has received honoraria from MSD, Episodic 13 2 AbbVie and Ferring. K.M. has received honoraria from MSD, UCB, Persistent — 2 AbbVie and Roche. The other author has declared no conflicts of Joints involved Knee 4 3 interest. Ankle 11 2 Metatarsophalangeal 1 1 Shoulder 2 2 Elbow 3 2 111 TABLE 1. Prevalence of IBD in Torbay Hospital and treatment with anti-TNF Wrist 3 3 therapy Metacarpophalangeal 1 — Prevalence Number Number treated Number with Proximal interphalangeal 1 — with IBD with infliximab paradoxical Enthesitis 1 — (over last 5 years) inflammation Extra-articular features Fever 10 2 CD 642 64 8 Peripheral adenopathy 3 3 UC 1071 8 0 Hilar/mediastinal adenopathy 9 2 IBD unclassified 103 2 0 Interstitial lung disease 5 — CD: Crohn’s disease; UC: ulcerative colitis. Erythema nodosum 7 2 Plaques/papules 1 1 Parotid enlargement 1 2 Hepatomegaly 2 — Splenomegaly 1 — Uveitis 1 — Facial palsy — 1 Peripheral neuropathy 1 — Optic neuritis 1 — POSTER VIEWING I Tuesday 28 April 2015 i95

112. PREGABALIN VERSUS AMITRIPTYLINE IN THE 113. RETROPERITONEAL FIBROSIS AND IGG4 DISEASE: A TREATMENT OF FIBROMYALGIA IN IRAQI PATIENTS SINGLE-CENTRE STUDY Sami Salman1, Samir Yousuf2 and Luma Eassa3 Shirish R. Sangle1, Pamela M. K. Lutalo1, Louise Nel1, 1Rheumatology, Medical College, 2Pharmacology, Medical College James Pattison2, Tim O’Brien3 and David D’Cruz1 University of Baghdad and 3Pharmacology, Medical College, 1Louise Coote Lupus unit, 2Renal Medicine and 3Urology, Guy’s and Baghdad, Iraq St Thomas’ NHS Foundation Trust, London, UK

Background: FM is a disorder characterized by widespread muscu- Background: A retrospective observational study of patients with loskeletal pain, tenderness and joint stiffness for longer than 3 months, IgG4 related disease and retroperitoneal fibrosis. accompanied by fatigue, sleep disturbances, memory and mood Methods: Retroperitoneal fibrosis (RPF) is a rare chronic inflammatory disturbances. Pregabalin is one of the approved therapies for this condition which may be associated with IgG4 disease. Thirty-nine condition. Our aim is to compare the efficacy and tolerability of patients diagnosed with idiopathic RPF were retrospectively analysed pregabalin to that of amitriptyline in the treatment of Iraqi patients at Guy’s and St Thomas’ Hospitals, London, England. All patients’ data suffering from FM. regarding clinical presentation, markers of inflammation, immunoglo- Methods: One hundred and twenty-three patients with FM fulfilling the bulin subsets, autoantibody profiles, imaging and histopathology was Wolfe 2010 criteria were randomized to amitriptyline in a dose of 25 mg collected. Comprehensive Diagnostic Criteria (CDC) for the diagnosis once daily (61 patients) or pregabalin in a dose of 75 mg once daily of IgG4 disease was applied to all patients. (62 patients) for a period of 12 weeks. Patients were followed up at Results: There were 24 Caucasian, 6 Asian and 9 Afro-Caribbean 4 weeks intervals; clinical improvement was assessed by calculating patients. There were 19 women and 20 men. The median age of the the patient’s scores at each visit according to Wolfe 2010 and patient was 54 (38–80) years. Eighteen patients had ureteric obstruc- Fibromyalgia Impact Questionnaire criteria. Blood samples were taken tion and 12 patients presented with renal failure. Eight patients had at the beginning of the study and at the end of the 12 weeks for the periaortitis; one had thoracic aorta involvement. One patient had false estimation of malondialdehyde and glutathion levels. aneurysm of common iliac artery and one other had lung cavities. One Results: Amitriptyline 25 mg/day and pregabalin 75 mg/day signifi- patient had history of treatment with methysergide. The median ESR cantly improved the symptoms of fibromyalgia. Improvement in the 28 (5–91) mm/h and CRP was 26 (6–200) mg/l. The median IgG levels pain score, wide pain index was significantly better with pregabalin were 12.3 (6.6–17.2) g/l, IgG1 levels 8.8 (3.8–15.2), IgG2 levels 4.2 than with amitriptyline (P ¼ 0.0001) at 4 weeks of treatment, but both (0.6–7.2), IgG3 levels 0.5 (0.1–0.8) and IgG4 levels 7.44 (0.05–23.7) g/l. drugs achieved comparable improvement at 8 and 12 weeks. The Twenty patients had raised immunoglobulin levels (12 IgG1 (>9.5), one sleep and somatic symptoms severity score (SSS), showed a highly IgG2 (>6.9) and seven had IgG4 (>1.11) g/l. All but two patients had significant difference (P ¼ 0.0001) in favour of pregabalin treatment at biopsies, seven of them had confirmed diagnosis (based on IgG4 4, 8 and 12 weeks, respectively. Improvement on revised fibromyalgia plasma cells and fibrosis) and four had probable diagnosis of IgG4 impact questionnaire total score was significantly more with pregaba- based on biopsy. None of the patients had positive serology for the lin than in amitriptyline throughout the 12 week study period. The effect ANA, dsDNA, ENA or ANCA antibodies. Twelve patients had ureteric of both drugs on oxidative status was shown by a significant elevation stents and two required nephrectomy. Twenty-eight patients received of the glutathione and reduction of the malondialdehyde levels CS and four patients received steroid sparing drugs such as AZA and (P ¼ 0.0001) produced by the two drugs at the end of 12 weeks. MTX in addition to CS. Twenty-eight (72%) patients had significant Amitriptyline was better tolerated than pregabalin. The main adverse improvement. One patient deteriorated but declined for B cell effects with amitriptyline were drowsiness and sleepiness, dry mouth depletion (rituximab) therapy. The median IgG4 levels after the and palpitation, while those reported with pregabalin were sleepiness treatment were 0.31 g/l. Fifteen patients had confirmed diagnosis of and weakness. IgG4 based on CDC criteria. Conclusion: Pregabalin was better than amitriptyline on the SSS and Conclusion: IgG4 disease may be considered in patients with sleep disturbances. Amitriptyline was better in patient compliance and retroperitoneal fibrosis and periaortic lesions. FDG-PET-CT imaging tolerability. is useful diagnostically and response to CS and immunosuppressant Disclosure statement: The authors have declared no conflicts of therapy is favourable. interest. Disclosure statement: The authors have declared no conflicts of interest. i96 Wednesday 29 April 2015 POSTER VIEWING II

between March 2012 and August 2014. The NICE criteria defining RTX use included: use in combination with MTX; previous inadequate BHPR AUDIT AND CLINICAL response to, or intolerance of, other DMARDs, including at least one EVALUATION anti-TNFa agent; pre-RTX DAS for 28 joints (DAS28) >5.1. Repeat DAS28 was performed 6 months post-RTX, with a re-treatment interval of no less than 6 months and re-treatment only if improvement in DAS28 1.2. 114. BLOOD PRESSURE IN SLE PATIENTS Results: Data were collected for a total of 128 RA patients (103 female and 25 male). Mean age was 61.2 years. 58% (n ¼ 74/128) patients Jyoti Bakshi1, Anisur Rahman1 and David A. Isenberg1 were taking MTX in combination with RTX compared with 57% in 1Rheumatology, University College London Hospital, London, UK 2012. 72% (n ¼ 92/128) patients had received at least one or more anti-TNFa agents prior to treatment with RTX compared with 80% in Background: Patients with SLE have an increased risk of developing 2012. Pre-treatment DAS28 assessments improved from 76% in 2012 cardiovascular disease (CVD) compared with healthy people of the to 87% (n ¼ 112/128). The same percentage of patients (90%) had same age and gender. In women between the ages of 35 and 44, the DAS28 >5.1 in both audits. 78% (n ¼ 100/128) patients had their presence of SLE increases the risk of developing CVD by 50 times. DAS28 checked post treatment, an improvement from 56% in 2012. Generic risk factors for CVD contribute to the CVD risk in patients with DAS28 was reduced by 1.2 in 81% of these patients compared with SLE. Hypertension is an important modifiable risk factor for CVD and is 80% in 2012. Akin to 2012, none of the patients had RTX at less than common in patients with SLE. The risk associated with increasing 6-monthly intervals. 53% of non-responders received further RTX blood pressure (BP) is continuous, with each 2 mmHg rise in systolic treatment (90% in 2012). blood pressure associated with a 7% increased risk of mortality from Conclusion: This national re-audit has shown an improvement in DAS ischaemic heart disease and a 10% increased risk of mortality from assessments (both pre and post-RTX treatment). More patients are stroke. National Institute for Clinical Excellence (NICE) guidelines for having their treatment discontinued if they don’t respond to RTX. The the general population suggest that if the clinic blood pressure is most common reasons for not prescribing concurrent MTX in 42% of 140/90 mmHg, 24-h ambulatory blood pressure monitoring (ABPM) is patients were adverse events and inefficacy. Previous malignancy, indicated. We assessed blood pressure measurements in patients with interstitial lung disease and positive lupus serology were the most SLE under the care of the Lupus Clinic at UCLH to assess how many common reasons in 28% of the patients who did not receive anti-TNFa would need to be referred for ABPM under these guidelines. treatment prior to RTX. Although recording of DAS28 has improved, Methods: We studied the clinic records for the last three consecutive there is still room for improvement. We can achieve this by making it appointments of 172 patients fulfilling ACR criteria for SLE. We part of the routine assessment of RA patients. We have disseminated recorded blood pressure measurements, concomitant use of anti- these results to all rheumatology units in Wales, and hope to continue hypertensive drugs and indications for prescribing those drugs. to improve our practice according to NICE guidelines. Patients who had not been seen in the last year were excluded. We Disclosure statement: The authors have declared no conflicts of defined raised blood pressure as 140/90 mmHg according to the interest. NICE guidelines. Results: Of the 172 patients studied, 153 (89%) were women. Fifty- seven per cent of patients were Caucasian, 18% Afro-Caribbean, 17% South Asian and 8% other ethnicity. Average age of all patients was 48 116. TOOLS FOR LIFE: A GROUP EDUCATION PROGRAMME years. Seventy-four patients (42%) with an average age of 54 years FOR PATIENTS WITH INFLAMMATORY ARTHRITIS: RESULTS were identified as having one or more elevated BP recordings and 36 OF AN AUDIT of these patients had two or more consecutive readings of elevated Gemma M. A. Brown1, Ayshea R. Glover1, Natalie A. Cooper1, BP. Though the majority (57/74) of these patients were on anti- Samantha L. Fitter2 and Rainer Klocke3 hypertensive medication, 17/74 (23%) were not treated and might 1Therapy Department, 2Clinical Audit Department and 3Department benefit from ABPM. Anti-hypertensive drugs were prescribed for of Rheumatology, Dudley Group of Hospitals, Dudley, UK hypertension (61%), LN (33%), pulmonary hypertension (4%) and CCF (2%). Of 35 patients prescribed anti-hypertensives for hypertension, 21 Background: The therapy department at Dudley Group of Hospitals (60%) still had elevated BP. have developed a group-based education programme for patients with Conclusion: CVD is an important cause of disability and death in SLE. inflammatory arthritis, named Tools for Life (TFL), to provide a more We have identified a large number of SLE patients with elevated blood efficient way to deliver knowledge and physical activity than our pressures who would potentially be eligible for ABMP monitoring. This previous 1:1 approach. The programme runs for four-weekly sessions includes both untreated and under-treated patients whose BP 140/ of 90 min, covering techniques and practical advice to apply to 90 mmHg. Based on these findings we are setting up a service locally to activities of daily living, relaxation, pacing skills plus a functional refer these patients for 24-h ABMP and create a pathway for initiating exercise programme. treatment. A target-based approach by modifying risk factors may result Methods: Clinically referred patients with inflammatory arthritis were in a reduced burden of cardiovascular disease in SLE patients. invited to take part in the programme by letter and information leaflet. Disclosure statement: The authors have declared no conflicts of The Joint Protection Knowledge Assessment (JPKA; Hammond and interest. Lincoln, 1999) questionnaire (score range 0–40; higher scores reflecting higher knowledge) and a timed functional exercise circuit 115. RITUXIMAB IN THE TREATMENT OF RHEUMATOID were completed before and after attending the programme. The ARTHRITIS: AN ALL WALES RE-AUDIT exercise circuit consists of eight functional exercises and two rest stations, lasting 60 seconds each. A patient satisfaction questionnaire Syed F. Bari1, Fazal Sheikh2 and Anurag Negi1 was completed on the final session. 1Rheumatology Unit, University of Wales Hospital, Cardiff and 2Peter Results: Of 61 patients agreeing to be booked onto the programme, Maddison Rheumatology Centre, Llandudno General Hospital, 43 (70.5%) attended the first session, and 32 (74.4%), median age 62 Llandudno, UK (range 31–85), attended at least three sessions and completed JPKA and the exercise circuit at baseline and 4 weeks. The mean baseline Background: A national audit was undertaken across all of the score for these participants for the JPKA was 28.4 (S.D. 5.1) points and rheumatology centres in Wales to assess adherence to National the timed exercise circuit was 157.2 (S.D. 38.9) repetitions. We found a Institute for Clinical Excellence (NICE) guidance (TA195) for treatment mean improvement in the JPKA of 4.1 (S.D. 4.6) points (P < 0.001, of RA patients with rituximab (RTX) in 2012. The results were published paired t-test), and in the timed exercise circuit of 19.5 (S.D. 37.7) as an abstract at the 2013 British Society for Rheumatology repetitions (P < 0.01). This programme required 12 h therapist time, conference. The main recommendation was to improve the DAS compared with 25 h it would require for the equivalent education to be assessments. We have re-audited our practice to assess improvement delivered via 1:1 treatment for each patient. All patients responded in the areas highlighted in the initial audit. agree/strongly agree when asked whether they benefitted from the Methods: Data were collected from each rheumatology centre in sessions; and whether they felt confident to self-manage their Wales for all RA patients who received their first RTX treatment condition following the programme. POSTER VIEWING II Wednesday 29 April 2015 i97

Conclusion: This audit suggests that our Tools for Life group 118. BASELINE PATIENT CHARACTERISTICS AND education programme is able to improve knowledge and functional TREATMENT FROM AN AUDIT OF TREAT TO TARGET physical fitness and is popular with patients. Although no previous RECOMMENDATIONS FOR RHEUMATOID ARTHRITIS: outcome data for 1:1 treatment are available to compare the INTERIM RESULTS effectiveness, the group-based programme required less therapist Maya Buch1, David T. O’Reilly2, Tom Sheeran3, Sarah Keidel4 and time than 1:1 treatment. A challenge remains to retain patients booked 1 to attend the full programme. Paul Emery 1NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Disclosure statement: The authors have declared no conflicts of 2 interest. Teaching Hospitals NHS Trust, Leeds, Department of Rheumatology, West Suffolk NHS Foundation Trust, Bury St Edmunds, 3Department of Rheumatology, Mid Staffordshire NHS 117. COMPLIANCE WITH TREAT TO TARGET Foundation Trust, Staffordshire and 4Medical Affairs, AbbVie Ltd, RECOMMENDATIONS ON RHEUMATOID ARTHRITIS AND Maidenhead, UK PATIENT OUTCOMES: INTERIM RESULTS OF A UK MULTICENTRE STUDY Background: RA is a considerable burden in the UK, with a Maya Buch1, David T. O’Reilly2, Tom Sheeran3, Sarah Keidel4 and prevalence of around 400 000 in the adult population. Treating patients Paul Emery1 early and appropriately may lead to better patient outcomes. In 2010, 1NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds international recommendations on treating to target were developed to Teaching Hospitals NHS Trust, Leeds, 2Department of improve RA management, and in 2012 a national audit was launched Rheumatology, West Suffolk NHS Foundation Trust, Bury St to assess progress against these standards. Edmunds, 3Department of Rheumatology, Mid Staffordshire NHS Methods: From April 2012, newly diagnosed patients with RA have Foundation Trust, Staffordshire and 4Medical Affairs, AbbVie Ltd, been recruited prospectively into the audit in 38 UK National Health Maidenhead, UK Service hospitals with rheumatology centres. Each patient was followed for a period of 1 year from initial presentation with data on Background: In 2010, therapeutic recommendations on treating to disease history, management and outcomes being collected. target, based on strong evidence and expert opinion were developed Descriptive statistics on patient characteristics and treatments at to improve RA management. The aim of this ongoing prospective baseline were calculated for this interim analysis. multicentre audit is to assess the impact of compliance with the Results: Baseline data were collected for 1158 [398 (34%) male] recommendations on RA patient outcomes over time. patients. Mean (S.D.) age at diagnosis was 58 (14.9) years. Patients Methods: Patients with newly diagnosed RA at presentation to 38 UK waited a median of 1.97 [interquartile range (IQR) 0.82–5.01] months National Health Service rheumatology clinics are being recruited to this from symptom onset to general practitioner presentation, 0.23 (IQR prospective, ongoing audit from April 2012 for 1 year follow up from 0.00–1.05) months from presentation to referral, 1.12 (IQR 0.59–1.77) diagnosis. Data on disease history, management and outcomes are months from referral to first rheumatologist visit and 0.0 (IQR 0.00– collected at each visit. We present interim results from cohorts of 0.76) months from first rheumatologist visit to diagnosis. 75.4% patients who have reached 6 and 12-months on compliance with the (n ¼ 873) of patients had a baseline DAS for 28 joints [DAS28; mean recommendations and patient outcomes. 4.81 (S.D. 2.40)], varied between geographical locations from 2.91 (S.D. Results: By August 2014, 1158 patients in 38 centres had been 1.55) to 5.42 (S.D. 0.90); 26% (n ¼ 300) had a baseline HAQ-DI [mean 1.2 (S.D. 0.8)]. 70% (n ¼ 809) of patients were commenced on DMARDs entered into the audit. Mean age at diagnosis was 58.4 years (S.D. 14.9). 314 patients (34% male) had both baseline and 6 month DAS for (most commonly MTX, n ¼ 694/1158, 60%), with 46% receiving a single DMARD, 24% receiving 2 and 1% receiving 3. 74% (n ¼ 856) 28 joints [DAS28; mean 4.71 (S.D. 1.49) and mean 3.12 (S.D. 1.39), respectively], and 99 patients (29% male) had both baseline and 12 were on steroids at baseline. Number of DMARDs per patient at baseline differed between locations, with between 0–73% receiving month DAS28 scores [mean 4.56 (S.D. 1.38) and mean 2.75 (S.D. 1.35), respectively. At 6 months, 129 (41%) achieved DAS28 < 2.6 and 51 none, 10–96% receiving 1, 1–70% receiving 2 and 0–25% receiving 3, (16%) achieved DAS28 2.6-<3.2; at 12 months, 53 (54%) achieved as did number of non-DMARDs, with between 6–54% receiving none, DAS28 < 2.6 and 15 (15%) achieved DAS28 2.6–<3.2. At 6 months, 46–92% receiving one 0–13% receiving two and 0–1% receiving three 95.2% of patients were compliant with recommendation 1 Conclusion: This large cohort of patients was similar to the UK (Documented baseline target for treatment), 88.9% with recommenda- population of RA patients in gender distribution and age at diagnosis. tion 2 (Documented target of clinical remission [clinical remission, Most patients had been prescribed DMARDs and/or steroids at DAS28 <2.6]), 57.1% with recommendation 3 [Target of low disease baseline, as would be expected in patients with high disease activity in activity (LDAS) (DAS28 > 2.6-<3.2)], 89.2% with recommendation 4 secondary care. The longest contributor to the time between symptom (Informed of treatment target), 99.7% with recommendation 5 onset and first rheumatologist visit was patient-attributable suggesting (Informed of treatment strategy), 80.9% with recommendation 6 that education and awareness campaigns should be targeted at (DAS28 at each visit), 31.8% with recommendation 7 (If working, patients in order to reduce the delay in DMARD therapy and improve functional impairment recorded at each visit), 80.9% with recommen- outcomes. Overall the mean DAS28 score between regions showed dation 8 (Measure of disease activity at least every 3 months) and little variation, suggesting patients are accessing secondary care at 53.9% with recommendation 9 (change to therapy if target not met). similar levels of disease severity across geographical locations. The Conclusion: The results show an increase in compliance with wide variability in DMARD prescribing suggests that guidelines may be recommendations over time in this large real world population. In needed to optimize therapy for patients at diagnosis. particular, the high proportion of patients having a DAS28 at each visit Disclosure statement: M.B. has received honoraria from AbbVie; and (recommendation 6) is likely to have positively impacted the observed has received meeting sponsorship from AbbVie. T.S. has received improvement in remission. Mean DAS28 scores improved from consultancy fees from Roche, AbbVie, Novatis and Pfizer. S.K. is an baseline to 6 months and from 6 to 12 months. Achievement of employee of AbbVie and may receive company shares. P.E. has DAS28 < 2.6 improved over time. Achievement of DAS28 2.6 < 3.2 received consulting fees from AbbVie and has undertaken clinical trials months remained similar at both time points. This could be due to for AbbVie. The other author has declared no conflicts of interest. smaller patient numbers in the 12 month cohort or could reflect the more resistant disease in those given a target of DAS28 2.6-<3.2. 119. NURSE-LED BIOLOGIC INFUSIONS ARE SAFE AND Compliance with the majority of recommendations was high at 6 EFFECTIVE months. Of note is the lower compliance with recommendation 9, change to treatment if remission not achieved, which is likely to reflect Sandini Wijeweera1, Nikki Day1, Owen A. Moore1, Jonathan King1, a newly diagnosed population with visit intervals which are too soon to Lindsay Robertson1 and Ognjenka Savanovic-Abel1 fully assess the response of treatments. 1Rheumatology Department, Plymouth Hospitals NHS Trust, Disclosure statement: M.B. has received honoraria from AbbVie; and Plymouth, UK has received meeting sponsorship from AbbVie. T.S. has received consultancy fees from Roche, AbbVie, Novatis and Pfizer. S.K. is an Background: Rheumatology Nurse Specialists play a vital role in employee of AbbVie and may receive company shares. P.E. has management of patients with inflammatory arthritis and CTD. Their role received consulting fees from AbbVie; and has undertaken clinical includes DMARDs counselling and monitoring, administration of trials for AbbVie. The other author has declared no conflicts of interest. biologics and assessment of patients prior to the infusions. i98 Wednesday 29 April 2015 POSTER VIEWING II

The Rheumatology Nurse Specialists in Plymouth recently started 121. RHEUMATOID ARTHRITIS ANNUAL REVIEW IN carrying outpatient assessment prior to biologic infusions. This was PRIMARY CARE initiated to overcome problems with infusion bookings experienced in Bethan Forgie1,2, Angela Earl1, Raad Makadsi2, Sian Griffith2 and the infusion ward [Planned Investigation Unit (PIU)]. The department 3 found that because of demands from the acute medical take patients’ Toby Garrood 1Greystone House Practice, Redhill, 2Department of Rheumatology, infusions were postponed or cancelled with increasing frequency. This 3 sometimes resulted in patients not getting the infusions within the East Surrey Hospital, Redhill and Department of Rheumatology, required time duration. Guy’s and St Thomas’ NHS Foundation Trust, London, UK Methods: We ran a pilot programme of nurse-led infusions in the planned investigation unit in Derriford Hospital from April to August Background: National Institute for Clinical Excellence guidelines 2014. Rheumatology nurse specialists (RNS) assessed the patients in recommend that all patients with RA undergo annual review to the PIU on the same day of infusion before starting the infusion. This assess disease activity and to screen for comorbidities. Integrated was done by filling out a checklist by the RNS with the information care between secondary and primary care is key to this process. This provided by the patient. This checklist was formulated in consensus was reflected in the 2012–2013 Quality and Outcomes Framework with all rheumatologists in the department. The checklist covered all (QOF), which included the requirement to establish a register of all RA safety issues related to biologics. These included observation of vital patients, although specific indicators for assessing cardiovascular risk signs recorded by the PIU nurses (temperature, heart rate, pulse rate, and bone health were retired for the 2014–2015 framework. Here we report our experience of a pilot RA annual review clinic run in primary blood pressure and O2 saturation), recent infections, new breathing problems, recent surgery, recent blood investigations and excluding care. pregnancy where applicable. First the lead RNS was trained by the Methods: All RA patients registered to the practice were sent rheumatology registrar, and then the other RNS were trained by the invitations to come to a nurse-led clinic. Those accepting were lead. After the initial assessment if a problem was encountered, then asked to attend for a blood test 2 weeks prior to the 20-min the RNS would contact a member of the medical team to clarify it. appointment. Clinical data including medication, blood results, BMI, Results: In total, 64 patients were seen by RNS in a 5-month period. blood pressure, smoking status, alcohol intake, pulse rate and rhythm RNS were able to identify the patients whom had safety issues and were uploaded onto the EMIS medical template using a pre-written were not suitable for infusions. Three patients were identified as unsafe protocol. Patients were also assessed for signs of depression and to proceed with the infusions as they had planned or had offered an annual influenza vaccination. QRISK2 and FRAX scores recent surgeries and unhealed wounds. None of the patients who had were recorded and high-risk patients were referred to a general infusions had complications. Before nurse-led biologic infusions practitioner as were patients requiring additional medical input. around 20 patients’ infusions were postponed in a month. All of Patients were also assessed for signs of depression and offered an these 64 patients were seen by the RNS at times when there was no annual influenza vaccination. junior medical cover for the PIU. And all these infusions would have Results: Out of a total list of 11 000, 48 RA patients were identified. 34 been postponed at least by two weeks had there been no RNS cover. of these attended the clinic. The average age was 61 years: 29 were Conclusion: Nurse-led biologic infusions are safe and effective way female and 28 were on disease-modifying therapy. Three patients had for biologic infusions. This minimizes patient cancellations and established CVD and did not undergo a QRisk calculation. Ten improves patient consistency with the infusions. patients had a QRISK2 score of 20% or greater 10 year risk. Of these, Disclosure statement: The authors have declared no conflicts of six required lifestyle discussion, two were started on a statin, one was interest. started on aspirin and one needed treatment for hypertension. Six patients were already on a bisphosphonate. FRAX assessment identified a further 12 at higher risk requiring DXA, of whom 3 were 120. PREVALENCE AND MICROBIOLOGICAL found to have low BMD requiring bisphosphonate treatment. No CHARACTERISTICS OF INFECTED FOOT ULCERS IN patients were found to have depressive symptoms requiring further PATIENTS WITH RHEUMATOID ARTHRITIS intervention. Conclusion: RA is associated with increased risk of a number of Pauline Fitzgerald1, Heidi J. Siddle2, Michael J. Backhouse3 and comorbidities. However, screening is not always reliably coordinated E. Andrea Nelson4 between primary and secondary care. Despite the loss of risk 1Rheumatology, Harrogate District Hospital, Harrogate, 2Foot Health assessment indicators from the current QOF it is essential that Department, Leeds Teaching Hospitals NHS Trust, 3Leeds Institute patients requiring additional treatment are identified and treated early. of Rheumatic and Musculoskeletal Medicine, University of Leeds and We have found that a nurse-led clinic in primary care has good uptake 4School of Healthcare, University of Leeds, Leeds, UK by patients. This approach is cost-effective, quick and reliable and can help ensure that an integrated care approach can help to optimize Background: The objective of the study was to estimate the long-term treatment for RA patients. prevalence of suspected infection in foot ulcers of patients with RA, Disclosure statement: The authors have declared no conflicts of describe the microbiological characteristics and investigate risk interest. factors. Methods: Retrospective clinical data were collected for all patients attending a rheumatology foot ulcer clinic during a 15-month period: wound swab data were collected from those with suspected infection. BHPR Clinical Prize Results: Twenty-eight patients with RA and foot ulcers were identified; eight of these patients had suspected infection and wound swabs 122. NURSE-LED ANNUAL REVIEW SERVICE FOR STABLE INFLAMMATORY ARTHRITIS taken (29%). There were equal men and women, with median age 74 1 1 1 years, and average disease duration 22 years. Cardiovascular disease Fidelma Gordon , Jananath Wijeyekoon , Spencer Ellis and Thiraupathy Marianayagam1 and peripheral vascular disease (CVD and PVD) were reported in six 1 patients (n ¼ 6), diabetes in two patients. Six patients were treated with Department of Rheumatology, East and North Herts NHS Trust, DMARDs; three were on biologic medications and two on steroids. Hertfordshire, UK Five wound swabs cultured skin flora, one Staphylococcus aureus, one had no growth after culture; and one was rejected due to labelling Background: In response to demands on rheumatology outpatient error. services at East and North Herts Trust, an opportunity to reconfigure Conclusion: Almost a third of people with RA and foot ulcers services, addressing delayed appointments while improving quality of attending clinic over one year had suspected infection, however care, was recognized. An annual review service was designed and microbiological analysis failed to isolate pathogens in six of seven initiated for patients with stable inflammatory arthritis. Compliance with wound swabs. This may be due to inaccurate diagnosis of ulcer National Institute for Clinical Excellence (NICE) CG79 recommenda- infection or to issues with sampling, collection, transport, analysis or tions for RA was audited. reporting. There were insufficient data to relate risk of suspected Methods: Six hundred patients seen by a senior nurse practitioner infection with risk factors. Further research is required to identify the reducing 10% of follow-up appointments for consultants in 2013. The most appropriate techniques for infection diagnosis, wound sampling nurse consultations were template based, following criteria estab- and processing. lished in NICE CG79 Guidance. Fifty patients (n ¼ 50) with RA were Disclosure statement: The authors have declared no conflicts of randomly selected. Data collected included: assessment of disease interest. activity, damage, functional measurements, comorbidities and poten- tial complications of RA. Cross referral with multidisciplinary teams, POSTER VIEWING II Wednesday 29 April 2015 i99

surgical needs and assessment of social, psychosexual and employ- GPs and Consultants updating them of patient status. Finally, a gap in ment issues were considered. patient assessment was revealed, only 29% enquired about extenuat- Results: Overall 41/50 had no tender joints and 35/50 no swollen ing social and psychological issues. joints. DAS 28 ranged from 1.6 to 3.36, with 34/50 in remission (DAS 28 Conclusion: The audit has found fundamental components of <2.6). 15/50 had low disease activity scores of 2.6–3.2. 1/50 had a patients’ rights, and care aren’t meeting the appropriate standards. moderate score of 3.36. None had high disease activity. 28/50 were on Although this service clearly provides patients with access to medical MTX (monotherapy or combination), 17/50 were on alternative support, various areas for improvement have been highlighted. Staff DMARDs while 5/50 were not on DMARDs. Treatment dosage was training and responsibilities should be updated and reflected in not altered in 33/50, while escalation was recommended in 7/50. All policies respectively to ensure the highest level of care is obtained. those not on a DMARD stayed off therapy and 5/50 reduced dose. In a bilingual country, the needs of Welsh speakers and additionally the Cardiovascular assessment highlighted 16/50 with QRISK2 <20%. Of literately disabled (i.e. hearing and sight impaired) should be met. the 12/50 with QRISK2 >20%, none were on statins, 2/12 had known Finally, the recording and documentation skills of staff should be hypertension, 4/12 de novo hypertension. BMI ranged from 17 to 44.4 enhanced. The conclusions drawn from this audit are to be circulated (median 26.4) for all 50 patients. Osteoporosis assessment using to the rheumatology departments involved, along with suggestions to FRAX, identified 18/50 requiring DXA, with 6/18 new diagnoses of overcome the identified shortcomings. osteoporosis, 7/18 osteopenia and 5/18 normal results. 41/50 did not Disclosure statement: The authors have declared no conflicts of require a new multidisciplinary team referral. 2/50 had iritis. 2/50 had interest. chronic obstructive pulmonary disease and 7/50 had mild breathless under investigation. 16/50 were still working while 32/50 had retired. 1/ 124. ONE CENTRE’S EXPERIENCE OF THE USE OF 50 worked reduced hours due to arthritis. 1/50 did not feel able to COMBINATION THERAPY WITH METHOTREXATE AND work. 36/50 had no issues with depression and 5/50 were already LEFLUNOMIDE FOR PATIENTS WITH INFLAMMATORY treated for depression. 9/50 had mild work or home related depressive ARTHRITIS symptoms. Conclusion: Nurse-led annual reviews facilitate detailed assessment Katie Patterson1, Ashley Hawarden1,2 and Andrew Hassell1,3 for patients with RA which are time-consuming (40 min), but give 1School of Medicine, Keele University, 2Trauma and Orthopaedics, greater autonomy to both patient and nurse. Reducing treatment for University Hospital of North Midlands and 3Staffordshire those in remission was possible as well as escalation for those with Rheumatology Centre, Haywood Hospital, Stoke-on-Trent, UK active disease. Time to reflect on psychosocial issues, comorbidities and complications of RA led to important actions, particularly Background: Combination therapy, particularly involving MTX, is detecting osteoporosis. Nurse-led annual assessments enabled routine in the treatment of inflammatory conditions and evidence consultants to review more complex patients while simultaneously suggests more favourable outcomes, particularly for RA, when enhancing the quality of follow-up reviews. Patients have adequate compared with monotherapy. One such combination is MTX and time to discuss their global health needs. This model’s success has LEF, for which there has been evidence of efficacy but minimal data on seen the nurse-led annual review clinic become a cornerstone of our toxicity. In this study we report our experience of treating 189 patients outpatient service. with inflammatory disease using this combination over the last 12 Disclosure statement: The authors have declared no conflicts of years in our centre. interest. Methods: All patients treated with second-line therapy within our service are entered on to a bespoke, in-house computer monitoring programme, the diagnostic and monitoring database (DIAMOND). 123. ALL WALES RHEUMATOLOGY ADVICE LINE AUDIT: DIAMOND was searched for all patients who had received MTX plus RHEUM TO IMPROVE LEF combination therapy up to the present date. Patients included in Debora J. Harry1, Sarah J. Evans1 and Amanda C. Hill1 the analysis were those with any rheumatological condition who had 1Rheumatology, Hywel Dda University Health Board, Llanelli, UK received this combination, without receiving other DMARDS or biological therapy concurrently. Basic demographic and diagnostic Background: Advice line services provide patients with a clinical point details were recorded from DIAMOND, supplemented by clinical of contact for symptomatic complaints, medication queries and details from patient letters (for those who stopped therapy). In addition, general guidance on their condition while at home. The nurse-led in instances of serious adverse occurrences, the patient clinical notes telephone service aids the management of long-term conditions, were scrutinized. giving the patient a sense of control over their disease while offering Results: 189 (59 male, mean age 61.18 years, range 25–89 years) the opportunity to speak to a healthcare professional. In turn, this patients received the combination. For most the primary diagnosis was service can alleviate pressures on clinic and general practitioner (GP) RA. 6 patients had no formal diagnosis recorded and were excluded. appointments. Guidelines from the Royal College of Nursing support Overall average duration of combination therapy was 389.01 days staff and ensure the highest level of care is provided to the patient via (range 7–1797 days). 138 patients (74.41%) discontinued therapy, 20 advice line and voicemail messaging services. due to lack of efficacy (mean length of therapy 401.87 days) with 66% Methods: A prospective, audit was undertaken to assess rheumatol- of these discontinuing in less than 12 months. 110 stopped due to ogy advice line services in Wales. The audit was performed in a adverse events, mainly gastrointestinal disturbances or deranged liver questionnaire format created against guidance from the 2006 function (mean length of therapy 386.67 days). Of the remainder, three publication Royal College of Nursing – Telephone Advice Lines for discontinued due to inter-current illness, two for family planning, two People with Long-term Conditions. Questionnaires were sent to each due to management change and one secondary to lack of compliance. rheumatology department in Wales and collected over a 2-month Three discontinued following severe pulmonary symptoms: one period. developed dyspnoea after 11 weeks; combination therapy was Results: Twenty-one questionnaires were returned, assessing 10 stopped and symptoms rapidly resolved with investigations showing standards of care against current guidance. Staff have access to no clear evidence of pneumonitis or infection. A second patient patient information via computer systems and medical case notes. developed a classical pneumonitis after 35 weeks. They responded to Hence, sufficient patient details were available to address a patient’s withdrawal of combination therapy and systemic CSs. A third patient concerns/queries. Areas of excellence were evident for patient developed cough and dyspnoea after 4 weeks. This patient deterio- reassurance and medical advice. The assessed standard, call content, rated and died despite cessation of combination therapy, broad proved the most adherent to guidance. Overall, the advice line service spectrum antibiotics, systemic CSs and full supportive therapy. Post helps resolve medical issues, while offering self-management gui- mortem was inconclusive (drug-induced pneumonitis was felt to be the dance and further instruction for worsening problems. Nevertheless, most likely cause of death). No patient had suffered a pneumonitis the audit also identified problems. Whereby 85% of staff confirmed when on (usually MTX) monotherapy. advice line services are detailed in their job description, only one Conclusion: MTX plus LEF combination therapy in routine clinical department confirmed knowledge of a Health Board policy and only practice represents a useful option in the management of inflammatory 23% centres had a local protocol defining staff responsibilities for this arthritis. The incidence of side effects is significant although the vast service. In addition, just 61% of staff were up-to-date with statutory majority are self-limiting. Care is required with respect to the possibility training. Additional failings include language and disability barriers, of the combination causing potentially life threatening pneumonitis. poor maintenance of confidentiality and documentation of consent. Disclosure statement: The authors have declared no conflicts of Furthermore, only 50% of calls were followed with correspondence to interest. i100 Wednesday 29 April 2015 POSTER VIEWING II

125. IDENTIFYING PATIENTS PREFERENCES REGARDING Previous research has shown the programme is more effective and EDUCATION SESSIONS FOR SELF-MANAGEMENT OF NEWLY cost-effective than usual care, has sustained benefits, is popular with DIAGNOSED RHEUMATOID AND INFLAMMATORY ARTHRITIS patients and therapists and reduces healthcare costs. Wide imple- mentation would enable many more people to benefit from the Yvonne Hough1, Ann M. Clayton1, Debbie Lenton1, 1 1 1 programme. Describing the programme through a website and Catherine Singleton , Elaine Williams , Angela J. Cox , Julie facilitating access to the resources required to deliver the programme K. Dawson1, Adrian R. Clewes1 and Rikki E. Abernethy1 1 might accelerate its adoption and spread. The report describes the Rheumatology, St Helens and Knowsley Teaching Hospitals NHS process used to produce the website, and the content and format of Trust, Merseyside, UK the resultant website. Methods: Web developers and physiotherapists who devised Background: The National Institute for Clinical Excellence Standards of ESCAPE-pain developed a prototype website that described the Care for RA recommend that educational sessions are offered to patients content, format and practicalities of delivering ESCAPE-pain, with attending the early arthritis clinic (EAC) within 1 month of diagnosis. downloadable resources. Focus groups and think aloud interviews Historically our unit has offered these sessions and patient feedback has were held with 19 people (11 physiotherapists). Their likes, dislikes, been very positive, but recent sessions have been poorly attended. preferences and difficulties navigating the website were recorded, Evidence supports improving patients’ understanding of arthritis and its analysed, summarized and feedback to the web developers who management through educational activities and self-management pro- revised the website. grammes. The aim of this study was to gain patient opinions on education Results: A website has been produced that enables healthcare sessions, barriers for attending and views on content. professionals to deliver ESCAPE-pain by describing the programme Methods: All patients who attended the EAC over a 2-month period and contains videos of the programme’s exercise and education were asked to complete a questionnaire following their appointment. 60 components in action; all downloadable resources required to deliver questionnaires were distributed and 31 returned (response rate of 52%). the programme; clinical outcomes measures, patients satisfaction Results: Although all patients had been invited to sessions, when survey; spreadsheets to evaluate the programme; PDFs of the asked only 29% could remember being invited, 10% were unsure and research evidence-base behind the programme; and conduits to 61% did not remember being invited. Of the 29% who said yes 56% feedback to create networks to swap information and experiences to attended a session. Reasons given for non-attendance were split enhance the programme. The website, resources and permission to between personal circumstances and convenience. 86% of all the deliver the programme is free. The website is available at www.es- patients felt the education sessions could be beneficial, with Table 1 cape-pain.org showing the usefulness of topics. An opportunity to comment on Conclusion: The information and resources available at www.escape- perceived benefits was given, common themes identified; peer pain.org will enable healthcare professionals to deliver an evidence- support, increased understanding for family members, developing based rehabilitation programme for chronic joint pain. This will coping strategies, self-management of their condition including pain facilitate wider clinical implementation, so that many more people management. 47% of patients said they would prefer the education can benefit from the programme. over 2 sessions, with 27% preferring it over 8 and the remainder giving Disclosure statement: The authors have declared no conflicts of no preference. Preference for time of day was 34% morning session, interest. 28% early evening and 24% afternoon, 14% gave no preference. Patients were asked to identify barriers to attending, shared themes included work, family commitments and transport. Conclusion: A total of 52% of patients participated in the ques- 127. CURRENT PRACTICE OF BONE MINERAL DENSITY tionnaire. The following recommendations were identified; having ASSESSMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS written information within the EAC including an invitation for partners AND EVALUATION OF OPRA: A NEW OSTEOPOROSIS or next of kin to attend; the education sessions clearly advertised on PREDICTION TOOL the department noticeboard and within the biannual newsletter in a 1 1 2 timely manner to encourage self-referral and enable patients to plan Stefanie Lip , Elaine Morrison , Stuart H. Ralston and 1,2 their personal commitments around the sessions. The results support Barbara Hauser 1 our existing programme content and timing of sessions reflects Department of Rheumatology, Southern General Hospital, Glasgow 2 patients’ needs with suggestions for a reminder service and the and Rheumatic Diseases Unit, Institute of Genetics and Molecular option for a guest speaker. Medicine, University of Edinburgh, Edinburgh, UK Disclosure statement: The authors have declared no conflicts of interest. Background: Osteoporosis (OP) and fragility fractures are recognized complications in RA. The risk of OP is doubled in RA patients compared with healthy controls. National Institute for Clinical 125 TABLE 1. How patients rated usefulness of topics Excellence and SMC guidelines recommend to monitor RA patients for the development of OP but fail to give clear guidelines when and Not at all Slightly Useful, % Extremely useful, % useful, % useful, % whom to assess from the RA population. A new OP Prediction (OPRA) tool has recently been published in order to facilitate and improve OP Effects of arthritis 3.5 3.5 37 56 Looking after joints 0 7 41 52 risk assessment in RA. Our aim was to examine current practice of Managing fatigue 0 14 29 57 BMD assessment in an RA population within a rheumatology centre in Patient speaker 9 0 39 52 South of Glasgow. We further tested the accuracy of OPRA in Managing pain 0 4 34 62 detecting OP when applied to RA patients who had a DXA scan over Managing a flare up 0 7 31 62 the last 10 years. Benefits of exercise 11 4 48 37 Methods: Clinical records on RA patients who attended the Outpatient Healthy eating 7 7 48 37 Rheumatology Clinic were reviewed from March 2014 to May 2014. Understanding blood results 7 0 37 57 Info about medication 0 0 34 66 Data on age, gender, height and weight, disease duration, presence or Info about arthritis 0 0 39 61 absence of BMD assessment over preceding 10 years and DXA outcome were collected. OP risk was assessed and scored using the OPRA model. Results: There was a total of 265 patients where the majority were female (81.1%, n ¼ 215). The mean age was 63.4 12.5 years, with a 126. DELIVERING ESCAPE-PAIN: AN ONLINE GUIDE FOR mean disease duration of 15.9 10.3 years. A large proportion did not HEALTHCARE PROFESSIONALS have a BMD assessment for at least 10 years prior to data collection (202, 76.2%). The OPRA model was implemented for 132 patients 1 2 2 3 Mike Hurley , Andrea Carter , Desmond Carter , Lonan Hughes , (where data were available) and it deemed 82.6% (109) patients at 3 4 Aoife Ni Mhuiri and Nicola Walsh medium to high risk of OP (OPRA score 3 and above) of whom only 51 1 School of Rehabilitation Sciences, St George’s, University of (38.9%) had a DXA scan of spine or hip. When testing the OPRA model London, 2Musculoskeletal Programme, Health Innovation Network on patients with known OP 126 RA patients were classified to be at risk South London, UK, 3Salaso, Health Solutions, Limerick, Ireland of OP resulting in a 95.7% sensitivity of the model. and 4Allied Health Sciences, University of the West of England, Conclusion: Only the minority of patients with RA have been checked Bristol, UK for OP despite many patients being at high risk of OP. OPRA is a simple useful tool in identifying patients at risk of OP and could be Background: Enabling Self-management and Coping of Arthritic Pain implemented easily into routine clinical practice. through Exercise (ESCAPE-pain) is a programme that integrates Disclosure statement: The authors have declared no conflicts of patient education, self-management, coping strategies and exercise. interest. POSTER VIEWING II Wednesday 29 April 2015 i101

128. DIGITAL VASCULOPATHY IN SCLERODERMA: describes the outcomes of all ARD patients attending this service FEASIBILITY AUDIT OF A NURSE-LED RAPID ACCESS during a 5-year period. DIGITAL ULCER CLINIC TO IMPROVE PATIENT CARE Methods: A retrospective analysis was carried out of all ARD patients attending a monthly Rheumatology-Obstetric clinic at UCLH between Tanaka Ngcozana1, Voon H. Ong2 and Christopher P. Denton2 1 2 Jan 2010 and Oct 2014. Data extracted included: rheumatological Rheumatology, Hillingdon NHS Foundation Trust and Centre of diagnosis; disease activity (by clinician judgement); medication Rheumatology and Connective Tissue Diseases, Royal Free NHS change; current and previous pregnancy history; treatment; blood Foundation Trust, London, UK results and pregnancy outcomes. Results: A total of 228 patients referred from UCLH and surrounding Background: Digital ulcers (DUs) are an important vascular complica- hospitals were seen in 433 consultations in the study period. The tion of scleroderma (SSc). The burden of DUs has been widely diagnoses included: SLE and lupus-like disease (n ¼ 67), RA (n ¼ 60), reported and these patients are more likely to access health services JIA (n ¼ 40), AS (n ¼ 23), PsA (n ¼ 22), biomechanical pain (n ¼ 4) and frequently. The aims of this study were to examine the role of a chronic and soft tissue abnormalities (n ¼ 12). There were 222 women specialist nurse-led DU clinic in assessment of these patients and to and 6 men with a mean age of 33.8 years. Reasons for consultations contrast their care prior to referral to this clinic. included pre-pregnancy counselling (n ¼ 129, 6 men and 123 women), Methods: A nurse-led rapid access DU clinic was established in July assessment of disease activity during pregnancy (n ¼ 258) and post- 2012. 21 unselected patients from July 2013 to January 2014 were partum review (n ¼ 46). Disease activity was judged to be mild in 98 invited to complete a baseline questionnaire at first attendance and an and moderate in 22 patients in pre-pregnancy counselling, mild in 142 exit questionnaire on discharge from the clinic. They were followed up and moderate in 32 patients during pregnancy, and mild in 15 and over variable period (at least a month) during which DUs were actively moderate in 2 patients at post-partum review (time period January managed in the clinic. The baseline questionnaire assessed detailed 2013 and October 2014). Drugs most commonly discontinued at pre- history of DU including complications (critical ischaemia, infection, pregnancy review included MTX and the TNF inhibitors, rituximab, gangrene) and management of DU and access to medical care prior to bisphosphonates and colchicine. The drugs most commonly con- DU clinic (frequency of GP visits and A&E attendances, unscheduled tinued during pregnancy were HCQ, SSZ, steroids, AZA, NSAIDs and appointments).The exit questionnaire examined patient experience low-dose aspirin (at onset of third trimester). In 64 patients for whom related to DU clinic (waiting time, duration of consultation, frequency of pregnancy outcomes were available, there were 3 spontaneous first visits, satisfaction with quality of care) and management (treatment, trimester miscarriages and 99 live births (42 vaginal and 12 assisted advice provided and self-management). vaginal deliveries and 38 patients had caesarean section), with an Results: The majority of the clinic attendees (61%) were 56 years of average gestation of 39.6 weeks and birth-weight of 2.8 kg. Maternal age and above. 76% were women. The duration of DU disease history complications included pre-eclampsia and urological problems. No was variable (7months to 40 years).Prior to DU clinic attendance, 71% maternal/fetal deaths/congenital defects reported. patients reported that their DUs were primarily managed by rheuma- Conclusion: The majority of complex pregnant patients who attended tologist but 10% commented paucity of medical care for DU. UCLHs combined Rheumatology– Clinics during January Management of DU was variable with topical dressings and systemic 2010 and October 2014 received effective surveillance during pre- approaches with antibiotics and surgical intervention. 90% received pregnancy and during pregnancy, which led to successful pregnancy up to six courses of antibiotics for DU. Among the respondents 76% outcomes. had attended the Accident and Emergency Department due to the Disclosure statement: The authors have declared no conflicts of ulcers, 90% had unscheduled appointments and a similar proportion interest. required review with their GPs.90% required hospital admissions for management of DU. For the exit questionnaire, patients were reviewed at variable intervals as judged on clinical need; a majority were 130. THE SURVEY OF RHEUMATOLOGY OCCUPATIONAL reviewed monthly. All patients were advised on wound management, THERAPY COMPRESSION GLOVE PRACTICE AND skin care, optimization of medications (vasodilators, antibiotics) and PROVISION IN THE UK self-management. Only two patients had emergency admission during Yeliz Prior1 and Alison Hammond1 follow up. All patients were satisfied with the services provided 1Centre for Health Sciences Research, University of Salford, including consultation time, waiting times, information regarding DU Manchester, UK care and wound dressings. They reported that their needs in personal care of DU were met and the establishment of the clinic is justified and Background: Compression gloves are provided by rheumatology valuable. occupational therapists (OTs) in routine clinical care to people with Conclusion: Our study confirmed the significant burden of DU early or established RA. They are prescribed for day and/or night wear, for patients and healthcare services. A dedicated specialist nurse-led to reduce hand pain and stiffness and improve function. However, we DU clinic may improve medical care in DU and empower patients know little about the size, extent and mechanisms of rheumatology OT in self-management. Our study suggests that this novel strategy compression glove provision in the NHS. may offer a cost-effective approach to improved management of DU Methods: An online survey of the College of Occupational Therapists in SSc. Specialist Section for Rheumatology (COTSSR) members’ compres- Funding statement: This work was supported by a research grant sion glove practice and provision in the UK was conducted (n ¼ 82). from Actelion Pharmaceuticals. Paper questionnaires were posted to those who could not access the Disclosure statement: The authors have declared no conflicts of online questionnaire. No personally identifiable data were collected. interest. The data collected were primarily quantitative although participants were encouraged to provide additional comments. 129. A RETROSPECTIVE ANALYSIS OF OUTCOMES FROM A Results: 60 Rheumatology OTs (73%) completed the survey (band 5, SPECIALIST INTERDISCIPLINARY RHEUMATOLOGY- 2; band 6, 30; band7, 23; band 8 and over, 5). Most responders OBSTETRICS CLINIC provided compression gloves to patients with early and established RA (n ¼ 52 and n ¼ 49). One in three Rheumatology OTs stated Hanh Nguyen1, Sean Knight1, David J. Williams2 and Ian P. Giles1 compression glove provision was based on patients’ clinical needs 1Department of Rheumatology and 2Maternal and Fetal Medicine, (e.g. presence of symptoms such as hand pain, joint swelling, early University College London Hospital NHS Foundation Trust, London, morning stiffness) rather than their diagnosis. The commonest brand UK issued was Isotoner; 90% of gloves were three-quarter length and 10% were full-finger length. Most (75%) provided compression gloves Background: Autoimmune rheumatic diseases (ARDs) such as SLE to early RA patients prior to the use of DMARDs, and 61% provided and RA commonly affect women of childbearing age and require gloves to patients stable on DMARDs but with continuing hand treatment with medication that may adversely affect pregnancy. There symptoms. On average, rheumatology OTs issued 10 (S.D. 8.5) gloves/ is an increased risk of adverse pregnancy outcomes associated with month to patients with RA (early and established combined). Nearly active disease in patients with RA and SLE. The question of disease three-quarters (73%) provided replacement gloves without charge management in these patients during pregnancy and breastfeeding when the first gloves issued wore out. One in four OTs did not issue presents challenges for clinicians. Close collaboration between replacement gloves, instead providing patients with glove manufac- interdisciplinary teams of rheumatologists and obstetricians is required turers’ details in order to purchase replacement gloves themselves. to provide optimal management of patients with ARD pre-conception, Conclusion: Compression gloves are commonly provided to people during pregnancy and post-partum to help prevent adverse pregnancy with early and established RA, and other symptomatic hand conditions outcomes. Currently however, there are very few combined by rheumatology OTs in the National Health Service (NHS), including Rheumatology-Obstetrics services in the UK. One such service patients’ prior to and on stable regimens of DMARDs. Although this exists at University College London Hospital (UCLH) and this report survey provided useful insight about compression glove practice and i102 Wednesday 29 April 2015 POSTER VIEWING II

provision by rheumatology OTs in the UK, the sample was drawn from 64%. 62 of 102 patients (60.8%) had their cholesterol checked since the COTSSR members, and may not be representative of wider diagnosis. The remaining 40 (39.2%) patients have never had rheumatology compression glove practice in the NHS. cholesterol levels checked. Of those 40 without cholesterol being Disclosure statement: The authors have declared no conflicts of checked, 27 had not had it done at least 5 years since diagnosis. The interest. total average cholesterol of patients who had it checked was 4.6. In total 24 patients in the audit were on a statin and 88 were not. The average cholesterol of those not on a statin was 4.9. There were 22 131. THE IMPACT OF THE EARLY ARTHRITIS CLINIC ON patients not on a statin whose cholesterol was above 5.0. Of these, OUTCOMES IN RHEUMATOID ARTHRITIS: A CLINICAL AUDIT only two were commenced on a statin after the cholesterol was Divya Raj1, Fiona Wu1 and Frances Humby1 checked. 1Rheumatology, Barts and the London School of Medicine, London, Conclusion: The audit demonstrates that there is failure to adhere to UK guidelines as set out by BSR with a significant proportion of patients with RA not having had their cholesterol checked. A significant number Background: Studies in RA increasingly demonstrate that earlier of patients whose cholesterol was above 5.1 were not on a statin. This therapeutic intervention (<16 weeks) is associated with a greater audit therefore shows that not only are patients not having their likelihood of reaching drug-free remission. The Barts Health early cholesterol checked appropriately, but they are also not being arthritis clinic (EAC) was established in 2008, aiming to accelerate prescribed a statin when needed. Some recommendations for diagnosis and treatment delivery in suspected inflammatory arthritis improving clinical practice could include presenting the results of patients. We audit and compare the time to DMARD initiation from RA this audit at our local audit meeting, including a footnote on clinic onset in new patients attending the EAC and the general letters informing GPs to ensure annual assessment of CVD risk in Rheumatology Clinic in Mile End Hospital in relation to the 3 months these patients and sending a blood form for fasting cholesterol with the target [2009National Institute for Clinical Excellence (NICE) guidelines]. RA annual review appointment letter. Patterns of biologic drug prescription and current day remission status Disclosure statement: The authors have declared no conflicts of were additionally investigated. interest. Methods: Between 2008 and 2012, all new RA patients attending the EAC were identified, while a 1-month sample (February) of new RA patients attending the general rheumatology clinics were identified. 133. SAFETY AND EFFICACY OF CERTOLIZUMAB Data were collected from the onset of RA until October 2014, including COMPARED WITH OTHER ANTI-TNF AGENTS IN gender, age, diagnosis date, time to DMARD, DMARD type, time to RHEUMATOID ARTHRITIS PATIENTS TREATED AT BUCKS first biologic, biologic type and remission status. Data collection was HEALTHCARE TRUST done as part of a departmental audit and no ethical approval was Shilpa Selvan1, Malgosia Magliano1 and Jackie Hall1 required. 1Rheumatology, Stoke Mandeville Hospital, Buckinghamshire, UK Results: 89% of patients attending the EAC (n ¼ 59) were initiated on DMARDS within 3 months, while only 50% of RA patients attending Background: Certolizumab pegol (CZP) has been shown to be general rheumatology clinics (n ¼ 69) achieved the NICE target for efficacious in the treatment for RA. Despite a randomized controlled DMARD therapy. The mean time to DMARD initiation in the EAC (2.12 trial reporting that CZP has a similar safety profile to other anti-TNF months, range 1–7 months) was shorter than that of new patients agents, we have observed that a high proportion of our patients attending the Rheumatology clinics (4.22 months, range 1–18) with treated with CZP developed infective complications. We conducted a statistical significance (P ¼ 0.0003). 67% of EAC patients received retrospective observational study of the safety of CZP compared with MTX first-line (single or combination). A smaller proportion of EAC other anti-TNF alpha agents to compare the rate of infective patients were prescribed Biologics compared with Rheumatology complications among RA patients treated with CZP, adalimumab clinic patients (30% vs 40.6%) meanwhile the EAC remission rate on (ADA), etanercept (ETA) and golimumab (GOL); to characterize the 2014 follow up was higher (24.18% vs 16.9%). type of infections; and to identify risk factors for infections. Conclusion: The institution of the EAC in Mile End Hospital Methods: This study was a retrospective review of patient case notes. substantially increased success in achieving the NICE target for All patients treated with anti-TNF for RA between January 2011 and DMARD therapy in RA patients compared with regular clinics. June 2014 were identified. Fisher’s exact tests were used to Furthermore, better disease control and higher remission rates statistically analyse risk factors that increase infection rates. following early DMARD therapy can be linked to a lowered frequency Results: 81 notes were obtained; females: 61 (75%), males: 20 (25%), of biologic prescription in this clinic group. with mean age of 64 years. The mean RA duration was 10.3 years; 59/ Disclosure statement: The authors have declared no conflicts of 81 (73%) were RF positive and 43/81 (53%) were anti-CCP antibody interest. positive; and 6/81 (8%) were current smokers. The mean number of DMARDs that patients had been on was 2.6. 23/81 (29%) patients 132. AUDIT OF CHOLESTEROL MEASUREMENT IN previously had biologics. 23 patients were treated with CZP, 45 with PATIENTS WITH RHEUMATOID ARTHRITIS ADA, 37 with ETA and 4 with GOL. 10 patients on CZP, 2 on ADA, 1 on ETA and none on GOL developed infections. All 10 patients developed Edward Sames1, Heather Paterson1 and Charles Li1 infections within the first 20 months of treatment. Patients on CZP 1Rheumatology Department, Royal Surrey County Hospital, Surrey, developed the following infections: eight, respiratory (three pneumo- UK nia, five lower respiratory tract); one, infected finger cyst; and one intra-abdominal abscess. One patient on ADA developed leg cellulitis Background: Strong evidence exists that RA is an independent and one a respiratory tract infection, and one patient on ETA cardiovascular (CV) risk with excess CV burden persisting after developed periorbital cellulitis. No patients on GOL developed adjustment for traditional risk factors resulting in increased morbidity infections. Seven patients who developed infections on CZP had and mortality. In 2009 the British Society for Rheumatology (BSR) concomitant respiratory comorbidities (bronchiectasis, chronic published guidelines stating that patients with RA should undergo a CV obstructive pulmonary disease and asthma), three required hospital assessment at their annual review. Joint British Society guidelines admission and one required Intensive Treatment Unit admission. CZP suggest an optimal total cholesterol level of <4.0 mmol/l, but suggest was discontinued in six patients due to severe infections. The rate of an acceptable audit level would be <5 mmol/l. Annual systemic comorbidities in patients who developed infections was higher screening and regular audit of treatment targets were recommended compared with those who did not. Factors including concomitant as a result DMARDs, steroids, seropositivity and smoking were similar across the Methods: We created a database of current patients with RA by groups, and comorbidities in patients treated with other anti-TNFa examining the clinic letters of patients in the rheumatology department agents were also similar to those of the CZP cohort. Pre-existing lung and randomly selecting patients with a definite diagnosis of RA. In total disease was found to be the only statistically significant risk factor 102 RA patients were analysed. We collected the following data: associated with the development of infections. This was not found to Patient age, RF and anti-CCP antibody, CVD risk factors, whether the be relevant to other anti-TNF agents. patient was already on lipid lowering therapy and the patient’s Conclusion: In our patient cohort, we observed a higher rate of registered general practitioner (GP) surgery. Patient’s blood results infective complications in patients treated with CZP compared with were searched using Winpath to ascertain whether cholesterol levels other anti-TNFa agents. Patients who developed infective complica- had been checked. tions in the CZP group had a higher rate of pre-existing lung disease. Results: Of the 102 patients in the audit 76% were RF positive and The rate of comorbidities was found to be higher in the CZP group 74% were anti-CCP antibody positive. The age range was between 21 compared with other biologics. and 91 and the average age was 65. The ratio of females to males was Disclosure statement: The authors have declared no conflicts of 3:1. The proportion of patients with additional risk factors for CVD was interest. POSTER VIEWING II Wednesday 29 April 2015 i103

134. ADHERENCE TO NATIONAL CERVICAL CANCER when the standards were set. Most patients were satisfied with their SCREENING PROGRAMME IN SYSTEMIC LUPUS care, and greater QS adherence led to better patient satisfaction. ERYTHEMATOSUS IN EAST LONDON Hence, there should be a greater emphasis to meet these standards, for instance by reducing new-patient waiting times and offering more Amana A. Sharif1, Siama Yousaf1, Angela Pakozdi1 and Dev Pyne1 1 support regarding employment. The introduction of a template for Rheumatology, Royal London Hospital, Barts Health NHS Trust, rheumatology referrals for GPs can help triage patients more London, UK effectively and thus, improve waiting times. Patients could have dedicated sessions with rheumatology specialist nurses including Background: There is an increased prevalence of cervical cancer addressing their employment/mood. Alternatively, there can be a among SLE patients. Although SLE may be an independent risk factor checklist/template to remind doctors to have education sessions for for cervical cancer, the use of immunosuppressive medications is also new patients and annual holistic reviews for all RA patients. A re-audit contributory. Our aim was to investigate adherence to cervical cancer should be performed after these suggestions have been implemented screening in our SLE population. to determine any improvement. Methods: SLE patients aged 25–50 years, attending tertiary care Disclosure statement: The authors have declared no conflicts of centre lupus clinics were asked to complete a questionnaire related to interest. cervical cancer screening. Adherence to National Institute for Clinical Excellence (NICE) guidelines on cervical cancer screening was assessed. NICE recommends 3-yearly screening for patients aged 136. PURSUING BEST PRACTICE TARIFFS: THE REALITIES 25–49 years, 5-yearly for ages 50–65 years and for patients above 65 IN RHEUMATOLOGY years if they had not been screened before. Laura Tucker1, Amarnath Marthi1, Ursula Perks1 and Results: 66 SLE patients aged 25–50 years returned the question- Malgorzata Magliano1 naire; the median age was 38 (interquartile range 33–43). 28 patients 1Rheumatology, Buckinghamshire Healthcare NHS Trust, Aylesbury, (42%) were Asians (Bangladeshi, Indian or Pakistani), 20 (30%) were Caucasians, 11 (17%) were black and 7 (11%) were other (mixed race UK or oriental Asians). Only 41 patients (62%) had a cervical screening test in the past 3 years. Overall, 27 (45%) reported 3-yearly, 4 (7%) Background: In early inflammatory arthritis (EIA) there is evidence to reported 2-yearly and 6 (10%) had annual screenings. 12 patients suggest that early referral to secondary care and early treatment with (20%) had never had a cervical cancer screening test. Caucasians and DMARDs improves outcomes. To reflect this, EIA was recently Blacks showed a poorer adherence to screening compared with included in the government’s payment-by-results scheme with best Asians (n ¼ 10, 50% and n ¼ 5, 39% vs n ¼ 8, 29%, respectively, practice tariffs (BPTs) in the diagnosis and treatment of patients P ¼ 0.412). 7 patients (12%) had abnormal test results, but no patient suspected of EIA, DMARD therapy and biologic therapy. was diagnosed with cervical cancer in this cohort. An additional 30 Methods: We retrospectively audited our practice at a local level aged above 50 years were asked if they had ever had a screening test, against these criteria over a 6-month period and assessed the time of these 6 patients (23%) had not. from symptom onset to referral and from referral to actual clinic Conclusion: Adherence of SLE patients to our national cervical cancer appointment. screening programme seems to be lower than that of the general Results: Of the 238 patients assessed, we found that 96 patients were population. The lowest adherence rate is observed in Caucasians. considered to have a diagnosis of EIA at the first clinic appointment, Raising awareness through patient education is essential as SLE with 45 patients requiring further investigation. By 12 months from the patients have an increased risk of developing cervical cancer. initial clinic appointment: 107 patients were diagnosed with EIA and Disclosure statement: The authors have declared no conflicts of 131 patients were diagnosed with non-IA conditions. Median time to interest. referral from symptom onset was 180 days, but there was a significant difference between those with EIA and those without (120 days vs 270 days, P ¼ 0.0012). 19 patients were excluded from this analysis due to insufficient data (9 in the EIA group and 10 in the non-EIA group at final 135. AN AUDIT OF CURRENT CLINICAL PRACTICE IN THE diagnosis). We found that only 38 patients of the 107 patients with a RHEUMATOLOGY DEPARTMENT OF UNIVERSITY HOSPITAL final diagnosis of inflammatory arthritis (35.5%) were referred within a WALES AGAINST THE TOP TEN QUALITY STANDARDS FOR 90 day period and thus, in reality, even fewer patients would meet the RHEUMATOID ARTHRITIS AS DEFINED BY THE BRITISH BPT guideline requiring DMARDS to be commenced within 3 months SOCIETY FOR RHEUMATOLOGY of symptom onset: patients with suspected EIA should be assessed in Evan Sun1, Anurag Negi2 and Ruth Davies2 an outpatient clinic within 3 weeks of GP referral. The median time for 1School of Medicine, Cardiff University and 2Rheumatology this BPT was found to be 50 days for the entire cohort. Patients with an Department, University Hospital Wales, Cardiff, UK eventual diagnosis were seen significantly sooner than patients who did not go on to develop EIA in the first year (median time 43 days vs Background: RA is a chronic disabling disease with an inflammatory 53 days, P ¼ 0.0089). We found that only 29 (13.9%) of all patients cause characterized by synovitis and joint-destruction. While there is would have met this criterion: 17 with EIA and 12 found not to have no cure for RA, it can be well controlled by DMARDS and biological EIA. 94 patients (52 in the EIA group) were seen within 6 weeks of therapy. The aim of treatment is disease remission and to reduce referral and of the 92 patients who were commenced on DMARDs comorbidity. The British Society for Rheumatology laid out the Top Ten within the first year, only 24 patients received them within the 6-week Quality Standards for RA in January 2012. This audit investigates both window. the quality of care received by patients with RA in the University Conclusion: Despite the majority of patients being diagnosed with EIA Hospital of Wales (UHW) against this standard, and investigates at first clinic appointment, delays involved in referral to rheumatology correlation between patient satisfaction and adherence to these assessment prevented the attainment of many of the BPT targets. guidelines. Thus interventions focusing on clarity of referrals to secondary care, Methods: In 107 patients with RA a retrospective analysis was optimizing methods of triage and appropriate use of early arthritis performed from medical notes. A patient survey was also conducted in clinic appointments may improve the timely assessment of patients these patients in the outpatient clinic, with no extra visits required. presenting with early inflammatory arthritis. Results: Of the 107 patients recruited, 89 were referred before 2012, Disclosure statement: The authors have declared no conflicts of 18 after. UHW performed well in quality standards 5, 7, 8 and 10 such interest. as providing information and opportunities to ask questions regarding RA (92%), providing a suitable frequency (78%) and location (89%) for 137. MEETING BEST PRACTICE TARIFFS: A NEED TO appointments and offering biologic therapy if the patients met the OPTIMIZE THE REFERRAL PATHWAY IN INFLAMMATORY National Institute for Clinical Excellence criteria (100%). Areas for ARTHRITIS improvement include standards 1, 2, 3, 4, 6 and 9, in particular waiting time for the first rheumatology appointment (41%), reviewing DAS Amarnath Marthi1, Laura Tucker1, Ursula Perks1 and scores monthly (37%) and offering support regarding work (27%). Malgorzata Magliano1 However, there was a trend towards improvement after Jan 2012 when 1Rheumatology, Buckinghamshire Healthcare NHS Trust, Aylesbury, the standards were set. The majority (89%) of patients were satisfied UK with the care they received. There was a positive correlation between adherence to quality standards and patient satisfaction. Background: Early inflammatory arthritis (EIA) was recently included in Conclusion: While this audit shows that UHW performed well in the the government’s payment-by-results scheme with best practice patient satisfaction component of the audit, the standard set at 100% tariffs (BPTs) in the diagnosis and treatment of patients suspected of compliance was not met for most quality standards, and there is scope EIA, DMARD therapy and biologic therapy. Having identified relatively for improvement. There was a trend towards improvement after 2012, poor performance in meeting these criteria, we hoped to assess i104 Wednesday 29 April 2015 POSTER VIEWING II

137 TABLE 1. Referral criteria mentioned and number of patients diagnosed with EIA at the initial clinic Synovitis Morning Boggy Small joint Positive Raised 6 weeks, n stiffness, n swelling, n involvement, n squeeze test, n CRP/ESR, n Y 38 55 37 118 8 85 NA 176 174 184 100 224 114 N 24 9 17 20 6 39 IA when Y in referral 26 25 22 57 7 48 IA when N in referral 9 4 4 10 2 12 NA: not mentioned; N: not present; Y: present.

potential areas of delay. Delays may be introduced in symptom onset administration, and patients were interviewed regarding effects on to primary care assessment; assessment to referral in secondary care; menstruation. and referral to actual appointment. At a local setting, we retro- Results: Ten patients received CYC therapy, nine had SLE and one spectively assessed potential factors that may contribute to compo- had granulomatosis with polyangiitis (GPA). The average age was 29 nent 3: the analysis and subsequent triage of referrals to secondary (range 19–39) years and laboratory markers of disease were care. manifest by average dsDNA level of 277 IU/l in patients with SLE Methods: Of 742 referrals for new patients in a 6-month period, we and ANCA positivity plus a CRP of 110 mg/dl in GPA. Sixty per cent identified 251 referrals suggesting a potential diagnosis of early (6/10) were offered ovarian protection. The remaining 4/10 patients inflammatory arthritis. Of these, referral data were available for 238 were older and/or receiving emergency rather than elective treat- patients. We assessed the time from referral to initial clinic appoint- ment. Half (3/6) of the patients offered GnRHa agreed to treatment ment, the content of the referral letter and any investigations (aged 26, 27 and 30 years). The cumulative CYC dose ranged from performed in the community that were accessible to the rheumatol- 500 mg to 6.75 g. In 8/10 (80%) patients their menstrual cycle was ogist at the time of the referral. Content was assessed by identifying regular prior to starting treatment and 4 patients developed irregular key clinical features that are known to be associated with a diagnosis menstrual cycle post treatment for a minimum of 9 months. Only of early inflammatory arthritis: unexplained synovitis for > 6 weeks; one of the four patients who developed irregular menstrual cycles early morning stiffness >30 min; boggy (soft tissue) swelling of 2 received GnRHa. Of six patients who expressed a desire for future joints; involvement of small joints of hands, feet or wrists; positive pregnancy, two were offered ovarian protection, one of whom metacarpal or metatarsal squeeze and mentioning raised CRP and accepted GnRHa. ESR. These were marked as present (Y), not mentioned (NA) and Conclusion: Our study period was too short to identify POF in our mentioned but not present (N). patients but, given the young age and low total cumulative dose of Results: There were significantly shorter referral to clinic times in GnRHa, the relative risk is low. This might explain why not all women patients who went on to be diagnosed with an inflammatory arthritis. A were offered and/or accepted ovarian protection. Based on these potential cutoff score of two criteria or more showed poor sensitivity findings we propose to develop guidelines to discuss fertility risks with and specificity in this dataset. The most common criteria to be patients in a more systematic and transparent fashion with clear mentioned by referrers were small joint involvement and raised documentation of decision-making based on patient age, planned total inflammatory markers (CRP and ESR), but rarely did they mention cumulative dose of CYC and patient wishes. the presence or absence of a positive squeeze test (Table 1). Although Disclosure statement: The authors have declared no conflicts of many referrers carried out basic assessment of haematology, interest. inflammatory markers, RF and anti-nuclear antibodies, very few tested for anti-CCP antibodies (even with confirmed small joint 139. SURVEY OF PATIENTS SWITCHING TO I.V. involvement). ZOLEDRONATE FOR OSTEOPOROSIS SUGGESTS BETTER Conclusion: This audit suggests that the use of a proforma requiring INFORMATION DELIVERY MAY BE NEEDED: RESULTS FROM assessment of clinical features may obtain more clinically relevant A QUALITY IMPROVEMENT PROJECT information from the referrer. We hope close collaboration with referrers to educate and clarify these pertinent features will improve Jane Stratton1, Laura Bromilow1 and Sreekanth Vasireddy1 and streamline referrals on re-audit and meet BPT targets. 1Department of Rheumatology, Bolton NHS Foundation Trust, Disclosure statement: The authors have declared no conflicts of Bolton, UK interest. Background: As part of a Quality Improvement (QI) project in 138. HOW ACCEPTABLE IS OVARIAN PROTECTION TO our department in 2012, quarterly i.v. ibandronate and pamidronate WOMAN OF CHILDBEARING AGE TREATED WITH were discontinued for osteoporosis treatment. Patients on these CYCLOPHOSPHAMIDE: EXPERIENCE AT A SINGLE CENTRE were reviewed before discontinuation using a structured QI process involving a rheumatology pharmacist and a consultant rheumatologist. Sabrina Valentino1, Maria Mouyis1 and Ian Giles1 Those having continuing indication for i.v. bisphosphonate were 1Rheumatology, University College London Hospitals, London, UK switched to annual zoledronate after being given information via telephone or in clinic, and the resulting cost-savings and clinical Background: CYC is an effective treatment to induce remission in practice improvements were reported by us previously. These patients severe cases of several rheumatic conditions, including SLE and have now all received at least one zoledronate infusion. Our aim was to vasculitides. CYC therapy however, has adverse effects including explore these patients’ experience of switching to zoledronate. gonadal toxicity. There is an increased risk of premature ovarian Methods: 75 patients were identified from the project, 46 of whom failure (POF) with administration of CYC, particularly with increasing went on to have zoledronate. A questionnaire was designed to include maternal age and total cumulative dose of CYC. Treatment with a experience of information received, convenience, side effects and gonadotropin-releasing hormone agonist (GnRHa) has been shown overall satisfaction. 5-point Likert scales were used for ratings. to reduce POF in women given i.v. CYC and is often used in Patients were surveyed via telephone. Where not contactable on first patients requiring chemotherapy with CYC. Guidelines on call, one more attempt was made. Data were processed in Microsoft GnRHa and its acceptability in women of childbearing age in Excel. rheumatology are lacking. We surveyed the use of GnRHa in women Results: Contact with 42 patients was attempted (4 had died), contact with rheumatic disease receiving i.v. CYC during a 1-year period at was made with 28 patients (60%) and 19 completed the survey (40%). University College London Hospital. When asked, How satisfied were you with the information you Methods: All female patients of childbearing (defined by the World received?, 44% were satisfied (S) or very satisfied (VS), 22% were Health Organization as 15–49 years) age who received i.v. CYC at unsatisfied or very unsatisfied and 22% couldn’t remember. There was UCLH between 1 January 2013 and 31 December 2013 were wide variation in patients’ understanding of why the switch was made, included. Demographic data were collected including age, diag- with reasons including less cost, more effective, licensing and nosis, cumulative dose of CYC and markers of disease activity in convenience. 50% experienced at least one side effect with the form of CRP, anti-dsDNA and ANCA. It was noted from medical zoledronate. 72% of patients were S or VS regarding convenience of records whether patients were counselled regarding potential new arrangements, 11% were unsatisfied (0% very unsatisfied). 58% ovarian failure and offered ovarian protection prior to CYC were S or VS, 22% were unsatisfied or very unsatisfied with the POSTER VIEWING II Wednesday 29 April 2015 i105

process of switching to zoledronate (11% not rated). When asked, Overall, how satisfied are you with the new annual infusions compared with the previous quarterly infusions?, 56% were S or VS, 22% were BHPR RESEARCH: QUALITATIVE unsatisfied or very unsatisfied (17% not rated). Conclusion: Although 72% of patients found zoledronate to be more convenient, 22% were unsatisfied or very unsatisfied with the process of switching and overall with zoledronate compared with previous 141. A PATIENT AND PUBLIC INVOLVEMENT GROUP STUDY infusions. Although all patients were given verbal information before ON THE USABILITY OF THE MYJOINTPAIN.ORG WEBSITE the switch via telephone or in clinic, 22% could not remember this and Naomi Algeo1, Jo Adams1, Ainslie Cahill2, Chris Dickson2 and 22% were not satisfied with the information received. While the David Hunter3 numbers were too small to correlate any drug side effects with the 1Faculty of Health Sciences, University of Southampton, Arthritis patient experience ratings, this survey suggests the possibility that, Research UK Centre of Excellence for Sport, Exercise and despite verbal information, a subgroup of patients may need further 2 Osteoarthritis, Southampton, UK, Arthritis Australia and counselling as to the purpose and benefits of a treatment switch. We 3Rheumatology, The Mater Hospital, Sydney, Australia therefore recommend that in treatment switching QI scenarios a structured framework is used where verbal information is supplemen- Background: There are an estimated 4.7 million with knee OA and 2.1 ted with printed information with a contact number for any subsequent million with hip OA in the UK. Resources to manage OA within the queries. National Health Service are limited. National Institute for Health and Care Disclosure statement: The authors have declared no conflicts of Excellence guidelines advocate education and self-management for all interest. people with OA. Most recently, e-health programmes via the internet are being used to deliver health services and information. Arthritis Australia & 140. DEVELOPMENT OF A DENOSUMAB DATABASE WITH Osteoarthritis Research Society International developed Myjointpain.org CLINICAL AND AUDIT/QUALITY IMPROVEMENT to support Australians in self-managing hip and/or knee joint pain. There FUNCTIONALITY: RESULTS FROM A TECHNOLOGY is currently no equivalent UK e-health resource. This study explored the EXERCISE attitudes, facilitators and barriers towards using e-health by people self-

1 1 1 managing hip/knee OA in the UK. Mohannad Ammori , Beverley Travers , Laura Bromilow and Methods: A qualitative design using semi-structured telephone inter- Sreekanth Vasireddy1 1 views was used. Patient and public involvement (PPI) members were Department of Rheumatology, Bolton NHS Foundation Trust, recruited via Nottingham City Hospital. PPI members were included if Bolton, UK they had hip and/or knee joint pain and internet access. Each PPI member was provided with an information sheet and consent form. All Background: Denosumab is used for osteoporosis treatment. The consenting members received a link to the Myjointpain.org website Medicines and Healthcare products Regulatory Agency recommends and given seven days to practice using the programme. Participants that denosumab should not be used in patients with hypocalcaemia. were then contacted for a telephone interview. The interviews were Rare drug-related anaphylactic reactions have also been reported. It is transcribed and a six step thematic analysis used. This included given in our department as a course of six injections at 6-monthly reading/re-reading of transcript; coding interesting features of data; intervals over 3 years. Our patient database was on an MS Excel categorizing codes into potential themes and subthemes; reviewing spreadsheet. This had minimal audit functionality and no clinical themes; defining themes; and producing a final report. Themes functionality to indicate the next due date: our service target is to identified were independently verified. deliver repeat injections within a month of due date. Database Results: Twelve PPI members were recruited and contributed to software with these functionalities is not commercially available telephone interviews lasting 15–40 min. Overall PPI members were either. We aimed to develop such a database and demonstrate its open to using an e-health initiative to self-manage their joint pain; user-friendliness and audit/quality improvement (QI) functionality. Facilitators that encouraged PPI members to use Myjointpain.org Methods: The new database was created using MS Access 2010. included: the interactive nature of the e-health programme; the Fields included indications, immediate side effects, serum creatinine personalized action plan, and participants’ perceived trustworthiness and estimated glomerular filtration rate, pre-dose adjusted calcium, of the content of the website. However, excess information was reported vitamin D and parathyroid hormone, pre- and post-dose pulse and as a barrier of use, as well as finding time to use the website due to busy blood pressure (BP). A function was created to automatically generate lifestyles. The use of email/telephone prompting was thought may help next due date, and another to view a list of patients in order of next due people better engage with online self-management programmes. date. Data were electronically migrated from MS Excel database; Conclusion: PPI members with hip and/or knee OA in the UK report that additional data were entered from case records and Pathology they are receptive and open to considering using the Myjointpain.org database. Database training was provided for department clinicians web based e-learning self-management programme. Such an approach and their views sought via questionnaire. To demonstrate its audit that emphasizes personalized and interactive aspects to facilitate self- functionality, data for adjusted calcium, BP and date of dose were management helps promote engagement with self-management. collated via a query, and processed in MS Excel for descriptive Prompting is helpful in maintaining engagement (e.g. via email) and statistics. provision of too much information may prevent people from engaging Results: Ten senior clinicians attended training. On a scale of 0 (poor) with the programme. Myjointpain.org presents an exciting opportunity to 5 (excellent), questionnaires revealed (mean ratings): user-friendli- for e-health strategies for people with arthritis in the UK. ness (4.6), quality of presentation (4.6), quality of training received (4.5), Disclosure statement: The authors have declared no conflicts of suitability of the programme to its clinical (4.6) and audit purposes (4.9) interest. and clarity of the user guide (4.4). Fifty patients (46 female) received a total of 100 doses. Adjusted calcium was within normal range before every dose. Following one dose, systolic BP dropped >20 mmHg to 142. PROGRESSIVE RESISTANCE TRAINING CLASSES IN 96 mmHg. Following six doses, systolic BP dropped by >20 mmHg, COMBINATION WITH WEEKLY MEDICAL REVIEW but remained >100 mmHg. Systolic BP of 90 mmHg was recorded 1 1 1 1 Shoma Banerjee , Stephen Ritchie , Berna Berntzen , Nisha Munro after one dose from 104 mmHg pre-dose. However, none experienced and Lyn Williamson1 clinical symptoms due to hypotension. Twenty-six patients received at 1Rheumatology, The Great Western Hospital, Swindon, UK least two doses. The median period between doses was 7.3 months (range 5.7–13.6). Repeat denosumab was delayed (>7 months Background: Inflammatory arthritis is associated with numerous ad- between injections) on 30 occasions (60%). verse changes in body composition and physical function that persist Conclusion: Our new database was found to be user-friendly by despite pharmaceutical treatment. Randomized control trial evidence clinicians and capture prospective data for audit and QI functionality. has shown that progressive resistance training (PRT) is safe and effi- Its audit function demonstrated that we are delivering denosumab with cacious in restoring lean mass and function in patients with inflammatory appropriate monitoring. It also demonstrated that repeat doses have arthritis, resulting in the recommendation for the inclusion of PRT in been delayed in 60% beyond the internal target of within a month of treatment strategies for inflammatory arthritis patients. We set up our due date. With the due date function in the new database, we expect own PRT programme for patients with inflammatory arthritis to explore this delay to reduce to within target over the next 24 months when we whether similar results could be achieved in a National Health Service plan to re-audit. (NHS) setting. Disclosure statement: The authors have declared no conflicts of Methods: Patients with inflammatory arthritis are invited to attend a PRT interest. programme. A weekly class is held under the supervision of a senior physiotherapist, with medical input on request. After the six week PRT i106 Wednesday 29 April 2015 POSTER VIEWING II

programme patients were encouraged to continue at home or referred to during pregnancy or breastfeeding. Following significant input from a their local gym. The exercises used within the circuit are: wall slides, sample of the target audience, an information leaflet was produced chest presses, leg extension, rowing, balance board work, tricep which provides guidance on this subject. The majority of patients who extensions, bicep curls, clam, bridging, standing calf raises and step reviewed a final draft were satisfied by its contents, readability and ups. Patients are asked to record their impression of the class on structure. Following positive patient feedback, the leaflet was anonymous comment cards and had the following parameters measured accepted for publication by CMFT and will be made readily available at baseline and at 6 weeks: height, weight, hip and waist circumference, to SLE patients attending clinics at the trust. sit-to-stand time, Hospital Anxiety and Depression Scale, HAQ, Visual Disclosure statement: The authors have declared no conflicts of Analogue Scale Score, Single Leg Stand time,% body fat, grip strength, interest. sleep scale and Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) score. Medical reviews carried out at physiotherapy or 144. DEVELOPMENT OF A PHYSICAL ACTIVITY patient request, provided an opportunity to discuss concerns, perform PROGRAMME FOR PEOPLE WITH RECENTLY DIAGNOSED injections and escalate treatment in those not in remission. RHEUMATOID ARTHRITIS Results: 68 patients have attended the PRT class. 48 persisted to 6 weeks. The physiotherapy team report that patients are more engaged Fiona Cramp1, Janet Withall1, Anne Haase2, Nicola Walsh1, in the context of group exercise. Common themes from patient Anita Young3 and Sarah Hewlett1 feedback include increased confidence in taking part in physical 1Faculty of Health & Applied Sciences, University of the West of exercise, improved sleep and reduced fatigue: ‘I’ve started going to England, 2Centre for Exercise, Nutrition and Health Sciences, the park again after being told that exercise will not harm my joints; I’ve University of Bristol and 3Patient Research Partner, Faculty of Health got the confidence to go and exercise by myself; My grip has really & Applied Sciences, University of the West of England, Bristol, UK improved and I have a lot more energy; I dropped two dress sizes; and I feel stronger which has helped me to return to work.’ Background: People with RA are less physically active (PA) than the Conclusion: We present a model for PRT workable in the NHS since it is general population with lower PA levels associated with work disability, both time efficient and effective. It is an example of coordinated reduced physical function and comorbidities. This suggests an urgent multidisciplinary team care. The classes foster motivation, confidence need to identify programmes that effectively promote sustainable PA to and a belief in exercise as part of effective treatment, which is likely to improve physical function in RA. The purpose of this research was to lead to more significant and sustained results. Our programme offers the seek patient’s views in relation to a range of potential PA programmes. unique benefit of providing weekly access to medical review as required, Methods: Focus groups were carried out with adults with RA with which would not be part of the standard model of care, allowing us to participants purposefully sampled to reflect a range of age and gender. identify those who are not in remission and treat to target. Prior to commencing the research a draft interview guide was Disclosure statement: The authors have declared no conflicts of reviewed by the study Patient Research Partner and a pilot interview interest. conducted. The interview guide was designed to explore PA support needs and experiences since diagnosis as well as motivators and facilitators to support engagement in PA. Each focus group was 143. A NEW EVIDENCE-BASED INFORMATION LEAFLET subsequently provided with information regarding potential PA FOR SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS programmes and invited to comment upon their suitability for people PROVIDING GUIDANCE ABOUT THE USE OF MEDICATIONS with a recent diagnosis of RA. Focus groups were audio-recorded, DURING PREGNANCY AND BREASTFEEDING transcribed and anonymized. Ethics approval for the study was Roya Behrouzi1 and Ian Bruce2 obtained. Written informed consent was obtained from all participants. 1School of Medicine, University of Manchester and 2Rheumatology, Thematic analysis was used to identify the main themes across the Manchester Royal Infirmary, Central Manchester University Hospitals, groups. Emerging themes were verified through discussion and a Manchester, UK coding framework based on these themes developed. Themes and subthemes were subsequently reviewed and the interpretation and Background: SLE occurs most frequently in women of childbearing analysis discussed and agreed. age and can be managed using a variety of anti-inflammatory and Results: Three focus groups were conducted with 19 patients in total antirheumatic drugs. These drugs have varying safety profiles during (15 female, 4 male), with a mean age (S.D.) of 60 (10) years and mean conception, pregnancy and lactation. It is therefore vital that SLE time (S.D.) since diagnosis of 44 (34) months. There was strong support patients have sufficient knowledge about their safety and risks before for a PA programme with four key themes garnered from the focus planning for pregnancy or breastfeeding. The aim of this study was to groups: recruitment and adherence included programme endorsement develop an evidence-based information leaflet for female SLE patients from peers and PA endorsement from health professionals; the need of childbearing age which would provide guidance about taking for support to overcome barriers to PA, such as pain and fatigue; and medications during pregnancy and breastfeeding. prompts such as text messages to improve adherence. Programme Methods: From February to April 2014, 19 female SLE patients (18–50 scheduling included timing with most suggesting 6–12 months years), of which 10 were pregnant, were interviewed at the Lupus in following diagnosis, once a stable drug regime was established; Pregnancy (LiPs) and general SLE clinics at the Central Manchester afternoon sessions were preferred; views on frequency of sessions Foundation Trust (CMFT). Interviews were semi-structured, based and duration of the programme were disparate. Programme content around a questionnaire and carried out during both the planning and included support for education on relaxation and coping strategies, developmental stages of the leaflet. Patients’ views were obtained medication, flare, fatigue and pain; supervised exercise sessions; regarding the perceived demand for the leaflet as well as its contents, home exercise training; and expert physiotherapy input. Goal setting readability and structure. received mixed opinions with emphasis on the need to be patient-led. Results: 18 (95%) patients believed there was not enough lay Programme delivery suggested group sessions were preferred by information available about taking SLE medications during pregnancy most, but not all; individual sessions in addition to the group were and breastfeeding. When asked to rate their own knowledge about the positively received; telephone support polarized opinion; but an safety and risks of taking SLE medications before conception, during accessible location was an agreed priority. pregnancy or during breastfeeding (0, very poor; 10, very good), Conclusion: Participants supported development of a PA programme patients received mean scores of 4.2, 3.5 and 2.2, respectively. delivered at an accessible location, by physiotherapists within 6–12 19 (100%) patients believed that they would find an information leaflet months of diagnosis. Mixed views relating to delivery suggests a on this subject useful. Following a literature review of the safety of SLE flexible approach may need to be developed. drugs during reproduction, an A5, six-page pilot leaflet was produced. Disclosure statement: The authors have declared no conflicts of Information was divided into two sections discussing pregnancy and interest. breastfeeding separately. A traffic light rating system was used in both to stratify medications based on relative risk into unsafe, use with 145. USING QUALITATIVE RESEARCH METHODS TO caution or safe, accompanied by justifications. This concept was DEVELOP A PACKAGE OF CARE FOR PATIENTS LIVING WITH approved by 19 (100%) patients. The Gunning fog index for the text OSTEOARTHRITIS (excluding drug names) was 8.8, confirming readability by a wider audience. Of 14 patients who reviewed a final draft, 14 (100%) were Sarah Drew1 and Nigel Arden1 satisfied by its readability and structure, 13 (93%) by its contents and 1Nuffield Department of Orthopaedics, Rheumatology and depth of information and 13 (93%) believed it was superior to lay Musculoskeletal Sciences, University of Oxford, Oxford, UK information already available. Conclusion: This study suggests female SLE patients of childbearing Background: OA is a common condition that can have a profound age do not have sufficient knowledge or enough access to lay effect on patients’ physical and emotional wellbeing. Despite guidance information about the safety and risks of taking SLE medications on how best to manage OA, evidence suggests that care is often POSTER VIEWING II Wednesday 29 April 2015 i107

inadequate. This study aims to use qualitative research methods to The facilitation themes included: meeting others and feeling less develop a package of care to improve patient experiences of isolated; making the invisible visible, an increased confidence in accessing services. managing the invisibility of the condition through feeling increasingly Methods: This study was conducted in four phases. In phase 1, a group validated, in turn helping with putting into practice tools around discussion with five healthcare professionals involved in delivering care communication and pacing; the role of the patient partner was for OA patients was used to develop a package of care. This was based identified as helping to facilitate discussion; participants talked about on the priorities for implementation identified in OA National Institute for how the course had enabled them to begin to accept their arthritis Clinical Excellence guidelines and clinical experiences. In phase 2, a enabling change in the path to acceptance; and underpinning this was narrative synthesis of qualitative research was conducted to increase our the opportunity for emotional processing. The second theme relating understanding of patient experiences of accessing services and to to barriers included not enough time to process more difficult identify gaps in care. This involved a comprehensive review of studies emotions; slipping back and struggles to maintain behaviour changes using CINAHL, MEDLINE, PubMed and the Cochrane Library published over time; fighting it and stigma, including struggles to accept and feel between January 2007 and September 2014. Articles were manually able to make changes without feeling judged, often identifying screened to identify studies relevant for inclusion. Studies were imported additional stressors, such as financial loss. into NVivo qualitative analysis software and a thematic analysis Conclusion: The focus groups produced a rich narrative surrounding conducted to identify themes and subthemes. In phase 3, findings process factors associated with the Living Well with Arthritis course. from phase 2 were used to modify the package of care developed. In Key facilitators to change were being with others who understood and phase 4, two focus groups with eight patients diagnosed with OA were validated their experience of living with inflammatory arthritis, and then conducted to receive their views on the package of care. Focus recognizing the importance of confidence in adjusting to inflammatory groups were audio-recorded, transcribed and anonymized. A thematic arthritis and becoming effective self-managers. Negative emotionality analysis was conducted (as above). and a need for more time were identified as significant barriers to Results: In phase 1, key areas for implementation were identified by change. the expert panel and strategies suggested for addressing these. In Disclosure statement: The authors have declared no conflicts of phase 2, patient experiences of accessing care were generally interest. negative. Areas of improvement identified were the improved attitudes of healthcare professionals; more efficient diagnoses; longer consulta- tions; specialist input in primary care; access to a range of services 147. PATIENT PERSPECTIVES ON THE OPTION GRID FOR such as physiotherapy and joint replacement surgery if necessary; OSTEOARTHRITIS OF THE KNEE access to pharmacological treatments to manage pain; proactive and Jill Firth1, Katharine L. Kinsey1, Fiona Wood2, Katy Marrin2, regular follow up; appointments with the same specialists each visit; Alan Nye1 and Glyn Elwyn3 improved communication and coordination between services; and 1Rheumatology, Pennine Musculoskeletal Partnership, Oldham, information and education, especially at the point of diagnosis. Phase 2Institute of Primary Care and Public Health, Cardiff University, 3: gaps in care were used to refine the package of care. Phase 4: Cardiff, UK and 3Dartmouth Centre for Healthcare Delivery Science, participants in focus group one were enthusiastic about the package Dartmouth Centre, Dartmouth, MA, USA of care developed, while those in focus group two were less so, prioritizing access to joint replacement surgery. There was a lack of Background: Option Grids are frugal tools that make patients aware consensus on the most effective strategies to deliver it, suggesting of the existence of choice by displaying competing options side by that it should be sufficiently flexible and tailored to meet the needs of side, organized by the concerns that frequently occur to increase the individual patients. potential for patient activation. A stepped wedge design clinical trial Conclusion: Findings from this study will be used by clinicians to was conducted in which the Option Grid for OA of the knee was modify and refine the package of care developed. It is hoped that this allocated sequentially to participating physiotherapists to use within a will enable healthcare professionals to design and deliver a service to routine consultation after having consulted with six patients using better meet the needs of patients. usual care procedures (control). Nested in this clinical trial, we Disclosure statement: N.A. has provided consultancy services to undertook qualitative research to evaluate the acceptability and Merck, Merck Sharp and Dohme, Roche, Novartis, Smith and Nephew, impact on engagement in shared decision-making of the Option Q-MED, Nicox, Flexion, Servier, GSK, Bioventus, Bioberica, Schering- Grids from a patient perspective, the results of which we report here. Plough, Pfizer and Rottapharm; has served on speakers’ bureaus on Methods: Consultations with 36 patient participants (6 physiothera- behalf of ESCEO; and has received research funding from OATcS. The pists consulting with 6 patients each) pre-intervention and 36 post other author has declared no conflicts of interest. intervention were observed and audio-recorded. Post hoc short semi- structured interviews were undertaken with all 72 patient participants 146. A QUALITATIVE EVALUATION OF THE LIVING WELL and the Rapid Estimate of Adult Literacy in Medicine (REALM-R) WITH ARTHRITIS COURSE measure of health literacy recorded. Observation notes and interview data were transcribed and coded using software to explore views on Kate Druett1, Marianne Morris2, Nicola Minaur1 and the consultation, perceptions of involvement in decision-making and Christine Silverthorne1 the use of the Option Grid. Using a coding framework, one member of 1Rheumatology, North Bristol NHS Trust and 2Faculty of Health and the research team coded all interview data (K.M.), and another dual- Life Sciences, University of the West of England, Bristol, UK coded a 30% sample of interviews (K.K.). A thematic analysis was undertaken to look for patterns in the data to inform future use of the Background: Recent research has identified the benefits of self- Option Grid. Transcripts of the audio-recordings were examined for management programmes underpinned by cognitive behavioural data to support or challenge the qualitative analysis. approaches, including reduced fatigue, improved mood and improved Results: Interview and observation data suggest that the implementa- quality of life. The Living Well with Arthritis course draws on elements of tion of the Option Grid facilitated a more detailed discussion around the programme developed by the North Bristol Trust Co-Creating Health the risks and benefits of a wider range of treatment options for knee team. The key aim is to support adults with inflammatory arthritis to OA. Participants indicated that the Option Grid was clear and aided become more confident in managing their condition, to enable the their understanding of a structured progression though a range of person to live well socially, physically and emotionally. The course was options and possibly facilitated their involvement in the decision- co-delivered by a trained patient partner and clinical psychologist to making process. Consultation data appeared to support this and small groups over seven weekly 3-h sessions. Topics included coping REALM-R scores did not appear to influence patient perspectives with fatigue, pain and stress, and communication skills. Referrals onto around understanding of risks and benefits. There were variations in the course were via members of the rheumatology team. A qualitative the way that the Option Grid was implemented in relation to how the evaluation was designed in order to review the experiences of course options, benefits and risks were presented to the patient. While participants and to evaluate the course content and its impact. clinicians tailored information about treatment options to participants Methods: Focus groups were employed because they facilitate in both groups, in consultations without the Option Grid the clinician participant interaction and reduce research influence. All previous was reported to have selected options for discussion and did not refer participants (20 patients) were invited to attend one of three focus to other options, such as total knee replacement, which may have groups, each lasting 90 min. 14 women participated, average duration been deemed clinically inappropriate. of inflammatory arthritis of 8 years. An interview guide was devised by Conclusion: The Option Grid for OA knee was well received by the research team based on previous evaluations and with input from a participants and appeared to facilitate greater understanding of patient partner. treatment options and possibly greater engagement in shared Results: A number of themes were identified, falling into two broad decision-making. categories: processes within the course that helped facilitate and Disclosure statement: J.F., K.L.K, F.W., K.M., A.N. and G.E. have those which acted as barriers to adjusting to inflammatory arthritis. received research funding from the Bupa Foundation. i108 Wednesday 29 April 2015 POSTER VIEWING II

148. DEVELOPMENT OF A FIBROMYALGIA EXPERIENCE translation of the recordings an Arabic-speaking physiotherapist QUESTIONNAIRE: FOCUS GROUP AND PILOT reviewed the Arabic text and generated codes independently. QUESTIONNAIRE RESULTS Thematic analysis was undertaken with the help of qualitative 1 2 2 computer software. The initial codes were independently validated Ashley Hawarden , Angela Campbell , Fiona Gaskin-Colligan , by an external qualitative researcher. Findings were reviewed with a Peta Heslop3, Sandra Robinson3 and David Walker4 1 senior physiotherapist and a patient. Medicine, University Hospital of North Midlands, Stoke-on-Trent, Results: Eighteen participants attended all three focus groups. These 2Fibromyalgia Group, NewcastleFibro, 3Research and Development, 4 comprised 14 females and 4 males, aged 25–74 [47.44 (S.D.11.58)] Northumbria Healthcare NHS Foundation Trust and Rheumatology, years. Nine were in full-time employment, three were retired, four were Newcastle Upon Tyne Hospitals NHS Foundation Trust, Tyne and housewives, one a student and one unemployed. Participants lived with Wear, UK LBP from 3 months to 20 years. Mean (S.D.) pain score was 5.28 (1.97). Participants preferred to be within same-sex groups. Only one female Background: People with FM often express dissatisfaction with the participant did not contribute to the discussion. Findings are presented way they are treated within the National Health Service (NHS). We within the framework of four main themes that emerged from the were interested to develop a questionnaire exploring these attitudes qualitative data: living with long-term LBP (e.g. the nature of pain, with a successful local self-help group. relationships with others, loss of independence); the adoption of self- Methods: Initially an exploratory focus group consisting of a management strategies to cope with LBP (e.g. religious coping, following convenience sample of six interested members was held. The topic advice); experiences with healthcare professionals (e.g. perceptions of guide, developed with reference to the existing literature, prompted healthcare professionals, physiotherapy and medical experiences); and the group to discuss a variety of aspects of their experience. This re-engaging with the healthcare system to pursue further treatment included delays in diagnosis, symptomology, treatment, attitudes of options (e.g. seeking information, exploring new treatment options). health professionals and both the sources and usefulness of Conclusion: Patients from Bahrain live through similar experiences information used to aid understanding of the condition. and have comparable expectations of the healthcare system to Results: Participants timed the delay from first presentation to patients from studies conducted in Western cultures. However, diagnosis in years, with one at 32 years. Reasons ranged from the religious coping (e.g. religious expressions, adopting comfortable general practitioner (GP) not believing in it or the GP not understanding prayer positions) are not common in Western populations. Additionally, it to the patient not presenting the symptoms in the right way. The understanding culture-specific social relationships could inform participants were passionate about health professional attitudes. All of clinicians how to advise patients with pacing activities of daily living, them described at least one negative encounter. GPs were thought to communicate their pain experience and delegate home or work be variable in their belief and attitude towards FMS with younger ones responsibilities. Addressing individuals’ culture-specific psychological being more sympathetic. The participants tended to use FMS society and social factors in clinical settings with Arabic patients might information rather than Arthritis Research UK (ARUK) which they saw improve patients’ involvement in treatment in Bahrain and the Middle as being for arthritis rather than myalgia sufferers. They wished to find East, and in migrant Arab and Muslim populations in the UK. more UK sources on the internet rather than US. Thematic analysis of Acknowledgement: This work is part of a research project (D.M.) for a the focus group data was then used to inform an exploratory Ph.D. at King’s College London (London, UK) funded by the Crown questionnaire. The pilot questionnaire was administered by the Prince International Scholarship Programme (Kingdom of Bahrain). support group lead both electronically and in paper form. It sought Disclosure statement: The other authors have declared no conflicts to collect both quantitative and qualitative data. 20 members of the of interest. support group piloted the questionnaire. 17 were female with median age in the 50s (range 20s to 70s). Six were going out to work, four were retired, nine were on sickness benefits and one was a homemaker. 14 150. DEEP PROSTHETIC JOINT INFECTION: IMPACT ON were diagnosed by rheumatologists, 3 by a GP and 2 by pain PATIENTS AND PREFERENCES FOR TREATMENT consultants; 1 was not formally diagnosed. The delay in diagnosis Andrew Moore1 and Rachael Gooberman-Hill1 averaged 7.8 years (range 1 month to 35 years). Interactions with 1School of Clinical Sciences, University of Bristol, Bristol, UK health professionals were explored with a series of nine questions. Six participants scored very negatively, three moderately negative, five Background: Around 70 000 people undergo hip replacement neutral, three moderately positive and three very positive. Fibromyalgia annually in the UK, and about 1% of patients develop deep infection Association information was most used, followed by information at their artificial hip joint. Currently there are two treatment options. provided by the group, then by professionals and ARUK. The 1-stage process involves complete removal of the artificial joint, Conclusion: FMS patients have many problems in their interaction thorough cleaning of the area to remove infected material, and with health professionals and report huge delays from the onset of immediate insertion of a new joint. The 2-stage process involves symptoms to diagnosis. The questionnaire could be usefully shortened removal of the artificial joint and delaying its replacement for 3–6 to the most informative areas and administered to a wider population. months. Although a temporary device or spacer may be used, patients Disclosure statement: The authors have declared no conflicts of have no permanent joint until a replacement is inserted in a second interest. operation. Both methods are used in conjunction with antibiotics. The impact of deep joint infection on patients is not well understood. 149. LONG-TERM LOWER BACK PAIN IN ARAB PATIENTS We aimed to characterize the experience of deep joint infection and AN EXPLORATION OF EXPERIENCES, BELIEFS AND its treatment on wellbeing, satisfaction with healthcare, and to EXPECTATIONS IN BAHRAIN identify treatment preferences. Findings will inform the design of a fully powered randomized trial to compare 1-stage with 2-stage Dana Maki1, Duncan J. Critchley1, Paul J. Watson2 and treatment. Heidi Lempp3 Methods: In a qualitative interview study we conducted face-to-face 1Department of Physiotherapy, King’s College London, London, interviews with 15 patients treated for deep hip joint infection in the 12 2Department of Health Sciences, University of Leicester, Leicester months prior to recruitment. Patients were identified through 6 UK and 3Department of Academic Rheumatology, King’s College orthopaedic treatment centres. Interviews explored experience of London, London, UK infection, treatment and recovery. With informed consent, interviews were audio-recorded, transcribed and imported into NVivo data Background: Long-term lower back pain (LBP) disability is associated management software. Data were analysed using constant compar- with psychological (e.g. coping strategies, beliefs) and social (e.g. ison. Transcripts were coded in vivo, 4 transcripts were independently relationships, patient’s environment) factors. Knowledge of these double-coded and a code list derived, applied and refined as factors can help inform patient management. Culture is known to appropriate. Coded data were grouped, using inductive methods, affect the pain experience through language, beliefs and attitudes but into categories. Data from patients in the 1-and 2-stage groups were studies to date have examined social and psychological factors largely analysed separately allowing for any differences in experience in Western settings. The purpose of this study is to explore LBP beliefs between the groups to become apparent. Data sets were then and experiences of Arabic patients to inform clinicians working within compared and contrasted. an Arabic cultural context. Results: Patients with deep joint infection reported pain, reductions or Methods: A qualitative approach was adopted and three focus groups loss in mobility, loss of valued activities, changes to their home of 4 to 8 patients were conducted, stratified by age, duration of LBP environments or moving into care, negative impact on personal and gender from three different hospital sites in Bahrain. Recordings of relationships, and economic burden.. Patients described physical the focus groups were transcribed verbatim into Arabic (original and psychological trauma associated with surgical and antibiotic language) and then translated into English. To corroborate the treatment. When describing preferences for 1-stage revision, patients POSTER VIEWING II Wednesday 29 April 2015 i109

valued these issues above concerns about difference in efficacy of physical activity (PA) have been shown to improve patient-reported eradication of infection. Patients identified a clear need for additional fatigue in other long-term conditions. The aim of this study was to support after surgery, particularly for those undergoing 2-stage explore rheumatology allied health professionals’ (AHPs) views revision. Although they saw a future trial to compare 1-stage with regarding the acceptability of a PA intervention for managing RA 2-stage revision as important, patients had strong preferences for fatigue, to identify key components for inclusion and to discuss treatment and found randomization a difficult concept. implementation in clinical practice. Conclusion: The impact of deep joint infection has profound impact Methods: A purposive sample of rheumatology AHPs took part in one on physical, emotional, social and economic aspects of patients’ lives. of two focus groups. Transcripts were analysed using thematic There is a need to provide additional support for patients undergoing analysis with a subset analysed independently. revision treatment. Findings suggest that patients found it hard to Results: Seven physiotherapists and two occupational therapists took accept the idea of randomization to treatment, and that design of a part; age range 37–50 years; time working in rheumatology 5–15 years. future trial should consider the issue of potentially strong patient Five themes were identified. Current practice: AHPs felt that healthcare preferences. professionals could do more to support patients experiencing fatigue. Disclosure statement: The authors have declared no conflicts of Fatigue management was not prioritized, although it was sometimes interest. discussed in general RA education programmes. Current physiother- apy practice, including PA advice, focused on specific joint or mobility problems and physical function. Attitudes and beliefs: AHPs believed 151. NURSES’ VIEWS ON METHOTREXATE EDUCATION: that patients might not access physiotherapy to manage fatigue if they COMMUNICATION AND CONSULTATION thought PA would make fatigue worse. Some participants recognized Sandra Robinson1, Sarah Ryan2, Andy Hassell3, Peta Heslop1, the influence of psychosocial and lifestyle factors on fatigue, whereas Stacey Duffy1 and David Walker4 others believed that disease processes and other medical issues 1Research and Development, Northumbria Healthcare NHS caused fatigue and required medical management. Some questioned Foundation Trust, Tyne and Wear, 2Rheumatology, Haywood whether there was a need for a specific PA programme for managing Hospital, Stoke-on-Trent, 3Rheumatology, Keele University, Keele fatigue and thought fatigue management could be incorporated into a and 4Rheumatology, Newcastle Hospitals NHS Foundation Trust, general PA programme. Ideas for a new intervention: implementing an Newcastle Upon Tyne, UK intervention was perceived as feasible, particularly a group pro- gramme that would likely be more cost-effective than individual Background: The education of patients is a central part of the nursing sessions. Groups also offer peer support for patients, although there role in the UK. Nowhere is it more important than in relation to drugs were concerns that individualizing group PA would be challenging. such as MTX, where the effect is delayed and side effects are Lack of staffing and resources were highlighted as additional anticipated. Nurses had expressed variable confidence in educating challenges for implementation and delivery. Participants supported patients starting MTX. We were interested to explore these issues in the inclusion of goal setting and problem solving, and addressing semi-structured interviews with nurses engaged in this role. motivation and barriers to PA. A graded approach to PA incorporating Methods: Six nurses who perform this role in two large units were aerobic capacity and strength training was felt to be important. interviewed. They were all monitoring rather than specialist nurses and Potential outcome: AHPs believed that PA could make a positive worked in two different systems. In the first system patients were difference to fatigue in addition to having other benefits such as educated on the spot and in the second patients were given increased social participation, improved psychosocial wellbeing, appointments to return to a dedicated clinic. The interview schedule better sleep and improved sense of control over RA. Long-term covered: training; teaching session content; written information used; adherence: The importance of implementing strategies to facilitate time and confidence. The interviews were transcribed and analysed ongoing PA was highlighted. Therapy input must be supplemented by using framework analysis a standard qualitative methodology. PA practice at home. Improved links with community services would Results: All nurses used a written leaflet or checklist to dictate the be needed to ensure long-term continuation of PA. content of the education. All covered the important side effects, how to Conclusion: AHPs believed that current fatigue management in RA take it and how the monitoring and prescription system worked. The could be improved. They supported the use of PA to manage fatigue checklist did, however, have the effect of making a one way dialogue but concerns regarding implementation and delivery must be described as their speech (or spiel) and nurses described being considered during intervention development. interrupted or thrown off track by patient questions. None of the Disclosure statement: The authors have declared no conflicts of participants were able to describe a recent teaching session without interest. reference to the leaflet they used. Checking of the patient’s knowledge and understanding prior to the education did not occur. It was 153. DEVELOPMENT OF A PHYSICAL ACTIVITY assumed that patients who were already on DMARDs did not require INTERVENTION FOR RHEUMATOID ARTHRITIS FATIGUE: as much education: they just need an overview – like the side effects PATIENTS’ VIEWS and you don’t go into it as much. Similarly a checking for under- standing during the delivery of the education was also missing. Some Victoria E. Salmon1, Sarah Hewlett1, Nicola Walsh1, John R. Kirwan2, nurses felt they were under time pressure bombarding the patient with Marie Urban2, Maria Morris2 and Fiona Cramp1 information. This was found in both systems, even with specific 1Faculty of Health and Applied Sciences, University of the West of appointments. Questions about the disease, rather than the drug, were England and 2Academic Rheumatology, University of Bristol, Bristol, usually side stepped with an offer to arrange an appointment with a UK specialist nurse. Training was generally confined to observing the process then they got on with it. Background: Fatigue is often reported as a problem by people with Conclusion: The content of these educational encounters relied RA. Programmes based upon physical activity (PA) have been shown heavily on the written materials. This material also seemed to constrain to improve patient-reported fatigue in other long-term conditions, but the encounter with an overwhelming need to get through it. Delivery of RA patients’ views regarding the use of PA to manage fatigue are information was constant and nurses felt that they were bombarding currently unknown. This study explored patients’ opinions about the patients with information leaving them feeling dazed and over- use of PA for fatigue management, including their support needs and whelmed. The nurses quickly established good rapports with their delivery preferences. patients, but their consultation skills may require further development. Methods: A purposive sample of adults with RA who had experienced Disclosure statement: The authors have declared no conflicts of self-reported fatigue since diagnosis participated in one of two focus interest. groups. Discussions were audio-recorded and transcripts analysed using thematic analysis. 152. DEVELOPMENT OF A PHYSICAL ACTIVITY Results: The study included 12 patients (6 female) aged 43–66 years INTERVENTION FOR RHEUMATOID ARTHRITIS FATIGUE: (mean 56.8) with a disease duration of 0.25–25 years (mean 8.2) took ALLIED HEALTH PROFESSIONALS’ VIEWS part. Three key themes were identified: Internal factors: Various self- management and coping skills for fatigue were described but these Victoria E. Salmon1, Sarah Hewlett1, Nicola Walsh1, John R. Kirwan2, were not applied consistently. Support for fatigue management was Marie Urban2, Maria Morris2 and Fiona Cramp1 mainly sought from family members despite a limited understanding of 1Faculty of Health and Applied Sciences, University of the West of the experience. Peer support from other RA patients was considered England and 2Academic Rheumatology, University of Bristol, Bristol, invaluable by both men and women; therefore, patients supported a UK group intervention. Motivation for PA: Participants reported that getting outside, being creative and enjoying a sense of achievement Background: There are currently few programmes available to help helped motivate them to be physically active. Internal factors such as RA patients manage symptoms of fatigue. Programmes based upon determination and a positive attitude were also considered important. i110 Wednesday 29 April 2015 POSTER VIEWING II

However, this positivity was often overridden by experiences of FP7-HEALTH-F2-2012-305549 (EuroTEAM) and funding from repeated failure with PA. External factors such as the physical the Swedish Foundation for Humanities and Social Sciences (mind- environment affected motivation and participation in PA. Enhancing the-risk). opportunities to engage in PA was suggested to facilitate motivation. Disclosure statement: The authors have declared no conflicts of External factors: Professional support for fatigue management was interest. rarely sought by patients. Those who had received advice found it to be limited. PA advice was generally aimed at improving physical 155. ENHANCED ROLE OF HEALTH CARE ASSISTANTS IN function rather than managing fatigue. Employment and other caring PATIENT EVALUATION THROUGH DAS28 ASSESSMENT roles and responsibilities made it difficult to prioritize PA, and fatigue management was challenging as patients felt they had no choice but Emma Toms1, Lucy Knight1, Philip P. Stapleton1 and to soldier on in order to meet external demands. Attending a fatigue Sandeep Dahiya1 management programme would be difficult for those who work, 1Rheumatology, Peterborough and Stamford Hospitals NHS particularly if delivered during working hours. Foundation Trust, Peterborough, UK Conclusion: Patients supported the development of a PA intervention to improve RA fatigue. Patient perspectives regarding barriers and Background: DAS for 28 joints (DAS28) is a validated and well- motivators for PA and concerns regarding implementation and delivery established tool for the assessment of disease activity in RA patients. must be considered to support uptake and engagement with PA. This is a useful tool for baseline assessment and response to These findings will inform intervention development. treatment. In most rheumatology centres clinicians or other trained Disclosure statement: The authors have declared no conflicts of members of the multidisciplinary team (MDT) such as nurse practi- interest. tioners complete the DAS28 assessment. We investigated if a non- specialist member of the team such as a Health Care Assistant (HCA) 154. PERCEPTIONS OF TESTING TO PREDICT FUTURE could gain proficiency over a short time period to carry out reliable DEVELOPMENT OF RHEUMATOID ARTHRITIS AMONG THE DAS28 assessments. FIRST-DEGREE RELATIVES OF PEOPLE WITH RHEUMATOID Methods: A HCA Band-2 was given an informal introduction to ARTHRITIS: A QUALITATIVE EXPLORATION DAS28 assessment and initially assisted the rheumatology consultant and nurse practitioner in completing these assessments Rebecca J. Stack1, Marie Falahee1, Michaela Stoffer2, for a few weeks and then completing DAS28 assessments Tanja Stamm2, Gwenda Simons1, Christopher Buckley1, under supervision for 2 weeks. The consultant and HCA separately Kanta Kumar3, Mats Hansson4 and Karim Raza1 assessed the next 10 patients with RA for comparability of these 1Centre for Translational Inflammation Research, University of scores. Birmingham, Birmingham, UK, 2Division of Rheumatology, Medical Results: These data show that there was agreement between University of Vienna, Vienna, Austria, 3School of Nursing, University assessors in reporting the number of tender joints in 7/10 patients of Manchester, Manchester, UK and 4Centre for Research Ethics and and in 8/10 patients with swollen joints (Table 1). Overall, there were Bioethics, Uppsala University, Uppsala, Sweden identical DAS28 scores in 6/10 patients. Interestingly, one patient reported a lower visual analogue score (VAS) when assessed by the Background: Early treatment of RA improves clinical outcomes. There consultant (15) compared with the HCA (20), which resulted in a is increasing recognition of the need to identify people at risk of RA to difference in DAS28 scores although clinical assessment for the monitor the emergence of early symptoms, offer lifestyle advice to number of tender and swollen joints was identical between assessors. reduce the impact of risk factors (such as smoking) and potentially Where discrepancies arose it was noted that the HCA recorded a offer preventive treatment. The family members of people with RA are higher number of tender joints in two patients more than the consultant at an increased risk of developing RA and are likely candidates for and in one patient more and one less patient when assessing swollen predictive testing. However, we do not know how the relatives of joints. people with RA feel about tests to predict their risk of developing RA in Conclusion: This small pilot study shows that non-specialist team the future. members can be trained over a few weeks to complete DAS28 Methods: Twenty-four first degree relatives of patients with RA (8 assessments with comparable and reliable scores and this skill can siblings and 16 adult offspring aged between 18 and 67 years) took enhance the running of rheumatology clinics where HCAs normally part in semi-structured interviews. The interviews explored their carry out other important measurements such as height, weight, blood perceptions on the risk of developing RA and the use of tests to pressure, urine dipstick, Bath AS Disease Activity (BASDAI) and HAQ predict their future risk of developing RA. Interviews were audio- assessments. We feel that HCA assessment of DAS28 scores will not recorded, transcribed verbatim and analysed using thematic analysis. only improve efficiency of busy rheumatology clinics but in addition will Results: First-degree relatives were aware of their susceptibility to offer HCAs opportunities to further advance their knowledge base and developing RA, but were unsure of the extent of their risk. When skills with greater opportunities for career advancement. We plan to considering their future risk, first-degree relatives were anxious and extend this further to a total of 50 patients and if the results remain concerned about the potential impact RA would have on their lives; comparable we would extend the role of HCAs in DAS28 measurement this worry was often heightened by their observations of the difficulties along with other members of the MDT. their relative with RA faced. Some were concerned that knowing their Disclosure statement: The authors have declared no conflicts of risk would increase their anxiety and would have a large impact of the interest. decisions they made about their future. Many felt that they were lacking important information about their susceptibility to RA and were concerned about the levels of uncertainty associated with predictive 155 TABLE 1. DAS28 score comparability between consultant and HCA assessors testing. Some were opposed to testing and felt predictive information would have a negative impact on their lives. Those in favour of knowing Patient Consultant HCA VAS their future risk felt that they would need additional support to understand the risk information, make decisions about their future and SJ TJ DAS28 SJ TJ DAS28 Consultant HCA cope with the emotional impact of this information. 1 1 2 1.63 2 3 1.92 5 5 Conclusion: Identifying those at risk can have a number of benefits in 2 0 0 1.61 0 0 1.89 15 20 reducing disease burden. However, the psychological impact of risk 3 5 0 3.28 2 8 4.01 30 30 4 0 1 1.19 0 1 1.19 10 10 information on those identified and tested must be considered. Not all 5 0 1 2.82 0 0 2.26 5 5 relatives wanted risk information, and those that did recommended 6 0 0 1.41 0 0 1.41 20 20 that additional support should be offered to help them cope with its 7 0 0 1.94 0 0 1.94 10 10 impact. Developing strategies which communicate risk information 8 0 0 1.50 0 0 1.50 10 10 effectively while reducing the emotional burden associated with this 9 0 0 0.51 0 0 0.51 2 2 information is essential. 10 0 0 1.20 0 0 1.20 5 5 Funding statement: The research leading to these data was funded DAS28: DAS for 28 joints; SJ: swollen joints; TJ: tender joints; VAS: visual within the FP7 HEALTH programme under the grant agreement analogue score. POSTER VIEWING II Wednesday 29 April 2015 i111

open-ended question: ‘If you have any additional comments or thoughts you would like to make please write them down below’. BHPR RESEARCH: QUANTITATIVE Data were analysed using quantitative correlational tests and qualitative exploratory case studies analysis. Results: There were 30 participants (26 female), with a median age of 51 years and a mean disease duration of 19.5 years (S.D. 12.5; Table 1). 156. PRELIMINARY VALIDATION OF AN ILLNESS A negative correlation was found between adjustment and neuroticism PERCEPTION QUESTIONNAIRE FOR HEALTHCARE (r ¼0.636, P ¼ 0.01), indicating patients high in neuroticism had PROFESSIONALS poorer adjustment. Qualitative comments added depth: I have adjusted to my condition more in a physical sense than a mental Seher Arat1, Anke Van den Zegel2, Philip Moons2,3, sense and feel it takes a long time to come to terms with (high Joris Vandenberghe4,5 and Rene´ Westhovens1,6 neuroticism, low adjustment). Negative correlations were also found 1Department of Development and Regeneration, Skeletal Biology between adjustment and both avoidance and resignation coping, and Engineering Research Centre, KU Leuven, 2Department of indicating patients with these emotion-focused coping styles had Public Health and Primary Care, KU Leuven, Leuven, Belgium, 3The poorer adjustment (r ¼0.506, P ¼ 0.01; r ¼0.428, P ¼ 0.05, respec- Heart Centre, Copenhagen University Hospital, Copenhagen, tively): ‘It’s been a shock and I thought I would have adjusted by now Denmark, 4Liaison Psychiatry, University Hospitals Leuven, to having a chronic condition, but it just hits me sideways sometimes’ 5Department of Neurosciences, Research group Psychiatry and (high avoidance, low adjustment). A correlation between resignation 6Rheumatology, University Hospitals Leuven, Leuven, Belgium coping and neuroticism was found (r ¼ 0.500, P ¼ 0.01). However, no relationship was found between avoidance coping and neuroticism. Background: Conflicting illness perceptions between patients with Both neuroticism and avoidance coping were negatively correlated rheumatic conditions and healthcare professionals in rheumatology with patients’ disease duration (r ¼0.531, P ¼ 0.01 and r ¼0.476, might cause problems in communication and decision-making. To P ¼ 0.05, respectively), indicating RA patients with <20 years disease date, there is no mutual measurement tool available to compare the duration have higher neuroticism and use more avoidant coping. illness perceptions between these two groups. The Revised Illness Furthermore, adjustment was found to be correlated with patients’ Perception Questionnaire (IPQ-R) is a widely used instrument in many disease duration (r ¼ 0.573, P ¼ 0.01) indicating that patients with patient populations (RA, SLE, scleroderma, systemic vasculitis and greater disease duration show better adjustment. OA) with good psychometric properties. For assessing the perception Conclusion: Neuroticism and emotion-focused coping negatively of healthcare professionals, regarding the illness of a patient, the IPQ- influence RA patients’ adjustment and the neuroticism personality R needs to be adapted and evaluated for use. Therefore, the aim of trait accounts for more resignation coping in RA patients. Disease this study was to explore the face and content validity of the IPQ-R for duration is an important factor influencing RA patients’ adjustment. healthcare professionals. Clinicians should be aware that personality and coping style can Methods: Four researchers discussed on the items, rephrasing of the influence patients’ ability to adjust and adapt to their RA. items and adapting the original IPQ-R to a healthcare professionals’ Understanding this difference in adjustment is necessary to inform version (IPQ-R HP). The illness identity and causality dimensions of the the design of self-management interventions and to tailor treatment IPQ-R were omitted. The other seven dimensions (i.e. 38 items) of the approaches to the individual. original version were kept. Twenty medical experts out of eight medical Disclosure statement: The authors have declared no conflicts of disciplines from three general hospitals in Flanders were approached to interest. participate in the study. Face validity of the IPQ-R HP was evaluated by asking four structured questions for each of the seven dimensions of the 157 TABLE 1. Correlations between personality traits, coping, adjustment and years questionnaire. Content validity was evaluated by instructing the experts of diagnosis to rate the 38 items of the IPQ-R HP on a 4-point Likert scale on their Personality trait Neuroticism Avoidance Resignation Adjustment relevancy. The results were quantified using the content validity index coping coping (CVI) on item level (I-CVI) and scale level (S-CVI) and a modified kappa Adjustment index (k*). The k* is the I-CVI adjusted for chance agreement. Pearson correlation 0.636** 0.506** 0.428* — Results: Seventeen medical experts completed the questions concern- (two-tailed) 0.000 0.005 0.018 — ing the face validity of the IPQ-R HP. Their comments were related to the n 30 29 30 — composition of the original IPQ-R. A total of 16 experts evaluated Neuroticism content validity. Twenty-five of 38 items demonstrated excellent content Pearson correlation — — 0.500** — validity (I-CVI 0.78 and k* >0.74) and seven items showed good two-tailed) — — 0.005 — content validity (I-CVI <0.78 and 0.60 k* 0.74). Four items had a n — — 30 — Years since diagnosis sufficient k* (0.40 k* 0.59) and two items had a very low k*(k* < 0.40). Pearson correlation 0.531** 0.476* — 0.572** These two items were: the illness of my patient strongly affects the way (two-tailed) 0.004 0.012 — 0.001 others see him/her, and the illness of my patient will pass quickly. The n 28 27 — 28 average CVI of the seven dimensions ranged from 0.72 to 0.91. *Correlation is significant at the 0.05 level (2-tailed), **correlation is significant at Conclusion: The IPQ-R HP shows acceptable to good content validity. the 0.01 level (2-tailed). At first sight, this instrument seems to be adequate and useful to assess the perception of healthcare professionals concerning the illness of an individual patient. Further exploration of the psychometric properties of this questionnaire, i.e. validation in different groups of healthcare 158. A PRE-POST TEST PILOT TRIAL OF COMPRESSION professionals, is warranted. This next step has been started now. GLOVES IN EARLY INFLAMMATORY AND RHEUMATOID Disclosure statement: The authors have declared no conflicts of ARTHRITIS interest. Alison Hammond1, Yeliz Prior1, Vivienne Jones1, Mary Dooley2, Yvonne Hough3 and Angela Jacklin4 1 157. EXAMINING PERSONALITY TRAITS, COPING STYLES Centre for Health Sciences Research, University of Salford, Salford, 2Occupational Therapy, Southport & Formby District Hospital, AND ADJUSTMENT IN RHEUMATOID ARTHRITIS PATIENTS: A 3 PILOT STUDY Southport and Occupational Therapy, St Helens Hospital, St Helens, 4Occupational Therapy, Stepping Hill Hospital, Stockport, UK Fani Avgoustaki1, Rachel Gillibrand1 and Caroline A. Flurey1 1Health and Applied Sciences, University of West of England, Bristol, Background: Compression gloves are increasingly provided by Bristol, UK occupational therapists (OTs) to people with RA. Gloves are provided to: reduce hand joint pain (day and/or night), swelling and stiffness; Background: Previous research has not investigated the interplay of and improve hand function. A systematic review identified only four personality traits and coping strategies in relation to RA patients’ trials (n ¼ 8–24), of poor/moderate quality, indicating glove-wear may adjustment. The aim of this research was to explore potential lead to small reductions in proximal interphalangeal joint (PIPJ) associations between personality traits, coping strategies and adjust- swelling but effects on hand symptoms and function are unclear. ment with RA patients. The aim of the study was to evaluate the effects of compression gloves Methods: A mixed methodology design was employed. RA patients on hand symptoms and function to assist in planning a randomized (self-reported diagnosis) completed measures of adjustment controlled trial. [Abbreviated Injury Scale (AIS) and visual analogue score (VAS)], Methods: A pre-post-test study was conducted. Participants were coping styles [Eysenck Personality Questionnaire (EPQ)] and person- recruited from 10 rheumatology OT departments; had recent-onset ality traits [Medical coping modes questionnaire (MCMQ)] and an inflammatory arthritis/RA or RA. There were no steroid injections in i112 Wednesday 29 April 2015 POSTER VIEWING II

4/52; and no new/changed medication in 12/52, unless recent-onset physiotherapists were highly experienced (60% had at least 15 inflammatory arthritis/RA. Participants wore right and/or left Isotoner years of clinical experience). The majority of UK physiotherapists were three-quarter finger gloves, day and/or night as required. Assessments female (77%) and worked in the National Health Service (65%). 62% of at 0 and 4 weeks included: hand pain on activity and at night, hand Australian physiotherapists were male and 65% worked in private stiffness (all 0–10 numeric rating scales: none to very severe); swelling practice. A package of treatment incorporating advice, exercise and (joint circumference: cm); composite finger flexion to distal wrist other non-pharmacological modalities (e.g. hip manipulations/mobili- crease (CFF: cm); Measure of Activity Performance-Hand (MAP- zations (>60%) and gait re-education (>60%)) was recommended by HAND); and the Grip Ability Test (GAT). OTs were trained in conducting the majority. Different types of exercise were used, most commonly standardized assessments. Inter-rater reliability (ICC,11) was good: strengthening exercises (>90%). UK physiotherapists were more likely 2nd PIPJ circumference (0.91); CFF (0.76–0.93); GAT (0.98). Data were to provide range of movement exercises (91% vs 67%) and analysed using paired t-tests and effect sizes calculated using eta- proprioception exercise (76% vs 59%) than Australian physiothera- squared (>0.14, large effect). pists, who were more likely to include functional task training (74% vs Results: There were 41 participants (early inflammatory arthritis/RA, 48%) and hydrotherapy (65% vs 36%). Australian physiotherapists 14; RA, 27), including 33 women and 8 men with a mean age of 59.10 provide more treatment sessions than their UK colleagues (5 or more (S.D. 12.54) years and time since diagnosis of 2.33 (IQR 0.23–8.5) years. treatment sessions: reported by 75% and 40% of Australian and UK Seven (with early inflammatory arthritis) had medication changes in 12/ physiotherapists, respectively). Nearly all physiotherapists reported 52. Early inflammatory arthritis and RA results were combined as that they would monitor exercise adherence, but fewer than 25% use similar (Table 1). exercise diaries to do so. Conclusion: Compression gloves led to significant improvements in: Conclusion: This is the first international survey exploring how pain (day/night), stiffness, swelling, finger flexion and hand function, physiotherapists manage patients with hip OA. In the UK and with moderate to large effect sizes, although PIPJ swelling changes Australia, physiotherapists commonly provide a package of care for were small. The lack of a control group means improvements may not patients with hip OA that is broadly in line with current guideline be due to compression gloves. A randomized controlled trial is recommendations. There are some differences in clinical practice required, including longer follow up. between the two countries, but whether these differences impact on Funding statement: This work was supported by the Dowager clinical outcomes remains unknown. Eleanor Peel Trust and unrestricted educational grants from Jobskin Disclosure statement: M.A.H. has received research funding from the UK and Promedics Orthopaedics Ltd. NIHR School for Primary Care Research. N.E.F. and C.D.M. are Disclosure statement: The authors have declared no conflicts of supported by a NIHR Research Professorship award. All other authors interest. have declared no conflicts of interest.

158 TABLE 1. Mean (S.D.) outcomes pre- and post-4 weeks of compression glove a 160. PEOPLE’S VIEWS, BELIEFS AND EXPERIENCES OF wear EXERCISE FOR CHRONIC HIP AND KNEE PAIN: A COCHRANE Outcome measure 0 weeks 4 weeks P-value Effect size REVIEW WITH QUALITATIVE SYNTHESIS Hand pain on activity (0–10) 5.69 (2.13) 4.67 (2.32) 0.006 0.18 Mike Hurley1, Kelly Dickson2, Hanan Hauari2, Nicola Walsh3, Hand pain at night (0–10) 4.26 (3.26) 3.41 (2.30) 0.03 0.12 Sandy Oliver2, Jo Cumming4 and Robert Grant5 Hand stiffness (0–10) 5.51 (2.61) 3.92 (2.25) 0.001 0.33 1 2nd PIPJ circumference, cm 6.66 (0.58) 6.57 (0.55) 0.03 0.12 School of Rehabilitation Sciences, St George’s, University of CFF Middle finger, cm 5.45 (1.66) 4.88 (1.35) 0.002 0.23 London, 2Department of Childhood, Families and Health, Institute of MAP-HAND 21.91 (7.83) 19.78 (7.36) 0.02 0.12 Education University of London, London, 3Allied Health Professions, GAT 39.44 (20.82) 32.73 (2.86) 0.005 0.20 University of the West of England, Bristol, 4Nonprofit Organization 5 aRight hand only (n ¼ 38).CFF: composite finger flexion to distal wrist crease; GAT: Management and Centre for Health and Social Care Research, St grip ability test; MAP-HAND: Measure of Activity Performance-Hand; PIPJ: George’s, University of London, London, UK proximal interphalangeal joint. Background: Exercise improves chronic joint pain and its negative effects on physical function. The effect of exercise on psychosocial 159. HOW DO UK AND AUSTRALIAN PHYSIOTHERAPISTS function (health beliefs, depression, anxiety and quality of life) is less MANAGE PATIENTS WITH HIP OSTEOARTHRITIS? RESULTS well appreciated. This could be improved by understanding better the OF AN INTERNATIONAL CROSS-SECTIONAL inter-relationship among pain, physical and psychosocial function, and QUESTIONNAIRE exercise. To do this we conducted a qualitative synthesis of studies reporting people’s views, beliefs, feelings and experiences of chronic Melanie A. Holden1, Nadine E. Foster1, Christian D. Mallen1, joint pain and exercise. Linda Chesterton1, Rebecca Case1, Nicola Halliday1, Libby Methods: Forty-eight clinical, public health, psychology, social care N. Spiers2, Martyn Lewis1, Jonathan G. Quicke1, Rana S. Hinamn2 databases and relevant resources were searched. Two reviewers and Kim L. Bennell2 independently extracted data, used thematic analysis to match data 1Arthritis Research UK Primary Care Centre, Keele University, Keele, against a conceptual framework and identified broad themes and UK and 2Centre for Health, Exercise and , University subthemes. Reviewers compared their individual coding, considered of Melbourne, Melbourne, Australia the extent to which each sub-theme was mutually exclusive and how they understood the data in relation to their individual coding. Background: Hip OA is a common painful and disabling condition. Results: Nine studies met the inclusion criteria. Their design, Physiotherapists play an important role in managing patients with hip methodological rigour and reporting was good with clear descriptions OA, however, little is currently known about their management of their methodology, clearly reported their findings, and the authors approaches and whether these differ internationally. had taken precautions to ensure transparency and minimize potential Methods: We conducted an international, cross-sectional survey in bias. Synthesis of the studies showed that pain affected all domains of the UK and Australia. In the UK, the survey was mailed to 3126 people’s lives, and there is a very complex inter-relationship among physiotherapists who were either members of one of two Professional pain, physical and psychosocial function, and health beliefs. People’s Networks of the Chartered Society of Physiotherapy, or based within health beliefs about chronic pain shaped their attitudes and beha- the Central England (North spoke) and North West Primary Care viours. They often associated physical activity with the onset and/or Research Networks. In Australia, a link to an online survey was increase in pain, and interpreted this as activity-induced joint damage. distributed to physiotherapists nationally, including via email news- As a consequence people refrained from activity for fear of causing letters of the Australian Physiotherapy Association. The survey additional harm (fear-avoidance behaviour). Few people had received explored physiotherapists’ reported management of a patient with advice about the safety and value of exercise in the management of hip OA using a case vignette and clinical management questions. It chronic joint pain. Very few had participated on exercise programmes, also captured demographic and practice data. Descriptive statistics but those who had tended to have positive experiences which altered were used to summarize physiotherapists’ characteristics and their beliefs and understanding about the safety of exercise and its reported management of the vignette patient. Statistically significant utility in the management of joint pain. differences in clinical practice between the UK and Australia are Conclusion: To improve uptake and effectiveness of exercise presented, based on logistic regression models adjusted for gender programmes we need to provide better information about the safety and clinical experience (P < 0.001). and benefits of exercise, tailor exercise to ensure they are relevant to Results: The survey response rate was 53% (n ¼ 1646) in the UK, with people’s needs, challenge unhelpful health beliefs, provide practical 1148 physiotherapists reporting having treated a patient with hip OA in support explaining what, how and when to exercise. the last 6 months. These, along with 207 Australian physiotherapists Disclosure statement: The authors have declared no conflicts of who responded, were included in the analysis. Overall interest. POSTER VIEWING II Wednesday 29 April 2015 i113

161. THE PHYSICAL AND PSYCHOSOCIAL EFFECTS OF statistically significant changes were seen in the two smaller groups. EXERCISE ON CHRONIC HIP AND KNEE PAIN: A COCHRANE There was also only a statistically significant difference for the largest REVIEW WITH META-ANALYSIS group (n ¼ 12) in the LupusQol subscales of physical health (P ¼ 0.008) 1 2 3 3 between T1 and T2, and the subscale fatigue between T1 and T3 Mike Hurley , Nicola Walsh , Sandy Oliver , Kelly Dickson , (P ¼ 0.043). For the Impact of Health Education Questionnaire (HEIQ) A Hanan Hauari3, Jo Cumming4 and Robert Grant5 1 statistically significant improvement was seen in the category skills School of Rehabilitation Sciences, St George’s, University of and technique acquisition between T1 and T2 (P ¼ 0.032) for the larger London, London, 2Allied Health Sciences, University of the West of 3 group only. There were no statistically significant changes in any of England, Bristol, Department of Childhood, Families and Health, these measures for either of the two smaller groups. Differences were Institute of Education, University of London, 4Freelance Consultant, 5 also noted between those that attended five or more of the weekly Nonprofit Organization Management and Centre for Health and sessions and those that attended four or less sessions. Table 1 shows Social Care Research, St George’s, University of London, London, UK significant differences in total scale and subcategory scores. Conclusion: The results indicate that group size appears to affect the Background: Chronic peripheral joint pain is extremely prevalent and outcomes of FAME, with the largest group showing more significant a major cause of physical and psychosocial problems. Exercise results. This may be due to increased opportunities for peer discussion improves pain and physical function, but the effect of exercise on of effective fatigue management strategies and peer-modelling in the psychosocial function (health beliefs, depression, anxiety and quality larger group. Group attendance of five or more sessions also appeared of life) is less well appreciated. To improve our understanding of the to affect FAME outcomes. This underlies the importance of motivating inter-relationship among pain, physical and psychosocial function and participants to attend a minimum of five sessions. However, a larger exercise, we conducted a Cochrane Review with meta-analysis of scale study is needed to confirm these findings. clinical trials that reported the effect of exercise interventions on Disclosure statement: The authors have declared no conflicts of psychosocial variables. interest. Methods: Forty eight clinical, public health, psychology, social care databases and other relevant resources were searched. References of included studies were checked for relevant studies. Key experts were 162 TABLE 1. Scales and scale: categories with significant differences in number of asked about unpublished studies. Four of the authors independently sessions attended assessed studies against inclusion/exclusion criteria and methodolo- Scale or scale category Time points P-value gical quality, and entered extracted data into a database. Quantitative HADS Depression T1 and T3 0.005 synthesis of randomized controlled clinical trials of exercise-based HADS Anxiety T2 and T3 0.023 rehabilitation programmes was conducted. Total score of Stanford Self-efficacy Scale T1 and T2 0.046 Results: Twenty-four trials (2640 participants) met the inclusion Lupus QoL Burden to others subscale T1 and T3 0.023 criteria. There were large variations in programme’s content, mode Lupus QoL Fatigue subscale T1 and T2 0.036 of delivery, frequency and duration outcomes measured, methodolo- HEIQ Skill acquisition subscale, Lupus QoL T1 and T3 0.011 Fatigue subscale gical quality and reporting. The design and reporting of most studies HEIQ Skill acquisition subscale T1 and T2 0.002 was moderate/good, though some were ambiguous, complex and HEIQ Skill acquisition subscale T1 and T3 0.011 difficult to understand. Many trials had small sample sizes and short HEIQ Self-monitoring and Insight subscale T1 and T2 0.026 follow up (less than 6 months). Exercise meta-analysis results HEIQ Constructive attitudes and approaches subscale T1 and T3 0.041 (presented as number of studies, standard mean deviation (95% CI) HADS: Hospital Anxiety and Depression Scale; HEIQ: Health Education Impact and% heterogeneity): reduced pain [n ¼ 16; 0.25 (0.41, 0.09); Questionnaire; QoL: Quality of Life. 61%]; improved physical function [n ¼ 13; 0.22 (0.36, 0.08); 38%]; self-efficacy [n ¼ 9; 0.46 (0.27, 0.64); 44%]; depression [n ¼ 5; 0.18 (0.31, 0.04); 31%]; anxiety [n ¼ 1; 0.10 (0.27, 0.06); 0%]; health- related quality of life measured by SF-36; mental health [n ¼ 4; 2.90 163. DEVELOPMENT AND DELIVERY OF A (0.15, 5.65); 36%]; social function [n ¼ 4; 6.58 (2.78, 10.38); 0%]; role PHYSIOTHERAPY-LED EXERCISE PROGRAMME FOR USE IN emotional [n ¼ 4; 1.20 (–4.12, 6.53); 54%] and vitality [n ¼ 4; 3.90 (0.55, A RANDOMIZED CONTROLLED TRIAL WITH PATIENTS WITH 7.25); 15%]. SHOULDER IMPINGEMENT SYNDROME Conclusion: Exercise not only improves pain and physical function, Kay Stevenson1, Sue Jackson2, Julie Shufflebotham1, but also has moderate benefits on psychosocial functioning and Edward Roddy1 and Nadine Foster1 quality of life. Heterogeneity in the programmes and lack of well- 1Arthritis Research UK Primary Care Centre, Keele University and designed trials with psychosocial variables as the primary outcome 2Trauma and Orthopaedics, University Hospital of North Midlands, impedes our understanding. Studies are needed that have psychoso- Stoke-on-Trent, UK cial variables as primary outcomes. Disclosure statement: The authors have declared no conflicts of Background: Shoulder pain affects one in three adults in their lifetime. interest. Subacromial impingement syndrome (SIS) is one of the most common diagnoses, and is thought to be caused by bony abnormalities, 162. IMPACT OF GROUP SIZE ON OUTCOMES OF A weakness or instability in the rotator cuff muscles, scapular instability FATIGUE AND ACTIVITY MANAGEMENT EDUCATION or poor posture. While general exercise and steroid injection are PROGRAMME FOR INDIVIDUALS WITH SYSTEMIC LUPUS thought to be beneficial for patients with SIS, a factorial randomized ERYTHEMATOSUS controlled trial (the SUPPORT trial) has been testing the effect of US- guided vs unguided steroid injection and physiotherapy-led exercise Deirdre Connolly1,2 and Ruth O’Riordan2 1 2 vs an advice leaflet. Here we summarize the development and delivery Occupational Therapy, Trinity College and Occupational Therapy, of the physiotherapy-led exercise programme within the SUPPORT St James Hospital, Dublin, Ireland trial. Methods: Clinical consensus on the most frequently used exercises Background: Fatigue is one of the most prevalent symptoms of SLE for SIS and practice guidelines from the Chartered Society of affecting up to 90% of individuals. Previous studies report that fatigue Physiotherapy were used to develop the treatment protocol with 10 management strategies are mainly self-learned with little input from experienced physiotherapists. A clinically applicable exercise pro- health professionals. A Fatigue and Activity Management Education gramme was developed that incorporated three key stages of (FAME) programme was therefore developed for people with SLE. progression: stage 1, achieving scapular stability; stage 2, range of FAME is a 2-h programme run over 6 weeks. The weekly sessions motion exercises with scapular stability; and stage 3, resistance consist of an educational component, group discussions, and weekly exercise. The treatment protocol stipulated that patients should be goal setting and review. Three FAME programmes were run seen within 3 weeks of randomization, receive a 40-min initial consecutively with four, six and 12 participants respectively. assessment with between 6 to 8 follow-up treatment sessions of Methods: A quasi-experimental design was used to measure the 20 min. A 2-day training programme was developed for 22 participat- impact of FAME. Outcome measures of fatigue, quality of life, mood, ing physiotherapists which included an overview of current evidence, impact of health education and self-efficacy were administered the SUPPORT trial design, exercise adherence and motivational immediately before FAME (T1), immediately after (T2) and eight techniques. Particular emphasis was placed on patient assessment, weeks later (T3). prescription of an individualized exercise programme, supervision and Results: On examining the impact of group size, there was a progression. statistically significant decrease in Fatigue Severity Scale (FSS) Results: 128 patients with SIS were randomized to receive the between T1 and T3 (P ¼ 0.035) in the largest group (n ¼ 12). No physiotherapy-led exercise intervention. In total, 81% (n ¼ 99) had their i114 Wednesday 29 April 2015 POSTER VIEWING II

first physiotherapy session within three weeks from randomization. The mean number of treatment sessions attended was 5.2 (S.D. 2.5) and the majority (96%) had a 40 min initial appointment. The most HEALTH SERVICES RESEARCH, popular exercise in Stage 1 was scapular setting with glenohumeral ECONOMICS AND OUTCOMES joint (GHJ) flexion, in stage 2 was a GHJ medial rotation stretch and in stage 3 was scapular setting through active lateral rotation. RESEARCH Supervision of the exercise programme occurred in almost all treatment sessions (92%). Conclusion: Expert clinical consensus and national guidelines were used successfully to design, develop and deliver a physio- 165. A PATIENT SURVEY TO ASSESS VIEWS ON therapy-led exercise intervention for patients with SIS in the MEDICATION IN INFLAMMATORY ARTHRITIS SUPPORT trial. Key features of the exercise intervention included 1 1 1 1 individualization, supervision and progression over three exercise Reema Bhatt , Ognjenka Savanovic-Abel , Jon King , Owen Moore , 1 2 1 stages. The clinical results of the trial are the subject of a separate Mark Perry , Bashaar Boyce and Lindsay Robertson 1 abstract. Rheumatology, Plymouth Hospitals NHS Trust, Plymouth and 2 Disclosure statement: The authors have declared no conflicts of Rheumatology, Royal Devon and Exeter NHS Foundation Trust, interest. Exeter, UK

Background: Patients are routinely given counselling by a physician or 164. A COMPARISON OF THE INDICATORS OF HAND a nurse specialist prior to commencing DMARD or biologic therapy. An FUNCTION IN EARLY RA POPULATIONS FROM THE UK AND appropriate patient information leaflet always supports information CHINA given. Despite this, anecdotally on follow up, patients seemed to Bowen Su1, Luan Xue2, Qing Ma3 and Jo Adams1 lack knowledge regarding significant risks and side effects of their 1Faculty of Health Sciences, University of Southampton, medications. This posed potential risks to their health hence this Southampton, UK, 2Department of Rheumatology, Yueyang Hospital survey was conducted to highlight problem areas. of Integrated Traditional Chinese and Western Medicine, Shanghai Methods: A paper survey was given to patients in the outpatients University of Traditional Chinese Medicine and 3Yueyang Hospital of department of two regional hospitals. This anonymous survey Integrated Traditional Chinese and Western Medicine, Shanghai consisted of 21 questions including diagnosis, whether they felt University of Traditional Chinese Medicine, Shanghai, China sufficient information was given prior to treatment initiation and questions on potential risks and side effects of their medication. Background: RA is a universal disease with clinical presentations and Results: In total 124 questionnaires were completed. 110 patients impacts varying in different ethnic groups. The process of inflamma- were on DMARDs and 39 on biologics. 79/124 (63.7%) patients had tory joint damage quantified by ESR, CRP and the number of tender been on their treatment longer than three months. 106/124 (85.5%) and swollen joints can lead to structural impairment and deformity of patients thought they had sufficient information provided to them wrists and hands. However, the relationship between hand impairment before starting this treatment, 2/124 (1.6%) disagreed and the rest did and disability in early RA is controversial. A comparison of this not answer the question. 42/110 (38.2%) patients on DMARDs relationship in different population groups would add to the under- expected it would take 1–3 months before they noticed symptom standing of country-specific impacts of RA. This study compared the improvement. 97/110 (88.2%) patients on DMARDs always took correlations of disease activity and hand impairment with self-report medication regularly with the remainder sometimes forgetting. 55/ hand function between two early RA populations from the UK and 110 (50%) were aware they should not have live vaccines while on a China. DMARD in contrast to 36/39 (92.3%) of those on biologics. Of the Methods: A cohort comparison study was conducted. 60 Chinese patients on MTX or LEF, 8/78 (10.3%) thought it was safe to become patients recruited from Shanghai, China were matched on gender and pregnant or father a child while on this medication and 6/78 (7.7%) age with 60 patients from a prospective early RA cohort from the UK considered it safe to drink more than 20 units of alcohol per week; (SARAH trial). The procedures of data collection in China followed the 74/78 (94.9%) were aware that they should report any worsening of standard operating procedures employed in the SARAH trial. Outcome breathing or dry cough to their doctor. 35/39 (89.7%) patients on measures including a medical health questionnaire, medical history biologics were aware that they should stop the biologic if they develop and physical assessments were used to assess disease activity, hand infection. 4/7 (57.1%) of patients on rituximab were aware of the risk of impairment and function. progressive multifocal leucoencephalopathy (PML). Results: There was no significant association (P > 0.05) between Conclusion: This survey highlights that patients do not always retain hand function with MCP joint deformity in either population group. important information from an appropriate drug counselling service. Correlations between hand function with range of movement We are concerned that a significant proportion of patients were not measured by active wrist flexion, combined finger flexion and aware of the risks with live vaccines or those related to pregnancy composite finger extension were weak in both the UK and Chinese while taking MTX or LEF. Patients on biologics overall seemed to be population (r < 0.04, P < 0.05). The associations between self-report more aware of the risks but not of those related to rituximab and PML. overall hand function and full grip strength were moderate to weak A need for improvement is clear and this could be achieved by in Chinese patients (dominant r ¼ 0.473, non-dominant r ¼ 0.347; ensuring that patients attend counselling sessions with a relative or P < 0.05). The correlations were weak between overall hand func- friend, re-education after a certain time period or reminder leaflets at tion and pinch grip among Chinese patients (P < 0.05). However, regular intervals. Health professionals should be mindful of these correlations between hand function and full grip strength were issues and address them at follow-up appointments. Patient education moderate in UK patients (dominant r ¼ 0.582 and non-dominant is paramount when commencing new treatment and these results r ¼ 0.555; P < 0.05). Moderate relationships were found between show there is a room for improvement in reducing patient harm. hand function and pinch strength in the UK patients (dominant Disclosure statement: The authors have declared no conflicts of r ¼ 0.647, non-dominant r ¼ 0.624; P < 0.05). There were strong interest. to moderate negative correlations between hand function and pain in both population groups (UK r ¼0.690, China r ¼0.458; 166. IMPACT OF INTRODUCTION OF INTEFERON GAMMA P < 0.05). A moderate negative correlation was found between hand RELEASE ASSAY (T SPOT) PRIOR TO BIOLOGIC THERAPY IN function and swelling (r ¼0.45; P < 0.001) and a moderate GWENT correlation between dexterity and hand function (dominant r ¼ 0.441, non-dominant r ¼ 0.440; P < 0.05) was found between Abeer S. Ghuman1, Gina Jones1, Annette Haggett1, Sue Hanson2 hand function and swelling or hand function and dexterity among and Sara Carty3 UK patients. 1Rheumatology and 2Pharmacy, Nevill Hall Hospital and Conclusion: In early RA populations in both the UK and China, hand 3Rheumatology, St Woolos Hospital, Newport, UK strength, range of movement and pain are indicators of hand function. There is a weaker correlation between hand strength with self-reported Background: Anti-TNF therapy increases the risk of reactivation of hand function in the Chinese population compared with the UK RA tuberculosis (TB). Pre-treatment screening should include a clinical patients. Swelling is not an indicator of hand function in the UK examination, history of any prior TB, a chest radiograph and, if appro- population. priate, a tuberculin skin test (TST). For patients on immunosuppressive Disclosure statement: The authors have declared no conflicts of therapy, a TST is not helpful due to false negatives. Therefore for interest. immunosuppressed patients British Thoracic Society (BTS) guidelines POSTER VIEWING II Wednesday 29 April 2015 i115

recommend an individual risk assessment is made; if the annual risk of is a positive one, and many participants have an altruistic attitude TB is greater than the risk of drug-induced hepatitis, then chemopro- towards clinical research; however when explained in detail about the phylaxis should be given. Currently the role of more sensitive T-cell IFN-g impact of a certain study on their personal care plan (such as the risk of release assays (IGRAs) for screening is unclear. The aim was to getting placebo, unavailability of an useful medication at the end of the determine if IGRA testing picked up any patients who were at risk of trial, the need to attend intense and time-consuming study visits), the developing TB not picked up by initial screening and risk assessment. patients’ views might change. As our questionnaire gave a subjective Methods: Patients who were starting or switching anti-TNF therapy assessment of a limited population sample, we accept that there are from June 2012 onwards had an IGRA test done. The annual risk of many other personal reasons difficult to explain or explore that might developing TB vs risk of chemoprophylaxis was calculated. have driven the participants’ responses. The authors do not claim that Recommendations from this risk assessment were compared against the results of the study could be generalized and further research their IGRA test result and whether they went on to develop TB. (multicentre study or larger patient group) is definitely needed. Results: 49 patients were identified. 43 patients had a negative IGRA Disclosure statement: The authors have declared no conflicts of test and all had low risk of developing TB when compared with their interest. risk from chemoprophylaxis. None of these patients have developed TB to date (Average length of treatment 18.2 months). Three patients 168. SYMPTOM ONSET AND HELP-SEEKING TRAJECTORY had a positive IGRA (6%), 1 of these patients had an abnormal chest OF PATIENTS WITH RHEUMATOID ARTHRITIS radiograph and would have been investigated and treated for latent TB regardless of this result. One patient had previously been treated with Diederik De Cock1, Kristien Van der Elst2,3, Veerle Stouten2, anti-TNF and not developed TB had positive IGRA testing when Donna Peerboom1, Sabrina Meyfroidt1, Johan Joly2, changing therapy. He was treated with chemoprophylaxis. He would Rene Westhovens1,2 and Patrick Verschueren1,2 also have been treated empirically according to BTS guidelines. The 1Skeletal Biology and Engineering Research Centre, KULeuven, third patient was treated with chemoprophylaxis prior to anti-TNF 2Rheumatology, University Hospitals Leuven and 3Centre for Health therapy based on their positive IGRA result. According to risk Services and Nursing Research, KULeuven, Leuven, Belgium assessment, this patient’s risk of TB was lower than the risk of chemoprophylaxis and so would not have received chemoprophylaxis Background: Delay between symptom onset and treatment initiation prior to anti-TNF therapy according to the BTS guidelines. The patient influences RA disease outcome on the longer term. The ideal threshold had a borderline positive test and is under review by the chest to treat patients with RA in a timely fashion is set at 12 weeks after physicians; and other patients had a negative IGRA test and would symptom onset. In a previous study, we demonstrated that treatment have been treated with chemoprophylaxis according to BTS guidelines was initiated within this time window in only one in five patients in but were not as a result of a negative T spot test. Belgium. Median delay was 23 weeks. Patient-related delay contributed Conclusion: T spot testing in our population has picked up one patient the most to treatment delay. We aim to explore the nature of the first who would not have been treated according to BTS guidelines. Two symptoms of RA and patients’ reasons for help-seeking, their help- patients have avoided chemoprophylaxis. The test costs approxi- seeking trajectory and the influence of these factors on treatment delay. mately £150. T spot testing is reported to have a sensitivity of 96% and Methods: Data of 94 DMARD-naive early RA patients were collected a specificity of 99%. It is unlikely that IGRA assay is a cost-effective in 1 academic centre between January 2009 and April 2013. These method of screening in a low risk Welsh population. patients participated in the CareRA study, a multicentre randomized Disclosure statement: The authors have declared no conflicts of controlled trial to optimize RA treatment. In the context of the CareRA interest. trial, date of symptom onset, RA diagnosis and treatment initiation were collected, besides demographic and clinical characteristics. Time of symptom onset, first visit to their general practitioner (GP) and 167. CLINICAL TRIALS PERCEPTION IN RHEUMATOLOGY referral date were reported previously by their GP. In the present study, PATIENTS: EXPERIENCE FROM A SINGLE RHEUMATOLOGY the patients were interviewed about their initial RA-related symptoms TERTIARY CENTRE during a follow-up clinical visit between November 2012 and August Coziana Ciurtin1, Maria Leandro1, Halina FitzClarence1 and 2014 by two study coordinators, using a self-developed assessment David A. Isenberg1 form. Treatment delay was defined as the period between symptom 1Department of Rheumatology, University College London, onset and treatment initiation, patient delay as the period between London, UK symptom onset and first contact with a healthcare professional as reported by patient/GP. All patients gave their informed consent. Background: Over the last decade there has been a huge increase in Ethical approval was granted for the CareRA trial. the available therapies for chronic rheumatic conditions. The dis- Results: Of the 94 participants, 75% were women; with a mean (S.D.) age 2 covery, testing and implementing of these therapies was enabled by of 52 (14) years and BMI of 27 (4) kg/m . RF was positive in 62% and numerous clinical trials which exposed the rheumatology patients ACPA in 73%, 26% had erosions and a mean (S.D.) DAS for 28 joints more than ever to the challenges of clinical research. No previous (DAS28)-CRP of 5 (1) mg/l was noted at baseline. As the first RA symptom, reports have investigated the perception and willingness of rheuma- 91% of patients reported painful joints, 73% swollen joints, 51% rigid tology patients to participate in clinical trials. joints, 21% fatigue and 33% morning stiffness. Furthermore, some Methods: We conducted a cross-sectional survey of rheumatology patients emphasized a loss of physical strength and redness in the patients using a questionnaire, which comprised two demographic affected joints. The most important reason to visit a healthcare questions, two 5-point Likert opinion questions, 19 true/false/unsure professional was having too much pain (90%). The GP was the most knowledge questions and one open question addressing what would frequently contacted healthcare professional after symptom onset (86%). help the participant to gain a better understanding about clinical trials. Median (IQR) treatment delay was 26 (17–50) weeks. Only 14% of patients Results: Eighty-five patients returned the questionnaires (response were seen in 12 weeks. Patient-reported (response rate of 93%) median rate 84.1%). The mean number of correct answers to the 19 (IQR) patient delay was 4 (0–8) weeks while the GP-reported (response knowledge questions was 10.5 2.87. Patients with higher vs lower rate of 37%) median (IQR) patient delay was 9 (1–30) weeks. level of education had significantly higher knowledge scores (mean Conclusion: Treatment delay remains an issue in RA care. Pain is the correct answers 59.4 13.1 vs 39.8 20.4, P ¼ 0.013). They also most prevalent initial symptom and most important reason to visit a expressed greater willingness to take part in research (87.5% vs healthcare professional, in most cases the GP. Further research should 48.2%, P < 0.001). The patients who agreed to participate in research study patients’ help-seeking behaviour in depth, especially the trajectory provided significantly more correct answers (59.4 15.3% vs of those patients not experiencing pain as the primary initial symptom. 47.7 27.2%, P ¼ 0.032). Poor disease control as the main reason to Disclosure statement: P.V. holds the Pfizer Chair for the join a clinical trial correlated well with patients’ previous participation in Management of Early Rheumatoid Arthritis. All other authors have research (r ¼ 0.71; P < 0.05). Paradoxically, the lack of understanding declared no conflicts of interest. of research principles (defined as <50% correct answers to the knowledge questions) correlated positively with willingness to partici- 169. SETTING UP AN INDEPENDENT PATIENT GROUP TO pate in clinical trials (r ¼ 0.72; P < 0.05). IMPROVE AND DRIVE CHANGE IN RHEUMATOLOGY Conclusion: The results of our study revealed that patients lack OUTPATIENT SERVICES: AN EVALUATION information about clinical trials as the correct response rate was only slightly above 50%, and that they had a moderate willingness to take Savia de Souza1,2, Carol Simpson1,2, James Galloway1,2, part in clinical trials. The need for educational programmes about clinical Sophia Steer2, Joanne Dobson2, Radka Chura2, Patience Duffort1 research was highlighted by the participants to the survey. Our and Heidi Lempp1 paradoxical finding that better knowledge about research correlated 1Academic Rheumatology, King’s College London and with less willingness to take part in research merits particular attention. 2Rheumatology, King’s College Hospital NHS Foundation Trust, We hypothesize that the general perception about taking part in research London, UK i116 Wednesday 29 April 2015 POSTER VIEWING II

taking LEF and 1 patient was taking MMF. Contacted group of patients Background: Patient-public involvement is gaining increasing impor- (39 or 47%): 20 patients had RA (51%); 13 patients had PsA (33%); 4 tance within the National Health Service (NHS) to ensure that services patients had unclassified inflammatory arthritis (10%); and 2 patients delivered are relevant to patients’ needs. The Academic Rheumatology had a CTD (5%). Contacted group of patients (39 or 47%): 36 patients Department at King’s College London has a longstanding record of (92%) on MTX, 3 patients (8%) on LEF.2 patients reported meno- involving patients (as patient experts) in research and teaching. In pause.2 patients had had a hysterectomy. Of the 35 remaining 2013, Rheumatology Outpatients staff at King’s College Hospital patients, 18 (51%) said they were on contraception. Six patients used expressed an interest in establishing a patient group to help with a contraceptive pill, five patients used an IUD, three patients organizational difficulties and suggest improvements on how best to sterilization and four patients -condoms. All 39 patients (100%) said advance rheumatology outpatient services within the NHS Foundation they had been given advice on the need to avoid pregnancy while Trust; thus extending patient involvement at King’s into health service taking their medication. Thirty-one patients (79%) remember being delivery. given written as well as verbal advice on contraception. Eight patients Methods: The Independent Patient Group (IPG) was set up as part of a (21%) remember given verbal advice only. larger project to improve patient services (funded for 1 year by an Conclusion: 100% of patients recalled being given advice that they external organization). 10 patients (predominantly female, aged 29–67 should not get pregnant while taking the DMARD. 79% of patients years, of various ethnicities and with a range of rheumatic conditions) acknowledged given written and verbal advice. 44% of patients were recruited by clinic nurses and contacted by the two group co- reported not currently using contraception. The guidelines state that chairs (both departmental patient experts) to agree to terms of reliable contraception should be used when on LEF and this audit reference for the group. 12 meetings were held between January and identified patients who were taking LEF were not on reliable contra- October 2014. Agendas were drawn up by the co-chairs based on ception. We would recommend that clinicians consider a patient’s clinic observation and personal experiences of IPG members. Minutes childbearing potential when prescribing a DMARD. Advice regarding were taken at meetings and sent to clinic staff and management. IPG DMARDs and pregnancy is mandatory when prescribing to women of members evaluated the meetings quarterly and were remunerated for childbearing age. Ensure women being prescribed LEF are on reliable their participation. contraception. Review regularly the patient’s awareness that preg- Results: Mean attendance at IPG meetings was 62%. Evaluation of nancy is contraindicated while taking MTX, LEF or MMF—the meetings showed they were well received (mean rating 7.5/10) with commonest DMARDS used. patients frequently citing them useful for learning what is happening in Disclosure statement: The authors have declared no conflicts of the rheumatology department (research and clinic), plans for service interest. improvement and hearing the views of other patients. Based on IPG feedback; a 13-point action plan was drawn up by clinic staff to discuss the points raised, who is responsible to rectify organizational 171. PATIENT EXPERIENCE OF THE RHEUMATOLOGY shortcomings and by when to implement changes. Successful DEPARTMENT IN A DISTRICT GENERAL HOSPITAL outcomes included: an improved waiting experience (a reduction in mean clinic wait times (67% of patients were seen within 30 min of their Rozeena H. K. Garner1 and Ken Lim1 appointment time in September 2014 compared with 47% in 1Rheumatology, Kingsmill Hospital, Mansfield, UK September 2013), cleaner/tidier waiting area, more comfortable seating and clearer signs); improvements in (i) clinical services Background: The importance of patient experience has been high- (friendlier nursing staff and formalizing an annual review process for lighted in the Quality standard for patient experience in adult National patients) and (ii) allied services (longer opening hours for phlebotomy, Health Service (NHS) services (QS15) to guide commissioners to deliver a review of physiotherapy services provision for rheumatology patients a high-quality patient centred service. The Commissioning for Quality in and more timely delivery of home medication (92% of patients RA (CQRA) developed a patient-reported experience measure (PREM) to received their medication on time in October 2014 compared with assess patient experience for patients with rheumatic diseases. The 48% in June 2014). The IPG was also key in helping develop a new questions are based around elements outlined in the Department Of mobile application for the department and in formulating topics for a Health NHS Patient Experience Framework, National Institute for Clinical rolling programme of Patient Educational Evenings. Excellence QS15 and clinical guidance for RA. We report the results of Conclusion: Patients are interested in helping shape the services they the Commissioning for Quality in Rheumatoid Arthritis (CQRA) PREM receive. Through the IPG, patients have played an important and survey delivered to patients in the rheumatology department to assess active role in driving change and improving patient education and their experience at district general hospitals. access to services. Methods: We collected and analysed data for 135 participants Disclosure statement: The authors have declared no conflicts of attending the rheumatology department for more than one year at interest. two district general hospitals over a two week period using the CQRA PREMs questionnaire. Results: From our cohort of 135 participants, 56% were female and 170. DMARDS IN WOMEN OF CHILDBEARING AGE: ARE WE 92% Caucasian (age range 18 to >85 years). 77% had inflammatory FOLLOWING THE GUIDELINES? arthritis (94 RA), 5% CTD, 3% vasculitis, 3% PMR, 3% AS, 3% OA and 1% gout. 11% had secondary FM. 85–97% felt their needs and personal Charlotte Fisher1 and Thushani S. Wickramaratne1 preferences were considered. 82–92% felt they were familiar with 1Rheumatology, Queen’s Hospital, Romford, Essex, UK members of their team and how to access help. 83% felt they were able to approach their team about worries regarding treatment/life and 63% Background: DMARDs are crucial in achieving remission. Advice regarding personal/intimate relationship issues. 92–94% felt they were should be given before starting in woman of childbearing age. Many given information at the time they needed and had a good understanding DMARDs are contraindicated in pregnancy and it is essential to let of the treatments being offered. However, only 61% felt they were told women know of the need to avoid pregnancy. Auranofin, D- about patient groups/organizations and 35% felt they were offered the penicillamine, LEF, MTX, MMF and sodium aurothiomalate are opportunity to attend self-management programmes. 88% felt they had contraindicated in pregnancy. MTX should be discontinued 3 months enough time with their health care professional, 71% felt their condition before conception. LEF discontinued two years prior to conception, or, was controlled enough to get on with daily life and 76% were able to get undergo a washout prior to attempting to conceive. There was no help quickly in a flare. 19% had their clinic appointment cancelled recent audit done in our hospital whether patients are being given unexpectedly and 3% of these were rescheduled more than 12 weeks appropriate advice on pregnancy. Therefore, we decided to audit if we later. The remainder were rescheduled within 6 weeks. 36% required an are following the British Society for Rheumatology guidelines. extra consultation between routine appointments and 1% had this Methods: We included all female patients aged 18–50 years old on a appointment scheduled more than 12 weeks later (the remainder within 6 DMARD which is contraindicated in pregnancy, attending the weeks). 86% felt they had a good overall experience of the rheumatology rheumatology department at Queen’s Hospital from 1 November department. 2013 to 30 January 2014 (3-month retrospective). Cases were Conclusion: Patient experience is an important part of chronic identified using the shared rheumatology drive. Patients were disease management. Using the PREM questionnaire, we were able contacted on phone or when attended their outpatient rheumatology to demonstrate that overall patients had a good experience of the care appointments. they received in the rheumatology department. However, areas for Results: In all, 83 patients (19–49 years were identified. 39 patients improvement were highlighted, particularly relating to the opportunity (47%) were successfully contacted. Disease category of identified to access self-management groups and patient groups. This has been group (83 patients):46 patients had RA (55%); 21 patients had PsA addressed by promoting national patient organizations in the waiting (25%); 10 patients had unclassified inflammatory arthritis (12%); and 6 room to improve the quality of care we deliver. patients had a CTD (7%). DMARD category of identified group (83 Disclosure statement: The authors have declared no conflicts of patients):72 patients (87%) were taking MTX, 10 patients (12%) were interest. POSTER VIEWING II Wednesday 29 April 2015 i117

172. DEVELOPMENT AND PSYCHOMETRIC TESTING OF A of impact on all-cause mortality at 30 days and 1 year and second hip BRITISH ENGLISH VERSION OF THE DISABILITIES ARM fracture within 2 years. Each hospital was analysed separately and SHOULDER AND HAND QUESTIONNAIRE acted as its own control in a before-after time series design. Cox 1 1 2 regression modelling was used to describe the association between Alison Hammond , Yeliz Prior and Sarah Tyson the intervention and time to death. For the outcome of second hip 1Centre for Health Sciences Research, University of Salford, Salford 2 fracture, a competing risks survival model was used to account for the and Stroke & Vascular Research Centre, University of Manchester, competing risk of death. Meta-analyses were used to pool estimates Manchester, UK on each health outcome for similar interventions across hospitals in the region. Background: The Disabilities Arm Should and Hand (DASH) ques- Results: A total of 33 153 primary hip fracture patients were identified, tionnaire (developed in Canada) is a widely used outcome measure for of whom 1288 (4.2%) sustained a second hip fracture within 2-years, upper limb conditions, consisting of 30 items, 21 regarding daily and 3033 (9.5%) and 9663 (29.8%) died within 30 days and 1 year activity and 9 regarding impact of condition. The aim of this study was respectively. Overall, post-hip fracture mortality decreased markedly to develop a British English DASH and psychometrically test it in a UK across the region, from 33.2% to 25.5% dying within 1 year from 2003 population of people with RA. to 2012. In contrast, the proportion of patients sustaining a second hip Methods: The Institute of Work and Health (IWH) cross-cultural fracture remained stable throughout the study period. Pooled adaptation methods were followed: forward translation to British estimated impact of either an orthogeriatrician or FLS is presented in English; synthesis; expert review of equivalence; and cognitive Table 1. debriefing. Psychometric testing included internal consistency Conclusion: The coordination and organization of services for the care (Cronbach’s a); test-retest reliability [ICC (2,1)] and concurrent validity of hip fracture patients is challenging due to the multidisciplinary care (Pearson’s and Spearman’s correlations). Adults with RA were patients require. This study provides evidence that the introduction recruited from 17 Rheumatology outpatient departments, who com- and/or expansion of such services has a large beneficial effect on pleted two test booklets three weeks apart, including the DASH, subsequent mortality rates. Reassuringly the effect was consistent HAQ20, SF36v2 and numeric rating scales for disease activity, hand across hospitals and for interventions that occurred at different time pain, general pain and fatigue. points over the study period. It’s likely that these effects are partly a Results: During translation and equivalence review, changes to use reflection of wider underlying changes to a hospitals service delivery plain English and British English terminology were made (e.g. do not that led up to the successful implementation and change in hospital perform; jumper rather than pullover sweater). 31 people with RA were care model. There was no evidence for a reduction of second hip interviewed [age 63.42 (S.D. 12.04) years, RA duration 15.71 (S.D. 12.61) fracture, but the effect on non-hip fractures remains unanswered, as years]. All DASH items were considered understandable and relevant. these outcomes cannot be ascertained within the secondary care 340 completed the test 1 booklet: 251 women, 89 men; mean age 62 setting of this study. (S.D. 12) years; RA duration 14.44 (S.D. 11.73) tears; average pain Disclosure statement: M.K.J. has received in the last 5 years score ¼ 5 (IQR 2–7) and 273 completed the retest. Reliability was honoraria for travel expenses, speaker fees and/or advisory commit- good: a ¼ 0.98; ICC (2,1) 0.98 (95% CI 0.97, 0.98). Linear weighted k tees from Lilly UK, Amgen, Servier, Merck, Medtronic, Internis and coefficients were mostly good (i.e. 0.61–0.77) for the activity items Consilient Health; and serves on the Scientific Committee of the (Q1–21), although one (Q17) was marginally lower at 0.58. Coefficients National Osteoporosis Society and International Osteoporosis for the symptom/self-image items (Q22–30) were generally lower and Foundation. D.P.A. has received consulting fees, speaking fees and/ mostly moderate, ranging from 0.50 to 0.66. DASH concurrent validity or honoraria from Amgen Spain and Bioiberica; and has received was strong: HAQ20 rs ¼ 0.91; SF36v2 Physical Function r ¼0.84; unrestricted research grants from Amgen Spain and Bioiberica. N.K.A. SF36v2 bodily pain r ¼0.71; hand pain rs ¼ 0.75; pain rs ¼ 0.70; has received honoraria from MSD, Roche, Novartis, Smith & Nephew, fatigue rs ¼ 0.64. The DASH discriminated between good, moderate Q-Med, Nicox, Servier, GSK, Schering-Plough, Pfizer and Rottapharm. and poor self-reported disease activity (P ¼ 0.001). The MDC95 DASH C.C. has received consulting fees, lecture fees and honoraria from score ¼ 9.26. There were no floor and ceiling effects. AMGEN, GSK, the Alliance for Better Bone Health, MSD, Eli Lilly, Conclusion: The British English version of the DASH required some Pfizer, Novartis, Servier, Medtronic and Roche. A.J. has held advisory modifications, but then was deemed appropriate by people with RA in board positions (which involved the receipt of fees) for Anthera the UK. It had good reliability and validity. A British English DASH is Pharmaceuticals and Servier; and has received consortium research available for the first time. Results were comparable to DASH studies grants from Roche. All other authors have declared no conflicts of in RA in other countries. Further research is needed to investigate the interest. unidimensionality and construct validity of the DASH using Rasch analysis. Disclosure statement: A.H. has received research funding from 173 TABLE 1. Meta-analysis of association between service models of care on Arthritis Research UK. All other authors have declared no conflicts of mortality and re-fracture interest. Orthogeriatrician Osteoporosis nurse specialist

173. CLINICAL EFFECTIVENESS OF SERVICE MODELS OF Hazard 95% CI Hazard 95% CI CARE FOLLOWING HIP FRACTURE: NATURAL ratio ratio EXPERIMENTAL STUDY Mortality (30 days) 0.73 0.65, 0.82 0.80 0.71, 0.91 1 1,2 1,2 Mortality (1 year) 0.81 0.75, 0.87 0.84 0.77, 0.93 Samuel J. Hawley , M. Kassim Javaid , Daniel Prieto-Alhambra , Second hip fracture (2 years) 0.95 0.79, 1.15 1.03 0.82, 1.31 Nigel K. Arden1,2, Janet Lippett3, Sally Sheard1, Cyrus Cooper1,2 and Andrew Judge1,2 1Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal 2 174. ANSWERING PROFESSOR BLACK’S CHALLENGE: HOW Sciences, University of Oxford, Oxford, MRC Lifecourse MANY RHEUMATOLOGY OUTPATIENTS ARE PARTICIPATING Epidemiology Unit, University of Southampton, Southampton and IN WORK? 3Elderly Care Unit, Royal Berkshire NHS Foundation Trust, Reading, UK Claire Holmes1, Jonathan Marks2, Adem Uner1, Cyrus Cooper3 and Karen Walker-Bone3 Background: Hip fractures entail severe clinical and public health 1Rheumatology, University Hospital Southampton NHS Foundation consequences. Service models targeting secondary fracture preven- Trust, Southampton, 2Rheumatology, Royal Bournemouth Hospital, tion at patients following a fragility fracture, as recommended by the Bournemouth and 3MRC Lifecourse Epidemiology Unit, University of Department of Health, may play a key role in curtailing future fracture Southampton, Southampton, UK rates. However, data on clinical effectiveness are scarce. We aim to evaluate orthogeriatric (OG) and nurse-led fracture liaison service (FLS) Background: Musculoskeletal disorders are one of the two major models of post-hip fracture care in terms of impact on mortality and causes of incapacity for work in the UK costing an estimated 0.5–2% rates of second hip fracture. gross domestic product. Historically, conditions such as RA were Methods: Data were obtained from the Hospital Episode Statistics associated with very poor workplace retention rates. At British Society database linked to Office for National Statistics mortality records for 11 for Rheumatology 2014, Professor Dame Carol Black challenged acute hospital trusts in a region of England. Our study population was rheumatologists to pay greater attention to the work status of our a cohort of patients admitted for a primary hip fracture from 2003 to patients. 2013. Interventions of interest, i.e. dates on which a hospital appointed Methods: During a 2-week period of July 2014, patients attending a an orthogeriatrician or setup/increased a FLS, were evaluated in terms large rheumatology service either as day cases or as outpatients were i118 Wednesday 29 April 2015 POSTER VIEWING II

surveyed about their current work status, their reasons for leaving 176. IMPACT OF HIP FRACTURE ON HOSPITAL CARE employment (where applicable) and advice received/given about work COSTS: A POPULATION BASED STUDY capacity by rheumatology staff, general practitioner (GPs), occupa- Jose Leal1, M. Kassim Javaid2,3, Daniel Prieto-Alhambra2,3, tional health services and/or employers. 2,3 2,3 2,3 Results: In total, 193 completed surveys were received. 137 (71%) Nigel K. Arden , Cyrus Cooper and Andrew Judge 1Health Economics Research Centre, Nuffield Department of were female and mean age was 53.7 years (range 16–87). 186 (96%) 2 had ever had a paid job but 80/193 (45%) were currently employed or Population Health, Oxford NIHR Musculoskeletal Biomedical self-employed, 4 were in full-time education and 7 were housewives/ Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford and carers. 54 (28%) reported that they had given up a paid job mainly or 3 partly because of their rheumatological condition. Among these, fewer MRC Lifecourse Epidemiology Unit, University of Southampton, than 50% reported that occupational health advice was available to Southampton, UK them; one-third reported that they had sought advice from their GP or hospital doctor about their work and 25% reported that their employer Background: Hip fracture is a major public health problem with the had taken advice about their work prior to them stopping. The majority majority of sufferers being old, female and vulnerable. Understanding of the younger workforce loss was attributable to inflammatory its costs is essential to aid decisions about improvements to health arthritis. Among those still in paid work, half reported that they had and social care services for these patients. However, limited data are been asked about their work in their clinic appointment but only one- available on the long-term costs of hip fracture in the UK. Our aim is to third were asked if they were having difficulty at work and fewer than estimate hospital costs of hip fracture up to two years post fracture for 25% had been offered advice about work. both index fracture and subsequent secondary hip fracture. We also Conclusion: We found that many rheumatology outpatients are no compare hospital costs before and after the index fracture. longer in paid work and a significant proportion of these blame their Methods: A cohort of patients with hip fracture were identified from arthritis. To take up Professor Black’s challenge, rheumatologists need the Hospital Episode Statistics (HES) database within a regional area to ask about work issues and be prepared to signpost workers to of England and followed until death or administrative censoring. All advice and support for their ongoing employment. HES records (inpatient stay, day cases, outpatient consultations, Disclosure statement: The authors have declared no conflicts of emergency attendances and critical care) between 2003 and 2013 interest. were extracted before and after index admission and valued using 2012/13 unit costs. Non-parametric censoring methods were used to adjust for censoring when estimating average annual costs and a 175. POTENTIAL NEW KEY PERFORMANCE INDICATORS IN generalized linear model was used to examine the main cost drivers. RHEUMATOLOGY Results: Between 1 April 2003 and 31 March 2013, 33152 patients were identified as having a hip fracture. Mean age was 83 (S.D. 8.2) R. Kapoor1 and Tanya Potter2 years and women accounted for 75% of the sample. Mean censor- 1Rheumatology, University Hospitals Birmingham, Birmingham and 2 adjusted 1-year hospital costs after index hip fracture were £14162 Rheumatology, University Hospitals Coventry and Warwickshire, (95% CI 14039, 14284), of which 97% (£13 749, 95% CI 13 627, 13 Coventry, UK 870) were due to admitted patient care. Acute hospitalization costs due to index fracture accounted for 61% (£8620; 95% CI 8569, 8671) Background: The only existing key performance indicator (KPI) in of total 1-year costs and no significant differences were found musculoskeletal disease are for hip fracture and recovery from fragility between index fracture and secondary hip fracture costs. Seventy- fracture. The British Society for Rheumatology (BSR) would welcome two per cent (£10 236) of post-hip fracture costs in the first year were the introduction of further musculoskeletal indicators that address the due to hospitalizations linked to the index fracture and the significant lack of commissioner incentives to deliver quality care for the cost drivers were institutionalization, death and second hip fracture. significant proportion of the population suffering from preventable For patients with hip fracture, mean annual costs increased by £10 741 and manageable rheumatic conditions. The BSR suggest that another compared with the year pre-event (P < 0.0001). In the second year indicator worthy of National Institute for Clinical Excellence (NICE) post fracture, the hospital costs were £3052 (95% CI 2945, 3158). consideration for RA or all inflammatory disease would be the Conclusion: Long-term hospital costs following hip fracture are high percentage of patients who have had an annual review which, as and mostly due to the first year after the index hip fracture. well as a DAS should include cardiovascular and osteoporosis risk Experiencing a second hip fracture after the index fracture accounted assessment (as outlined in existing NICE guidelines). for much of the increase in costs. The total annual hospital costs due Methods: Existing NICE guidelines state that people with RA should to hip fracture in the UK could reach £1 billion given the estimated 75 be offered an annual review to assess disease activity and damage 000 hip fractures per year. There is a strong economic incentive to and measure functional ability (using, for example, the HAQ); check for prioritize research funds towards identifying the best approaches to the development of comorbidities, such as hypertension, ischaemic prevent not only index but subsequent hip fractures. heart disease, osteoporosis and depression; assess symptoms that Disclosure statement: The authors have declared no conflicts of suggest complications, such as vasculitis and disease of the cervical interest. spine, lung or eyes; organize appropriate cross referral within the multidisciplinary team; and assess the need for referral for surgery and assess the effect the disease is having on a person’s life. We assessed 177. THE CLINICAL NEED FOR AN OUT-OF-HOURS current practice at University Hospitals Coventry and Warwickshire RHEUMATOLOGY REFERRAL SERVICE IN A UK TEACHING (UHCW) in line with the BSR proposed KPI. We reviewed the clinical HOSPITAL letters, blood results and radiology reports over a 14-month period (March 2013 to May 2014) of 10 patients with RA per each of the 8 Chai-Yiing Ling1 and Terence Gibson2 rheumatology consultants. 1Rheumatology Department, St George’s Hospital and Results: Over this 14-month period, 81.25% of patients had their 2Rheumatology Department, Guy’s and St Thomas’ Hospital, disease activity measured by a DAS for 28 joints, 0% had a HAQ score London, UK and 73.8% had their damage assessed. 52.5% of patients were checked for hypertension, 65% of patients had a lipid profile, 35% Background: Hospitals are faced with challenges of delivering an were assessed for osteoporosis and 5% assessed for depression. We integrated, high-quality, safe and value for money services. This assesses symptoms of vasculitis in 46.2% of patients and 91.25% of means that many specialist services are being reviewed in order to patients were referred to other members of the multidisciplinary team. achieve cost saving. Our rheumatology department in a single Quality of life was assessed in 55% of patients. teaching London hospital provides 24/7 services for the CTDs referral Conclusion: UHCW do not run a specific annual review clinic and this and general rheumatology services during working hours. Acute hot may be why some of these areas are not addressed fully. The clinic joints account for majority of rheumatology referral from the notes of these patients were not reviewed but if this is enforced as a emergency department (ED) out of hours. Delayed or inadequate new KPI then all information needs to be in the clinical letter as this is treatment of septic joints leads to joint damage. In the case of crystal the only information the GP receives. As beneficial as KPIs are, there is arthropathies, this may lead to unnecessary admission and prolong some overlap with this proposed BSR KPI and the GP Quality and hospital stays. As there is little information on whether a 24/7 service Outcomes Framework which also covers depression screening, required for general rheumatology, we did a prospective evaluation of assessment of bone health and cardiovascular risk. all acute hot joints admission via ED over 1-month period. Disclosure statement: The authors have declared no conflicts of Methods: All admissions to ED dated from 6 May to 4 June 2013 interest. were screened for presenting complaints of pain and swelling in POSTER VIEWING II Wednesday 29 April 2015 i119

non-prosthetics joints. The case notes, discharge summaries and the insight to their clinical care. It is our intention for this superior method ED CAS card were retrieved to examine the subsequent manage- to replace the current Patient 360 required every five years for ments, route of referral and discharge destinations. revalidation. Results: 72 patients presented to the ED with rheumatological Disclosure statement: The authors have declared no conflicts of complaints, but only 40 of them had acute hot joints. 45% of hot interest. joints cases presented during out of hours but only two cases had arthrocentesis in the ED. Causes of hot joints were: crystal arthropathies (27.5%), inflammatory arthropathies (12.5%), OA 179. AN ASSESSMENT OF METHOTREXATE-RELATED (15%), soft tissue pathologies (20%) and unspecified causes (25%). PATIENT KNOWLEDGE 75% of the cases were discharged home from the ED and the rest Puja Mehta1, Francesco Carlucci1, Charles Mackworth-Young2, were admitted to inpatients. Two patients who were admitted under Maresa Carulli1 and Dorian Haskard1 the orthopaedics underwent joint wash out which later transpired to be 1Rheumatology, Hammersmith Hospital and 2Rheumatology, crystal arthropathies. Five out of nine patients who were admitted had Charing Cross Hospital, London, UK crystal arthropathies. This could be diagnosed earlier with arthrocent- esis and potentially reduced the admission. Background: MTX is the most-widely prescribed DMARD for RA, used Conclusion: There was poor compliance with the trust guideline on as monotherapy or as an anchor with biologics. Adverse effects may hot joint management with only 5% of the cases undergoing lead to drug discontinuation and may include preventable, serious or arthrocentesis in the ED. 20% of admission of hot joints could be fatal incidents. Patient education is intrinsic to informed consent and avoided if patients had arthrocentesis and early diagnosis. It is not patient safety. A number of agencies have published guidelines cost-effective to have separate standalone 24/7 general rheumatology emphasizing MTX patient education, including the National Patient referral service. However, rheumatologists on 24/7 CTD roster could Safety Agency in the UK and the Institute for Safe Medication extend their coverage for acute hot joint referrals. Education and Practices in the United States. training for junior doctors, reinforcement of trust guideline and Methods: To assess patient knowledge, as defined by national emergency rheumatology clinic could reduce avoidable rheumatology standards presented in the Arthritis Research UK MTX patient admission and enhance the service provision. information leaflet. Questionnaires were distributed to 100 consecutive Disclosure statement: The authors have declared no conflicts of patients attending rheumatology clinics at two London teaching interest. hospitals in 2013. Results: 67% patients were female. The mean age was 46.7 years (range 18–82) and the mean duration of MTX therapy was 9 years 178. A TABLET A DAY KEEPS THE COMMISSIONERS AT BAY (range 0.3–25). In 19% of cases, English was not the first language. Bronwen Mackenzie-Green1, Russell Nightingale2, Roope Manhas1 16% thought that MTX was a steroid or a painkiller, 11% were and Stuart Kyle1 unaware of their prescribed dose. 36% stated that MTX was being 1Rheumatology Department, North Devon District Hospital, prescribed in both primary and secondary care and 14% were unsure Barnstaple and 23s Reporting Ltd, Taunton and Somerset NHS of who was responsible for blood monitoring. Of the 57% patients that Foundation Trust, Taunton, UK had a National Patient Safety Agency (NPSA) MTX monitoring booklet, only 21% stated that their doctor/nurse and 57% of their pharmacists Background: Transparency and evidence of quality care is increas- asked to see it. 9% of patients thought that folic acid was a painkiller ingly needed in the changing National Health Service (NHS). Clinical or an anti-inflammatory medication. 6% were taking folic acid on the commissioning groups demand that the work done is financially and same day as MTX and 4% were not taking any folic acid. 98% patients clinically effective with patient experience an important outcome were aware of the potential hepatotoxic effects, 84% of myelosup- measure. NHS reforms as set out in the King’s Fund highlight the need pressive effects and 83% of possible oral ulceration. Some patients for better measurement of health improvement on a daily basis. When attributed other adverse effects to MTX, including kidney failure (27%), a local patient support group donated a sum of money to our poor memory (9%), hypertension (9%) and diabetes (5%). Only 44% department in July 2014, the importance of putting this money towards patients knew that they should have annual influenza vaccination and lasting improvements in patient care seemed paramount. Tablet avoid live vaccines. 14% considered all vaccines to be contra- devices are being used in rheumatology departments to facilitate indicated. Most women were aware of pregnancy and breastfeeding data collection. Completing paper questionnaires and performing implications, but only 54% women and 49% of males were aware of scores are time-consuming and add to the paperwork burden. We recommendations for males regarding conception. have developed, in conjunction with 3s Reporting Ltd (an NHS owned Conclusion: Our results demonstrate deficiencies in patient knowl- innovation company), a web based survey software platform for edge of MTX and safety, despite all patients receiving doctor or nurse- patients and clinical teams. This will enable patients and staff to record delivered education prior to initiating treatment. Although the ques- data on any fixed or mobile device. tionnaire used was not validated, we had a 92% questions were Methods: The web based questionnaire provides secure patient completed and our findings highlight a need to improve current identifiable outcomes. Patients will be asked to complete standardized approaches to patient education, in order to improve patient safety. and validated questions of the Stanford HAQ and the Work and We have already implemented signed consent for blood monitoring. Productivity Activity Index (WPAI). Relevant patients groups are asked Strategies to aid recall and retention could include written information to fill in disease specific outcome measures. Rheumatoid patients are with multi-lingual translations, the development of multimedia educa- asked to complete a 28 joint count and a visual analogue scale (VAS). tional material, patient feedback on education received, testing patient PsA patients are asked to complete a 68/66 joint count and knowledge, targeted re-education and encouraging patients, primary Dermatology Quality of Life Index (DLQI) and patients with AS are care physicians and pharmacists to use the NPSA MTX monitoring asked to complete the Bath AS Disease Activity (BASDAI) score and booklet. Functional Index (BASFI) score. Outcome measures will be auto- Disclosure statement: The authors have declared no conflicts of matically calculated and available for use in the consultation. The interest. satisfaction questionnaire is modelled on the Commissioning for Quality in Rheumatoid Arthritis patient-reported experience measures, 180. DEVELOPING A NEW COMMISSIONING PATHWAY FOR to help standardize data collection. BIOLOGIC THERAPY IN RHEUMATOID ARTHRITIS Results: Data collection takes place in the outpatient waiting room; results are available for use during the consultation. Satisfaction data Jaita Mukherjee1, Lily Wong2 and Henry Penn1 are collected post consultation providing ongoing real time feedback 1Rheumatology, Northwick Park Hospital and 2Commissioning about patient experiences. Data will be available on a continually Support Unit, North West London NHS Trust, London, UK updated web based dashboard. Data analysis will enable patient experiences to be reviewed departmentally and by clinician/nurse Background: Managing RA with biologic therapy is mandated by between any chosen dates. clinical guidance issued by the National Institute for Clinical Excellence Conclusion: The use of tablets and this innovative secure web based (NICE). Where cases lie outside NICE criteria, individual funding survey system will facilitate accurate data capture on outcome requests (IFR) must be completed to support the use of a biologic measures and patient-reported experience measures. Access to agent identified by a named clinician. IFRs are for supposed to be these data will be invaluable for future commissioning discussions used in exceptional circumstances. These applications are onerous, and driving forward patient care. The survey can be adapted and and risk inequity of provision (despite safeguards to prevent this). Our developed by the user. We intend, with the British Society for department identified repeated requests were made for certain Rheumatology’s permission, to perform the Healthcare Quality indications outside NICE guidance. These are therefore not excep- Improvement Partnership audit using this system. Finally continual tional, and should be commissioned. Discussion with NW London patient experience data will provide clinical staff with more relevant commissioning support unit (CSU) revealed this was replicated across i120 Wednesday 29 April 2015 POSTER VIEWING II

NW London trusts. We wished to analyse IFR requests for RA to help primary/secondary care communication. This leads to better patient the CSU develop pathways for commissioning these drugs outside care and happier GPs. Taking into consideration both the quantitative NICE guidance. and qualitative results presented, the benefits of the GP advice line Methods: 67 IFRs for RA from North West (NW) London (excepting the outweigh the small time outlay required to run it. We hope that other Imperial Trust) were categorized according to indication. Applications departments considering developing similar electronic communication were divided according to agent requested, and previous DMARD use services find our experience useful. (including MTX, previous trial of TNF inhibitors or other biologic Disclosure statement: The authors have declared no conflicts of agents). 3 groups of patients were identified where applications were interest. received for similar indications. Following this review the CSU invited local clinicians from all rheumatology departments across NW London to attend a workshop to discuss the clinical evidence supporting cost 181 TABLE 1. Usage of email advice line over the first 2 years effectiveness of these groups of requests. This facilitated the First year Second year development of a new commissioning pathway for identifiable patient a cohorts requiring biologic therapy not fulfilling NICE criteria for funding. Total number of GPs 18 32 Total number of GP practices At least 9 At least 12 The outputs of the workshop were discussed at the NW London Number of queries from GPs 43 59 Clinical Commissioning Group (CCG) policy development group which Number of queries from other sourcesb 73 was attended by CCG general practitioner commissioners, lay Total number of patient queries 50 63 members and commissioning managers. aOf these 32 GPs, 12 had used the service the previous year and the other 20 were Results: Three groups of patients had IFR applications submitted for first time users. bThese all came from an intermediate care consultant the same indication. These requests were for the use of rituximab as a physiotherapist. GP: general practitioner. first-line agent in those with previous cancer, or interstitial lung disease, rituximab monotherapy for those with contraindications to MTX and biologic monotherapy. These form 67% of IFRs. A novel pathway for these indications was appended to the NICE pathway, and taken by the CSU to the NW London commissioning groups for 182. RHEUMDOC, A PHYSICIAN CHECKLIST TO RECORD approval. This was approved by the CCGs in autumn 2014. PATIENT STATUS AND LEVELS OF INFLAMMATION, DAMAGE Conclusion: IFRs are for exceptional circumstances. We demon- AND SYMPTOMS EXPLAINED BY NEITHER, AS strated the need for a pathway for biologic use outside NICE guidance, QUANTITATIVE SCIENTIFIC DATA RATHER THAN AS provided evidence and assisted commissioning additional pathways. NARRATIVE IMPRESSIONS Establishing this pathway for certain patient cohorts with RA will 1 2 1 improve access to biologic therapy and service delivery across North Isabel Castrejon , Elena Nikiphorou , Isabel Castrejon , Andra 2 1 West London. Developing a clear policy will reduce application F. Negoescu and Theodore Pincus 1 numbers presented to IFR panels, providing improved and standar- Rheumatology, Rush University Medical Center, Chicago, IL, USA dized treatment options for patients across the region. We have and 2Rheumatology, Addenbrooke’s Hospital, Cambridge, UK demonstrated how engaging with local clinicians, the CSU and CCGs can influence national policies. The challenge now is to unify policies Background: Physician global estimate (DOCGL) of patient clinical and services to provide patients optimum treatment opportunities. status is the most efficient RA core data set measure to Disclosure statement: The authors have declared no conflicts of distinguish active from control treatment in RA clinical trials. DOCGL interest. is directed to estimate the level of inflammation. However, clinicians may variably incorporate into DOCGL organ (joint) damage, as well as chronic symptoms unexplained by signs of inflammation or 181. COMMUNICATION BETWEEN PRIMARY AND damage, e.g. FM, in addition to inflammation. One approach to SECONDARY CARE IN RHEUMATOLOGY: SERVICE REVIEW clarify how DOCGL is estimated is for the physician to score 3 OF A GENERAL PRACTITIONER EMAIL ADVICE LINE AT THE additional 0–10 visual analogue scales (VAS) for inflammation, damage KELLGREN CENTRE FOR RHEUMATOLOGY, MANCHESTER and neither, as found on RHEUMDOC, a one-page physician checklist. ROYAL INFIRMARY We analysed RHEUMDOC in patients with different rheumatic diagnoses. Laura R. Newton1 and Rachel Gorodkin1 1 Methods: All patients seen at an academic rheumatology clinical Kellgren Centre for Rheumatology, Manchester Royal infirmary, setting have a RHEUMDOC checklist completed by a physician, which Manchester, UK includes four 0–10 VAS scores for overall status (DOCGL), inflamma- tion (DOCINF), damage (DOCDAM), and neither (DOCNON). Mean Background: In one of the regular meetings between the Kellgren scores were computed in patients in four diagnosis groups: RA, SLE, Centre for Rheumatology and the Central Manchester Clinical OA and FM. MANOVA was performed to compare the four groups, Commissioning Group (CCG) musculoskeletal leads, discussion adjusted for age, disease duration and education. Correlations of around good communication between primary and secondary care DOCGL with the three subscale scores were computed. identified an unmet need and the opportunity for service improvement. Results: Among 205 patients studied, 50 had RA, 66 had SLE, 57 had Methods: An email advice line was set up to provide general OA and 32 had FM. RHEUMDOC was completed in 5–15 s by the practitioner (GP) advice on queries around new rheumatology referrals, to be staffed by rheumatology consultants. Issues around confidenti- ality were discussed and permission was given at divisional level to proceed. The advice line went live on 19 October 19 2012. All emails 182 TABLE 1. Four physician estimates and Spearman correlations between the (including replies where available) were assessed by a single reviewer, DOCGL and the subscales by diagnostic category to document the following information: GP name, or other health care professional using the service; the nature of the query; the outcome of Variable, All patients RA SLE OA FM score range (n ¼ 205), (n ¼ 50), (n ¼ 66), (n ¼ 57), (n ¼ 32), the query; and any other feedback/comments. mean (S.D.) mean mean mean (S.D.) mean (S.D.) Results: Most of the queries were about new referrals (Table 1). There (S.D.) (S.D.) were often multiple questions about each patient, and common Physician global 3.9 (2.0) 3.9 (2.2) 2.9 (2.1) 4.5 (1.6) 4.9 (1.8) themes emerged: whether to refer the patient to rheumatology at all (DOCGL), 0–10 (50) or to another speciality (12); advised to refer to rheumatology (23), Inflammation 1.5 (1.8) 2.4 (2.4) 1.4 (1.6)* 1.0 (1.5)** 0.8 (1.2)** GP to manage (18), GP watchful wait after further treatment (DOCINF), 0–10 or investigations advised (12), to refer to another speciality (6), or Damage (DOCDAM), 2.8 (2.1) 2.6 (2.2) 1.8 (1.8) 4.4 (1.6)*** 1.9 (1.8) unknown (3); advice on how to manage the patient if not referred, or 0–10 until their OPA; and to confirm that an OPA had been generated Neither (DOCNON), 2.1 (3.0) 0.6 (1.9) 1.1 (2.3) 2.1 (3.1)* 5.4 (2.2)*** 0–10 or whether the patient needed to be seen more urgently (7). There was Correlations of physician global estimate (DOCGL) spontaneous positive feedback from at least half of the queries, and no with subscales and patient global negative feedback identified. The consultants running the service DOCINF 0.42*** 0.73*** 0.69*** -0.02 -0.05 found it easy to manage and not time-consuming. DOCDAM 0.57*** 0.38* 0.70*** 0.71*** 0.09 Conclusion: The Kellgren Centre currently provides 1500 new DOCNON 0.43*** 0.27 0.40* 0.43* 0.65* rheumatology appointments per year. In relation to this, the numbers PATGL 0.64*** 0.67*** 0.41** 0.57*** 0.19 going through the helpline are tiny, but the service provides an easy *P < 0.05, **P < 0.01 and ***P < 0.001 (using RA as the reference group). PATGL: point of contact for advice in borderline cases, and improved patient global estimate. POSTER VIEWING II Wednesday 29 April 2015 i121

rheumatologist. Mean DOCGL was highest in FM followed by OA Results: 340 patients with RA responded to the study [mean age: 62 (Table 1). The highest scores for DOCINF were seen in RA, DOCDAM years (S.D. 12.1) disease duration14.4 years (S.D. 11.7)]. Of these, in OA, DOCNON in FM. Significant correlations with overall DOCGL 73.8% were women and a third (32.3%) was employed. Just over half were seen for DOCINF in RA and SLE, DOCDAM in OA and SLE, and (55.9%) were on combination therapy, and 7.4% were on biologic with DOCNON in FM, OA, and SLE. DOCGL was correlated drugs. CFA failed to support the unidimensional structure of the 18 significantly with PATGL in RA, SLE and OA, but not FM (Table 1). item set of the MAP-Hand (chi-square 236.0 (degrees of freedom 120; Conclusion: Quantitative estimates of inflammation, damage and P < 0.001) indicating widespread local dependency. However, Mokken neither can be assessed in routine care. The data suggest face validity. scaling suggested that all 18 items showed a probabilistic ordering The expertise of the rheumatologist is not necessarily to recognize a with a moderate scaling level of 0.61 defined by Loevinger’s level of symptoms, but rather whether symptoms are explained by coefficient. Differential item functioning (DIF) was largely absent inflammation, damage, or neither, or 2 or 3 of these disease signs. across all contextual factors, but was present for gender for the Recording this information quantitatively may clarify clinical decisions. items tying shoelaces, opening screw top bottles and carrying heavy Disclosure statement: The authors have declared no conflicts of objects. At any level of hand function, men were more likely to score interest. higher (worse) than women for tying shoelaces, and women were more likely to score higher than men with opening screw top bottles. Reliability was high, but possibly inflated by local dependency. 183. QUANTITATIVE ASSESSMENT OF FATIGUE IN ROUTINE Consequently, four testlets were formed from the item set, resulting CARE USING A MULTIDIMENSIONAL HEALTH ASSESSMENT in much improved fit and unidimensionality. Nevertheless, some QUESTIONNAIRE gender DIF persisted. Some items favoured men and others women; Theodore Pincus1, Isabel Castrejon1, Annie Huang1, Andra the testlets were further merged in pairs where opposite bias existed. F. Negoescu2 and Elena Nikiphorou2 This resulted in perfect fit to the model, and no DIF. A significant 1Rheumatology, Rush University Medical Center, Chicago, IL, USA gradient of the transformed metric is seen across groups of functional and 2Rheumatology, Addenbrooke’s Hospital, Cambridge, UK limitation as defined by the HAQ (ANOVA F ¼ 217.1; P < 0.001). Women also showed more limitations in hand function than men (t- ¼ ¼ Background: Fatigue is an important problem for many patients with test; t 3.1; P 0.002). There was no significant difference by age ¼ ¼ rheumatic diseases, which generally is captured as a qualitative group (ANOVA F 0.254; P 0.851). MAP-HAND showed a high description rather than as quantitative data to compare from one visit Person Separation Index (PSI) reliability, even after adjustment for local to the next. Fatigue is included on a multidimensional HAQ (MDHAQ) dependency (PSI range 0.94–0.92). as a 0–10 visual analogue scale (VAS), permitting longitudinal Conclusion: Analysis of the Map-Hand questionnaire in a UK quantification. population of adults with RA satisfies Rasch model requirements Methods: All patients seen in one academic clinical setting complete after adjustment for local dependency. Thus the raw score is a an MDHAQ in 5–10 min in the waiting area prior to seeing the sufficient statistic for hand function, and an interval scale metric is rheumatologist in the infrastructure of usual care. The two-page available when required. Item bias cancels at the test level. MDHAQ includes physical function (FN) in 10 activities of daily living, Disclosure statement: The authors have declared no conflicts of three 0–10 VAS for pain (PN), patient global score (PATGL) and fatigue interest. (FT), a 60-symptom checklist, and demographic data. RAPID 3 (0–30) is the sum of three 0–10 scores for FN, PN and PATGL. Patients were classified into four groups: RA, SLE, OA, FM. Mean scores for fatigue 185. PATIENT-LED OPTIMIZATION OF FOLLOW UP: A and other MDHAQ scales were computed in the four diagnosis groups, PROPOSED MODEL and compared by MANOVA, adjusting for age, disease duration and James Ritchie1, Shoma Banerjee1, Lyn Williamson1 and education. David Collins1 Results: Analyses included 205 patients, 66 with SLE, 57 with OA, 50 1Rheumatology, Great Western Hospital, Swindon, UK with RA and 32 with FM. Mean fatigue scores were highest in FM, and differed significantly from RA, but did not differ significantly in RA, SLE Background: A common challenge in rheumatology is limited capacity and OA. Fatigue scores correlated significantly (r > 0.59, P < 0.01) with for scheduling urgent clinical reviews, on a background of routine scores for FN, PN and PATGL in all, RA and SLE patients, but at lower appointments that often fall during periods of stable disease. A levels in OA and FM, suggesting associations with diseases resultant drive to improve responsiveness of appointment scheduling characterized by higher levels of inflammation. to the needs of patients has led to trialling of Patient-Initiated Clinics Conclusion: Fatigue scores reflect other MDHAQ scores at high levels (PIC), where the scheduling of appointments is led by the patient and/ in RA and SLE, but at lesser levels in OA and FM. Fatigue can be or General Practitioner, with the aim of allowing the timing of collected in the infrastructure of routine care as quantitative data on an appointments to reflect the needs of patients. Randomized controlled MDHAQ, with no extra work for the doctor and minimal interference trial evidence has shown that patients with RA managed by PIC, when with clinic patient flow. compared with those managed traditionally, have over 30% fewer Disclosure statement: The authors have declared no conflicts of appointments and higher levels of satisfaction and confidence in their interest. care system, without significant differences in clinical or psychological wellbeing. Due to current pressures on our own outpatients depart- 184. PSYCHOMETRIC TESTING OF MEASURE OF ACTIVITY ment, we designed a questionnaire to gauge interest among our PERFORMANCE IN THE HAND (MAP-HAND) QUESTIONNAIRE patients in a proposed modified PIC system, Patient-led Optimization IN RHEUMATOID ARTHRITIS: RASCH ANALYSIS of Follow up (POF), designed to empower patients to take control and responsibility for their own care. Yeliz Prior1, Alan Tennant2, Alison Hammond1 and Sarah Tyson3 Methods: 100 patients with a diagnosis of inflammatory arthritis were 1Centre for Health Sciences Research, University of Salford, contacted and asked the following three questions: has there ever Manchester, UK, 2ICF Research Branch, Swiss Paraplegic Research, been a time when your disease was stable and you felt that moving Nottwil, Switzerland and 3Stroke & Vascular Research Centre, your appointment to a later date may have been more beneficial?, University of Manchester, Manchester, UK answer yes or no; if your disease was stable, how would you feel about a system that allowed you to notify us if you felt that your appointment Background: Originally developed in Norway, the Measure of Activity could/should be moved to a later date?; and if you had been seen in Performance in the Hand (MAP-HAND) is a self-reported questionnaire the last 6–8 months and, your disease was stable, would you find it including 18 items to assess using hands when doing everyday helpful to be offered the option of a telephone consultation in place of activities and is reported to be unidimensional. Our aim was to identify an appointment at the hospital? In response to questions 2 and 3 if the Map-Hand fits the Rasch model in a UK population of people with patients were given the following options: very undesirable; undesir- RA. able; don’t mind; desirable; and very desirable. Methods: Participants were recruited from 17 rheumatology clinics in Results: 48% of patients felt there had been a time when they the National Health Service. The internal construct validity (unidimen- would have preferred to move their appointment to a later date. 84% sionality) was assessed using confirmatory factor analysis (CFA); felt a system where they could delay their own appointment Mokken scaling; and the Rasch model (including the stochastic during periods of stable disease was either desirable (56%) or very ordering of items, unidimensionality and local independence). The desirable (28%). 82% felt the option of a telephone consultation during RUMM2030 software was used, utilizing the partial credit parameter- periods of stable disease was either desirable (46%) or very desirable ization of the Rasch model. (36%). i122 Wednesday 29 April 2015 POSTER VIEWING II

Conclusion: Patient-led Optimization of Follow up is a desirable 187. AUTOANTIBODY PROFILE AND ASSOCIATED CLINICAL model of care for over 80% of sampled patients with inflammatory OUTCOMES IN AN INDIAN POPULATION WITH MYOSITIS arthritis. Adequate engagement in such a system could help to ease Ashish J. Mathew1, Irene Francis2, John A. J. Prakash3, pressure on appointments and streamline scheduling. A proportion of 1 1 3 1 patients may prefer to remain under traditional follow up. Although Ruchika Goel , G Arvind , Shakti Laishram , Suvrat Arya , Nikhil Gupta1 and Debashish Danda1 consideration must be given to the impact of reduced frequency of 1 face-to-face consultations, evidence suggests patients suffer no Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, India, 2Brighton and Sussex Medical deterioration in clinical and psychological wellbeing. 3 Disclosure statement: The authors have declared no conflicts of School, Brighton, UK and Department of Clinical Microbiology, interest. Christian Medical College, Vellore, India Background: Association of myositis-specific (MSA) and myositis- associated (MAA) autoantibodies with clinical outcome is well known in idiopathic inflammatory myositis (IIM). Data on these autoantibodies MUSCLE DISORDERS in Indian patients are scarce. This retrospective study aims to establish the association between clinical disease manifestations and autoanti- body status in patients with IIM. Methods: Clinical data and autoantibody profile (SRP, Mi-2, Jo-1, 186. WHY DO PATIENTS WITH MYOSITIS DIE? A PL-7, PL-12, Ku, EJ, OJ, PM-75 and PM-100) of patients with IIM RETROSPECTIVE ANALYSIS OF A SINGLE CENTRE COHORT attending rheumatology clinics during the last 3 years were retrieved from hospital records. Univariate and regression analyses were Estefania Cogollo1, Marta A. Silva2 and David A. Isenberg3 performed to identify clinical associates of these antibodies, 1Internal Medicine, Hospital Principe de Asturias, Alcala de Henares, detected by line immunoblot assay (EUROIMMUN, Lu¨ beck, Spain, 2Internal Medicine, Hospital Distrital da Figueira da Foz, Germany). Figueira da Foz, Portugal and 3Centre for Rheumatology Research, Results: Of 131 patients (mean age 38.12 11.65 years; male:female University College London Hospital, London, UK ratio, 36:95), 117 had at least one MSA or MAA. These antibodies were mutually exclusive in 85 (73%) patients. Regression analysis revealed Background: Inflammatory myopathies (IM) are rare, affecting approxi- association of anti-Mi2 with arthritis (OR: 5; P ¼ 0.032), swallowing mately 8/100 000 people. Little is known about the causes of death in difficulty [odds ratio (OR) 4, P ¼ 0.04), neck and trunk muscle this condition. We have reviewed a carefully observed cohort of myositis involvement (OR 3 and 4.6; P ¼ 0.04 and 0.05, respectively). Anti-Mi2 patients followed up in a single centre for up to 30 years to assess the was protective for interstitial lung disease (ILD; OR 0.13, P ¼ 0.004). mortality rate, causes of death and predictors of poor prognosis. ILD occurred more commonly in the presence of anti-PL7 (OR 5, Methods: We have reviewed a database of patients who had met 3 or P ¼ 0.04). Anti-SRP and anti-PL12 were associated with presence 4 of the Bohan and Peter criteria for myositis, noting the age at onset, of fever (OR 3, P ¼ 0.04). Anti-Jo1 was independently associated ethnicity, sex, clinical features, serology, treatment and outcome. with mechanic’s hand (OR 5, P ¼ 0.02), while anti-PM75 was Results: 105 patients were assessed for the survival analysis (female associated with generalized oedema (P < 0.05). Autoantibody profile to male ratio of 2.9:1). 36.2% had adult-onset DM (ADM) 31.4% adult- did not differ in terms of frequency of Raynaud’s, skin and muscle onset PM (APM). In 6.7%, the onset was <18 years (juvenile myositis) involvement. and 25.7% had an overlap syndrome. The predominant ethnicity was Conclusion: Anti-PM75 and anti-SRP were the commonest Caucasian (64.8%) followed by Afro-Caribbean (21.9%), South Asian autoantibodies in this cohort. Presence of anti-PL7 and absence of (9.5%) and others (3.8%). Mean age at onset was 38.3 years. The Mi2 antibody were predictors of ILD. Association of Mi-2 with median follow up was 10 years (IQR 12). The course of the disease was musculoskeletal features and fever with SRP as well as PL12 were monophasic in 35.2%, relapse-remitting in 36.2% and chronic also noted. progressive (CP) in 28.5%. The observed 1 year survival was 100%. Disclosure statement: The authors have declared no conflicts of The estimated cumulative proportion survival at 5 and 10 years were interest. 93.8% and 83.8%, respectively. 24 patients died (22.9%), most of them were females (58.3%) and the majority had ADM (37.5%). The 188. WORKING TOWARDS STANDARDS OF CARE FOR main cause of death was infection, mostly pneumonia, followed by PATIENTS WITH MYOSITIS: RESULTS OF A SERVICE malignancy. Cardiac and pulmonary complications were also reported EVALUATION QUESTIONNAIRE causes of death (Table 1). Most patients who died (66.7%) had an initial creatine kinase level >10 times upper limit of normal and the James B. Lilleker1,2, Robert Cooper3,4, Patrick Gordon5, majority had a CP disease and had been treated with steroids plus two Janine Lamb6, Mark Roberts2 and Hector Chinoy1,4 immunosuppressive drugs. In univariate analysis, age (hazards ratio 1Centre for Musculoskeletal Research, University of Manchester, (HR) 1.036; 95% CI 1.007, 1.066; P ¼ 0.016), antisynthetase autoanti- Manchester, 2Department of Neurology, Salford Royal NHS body [hazard ratio (HR) 2.724; 95% CI 1.126, 6.590; P ¼ 0.026), cancer Foundation Trust, Salford, 3Department of Musculoskeletal Biology, (HR 2.791; 95% CI 1.082, 7.200; P ¼ 0.034) and involvement of only University of Liverpool, Liverpool, 4Department of Rheumatology, lower limbs (HR 7.963; 95% CI 1.016, 62.417; P ¼ 0.048) were Salford Royal NHS Foundation Trust, Salford, 5Department of associated with an increased risk of death. The involvement of both Rheumatology, King’s College Hospital NHS Foundation Trust, upper and lower limbs (limb þ/þ) was predictive of a better prognosis London and 6Centre for Integrated Genomic Medical Research, (HR 0.120; 95% CI 0.026, 0.560; P ¼ 0.007). When adjusted to age, University of Manchester, Manchester, UK limb þ/þ was the only factor statistically associated with survival, predicting a lower risk of death [HR 0.179 (95% CI 0.037, 0.862); Background: Idiopathic inflammatory myopathy (DM, PM and IBM) P ¼ 0.032]. negatively impacts the lives of around 10 000 UK sufferers. Care Conclusion: Despite the great improvement in survival rates observed provision by the National Health Service (NHS) is inconsistent and in patients with IM, mortality rates are higher than in the general hampered by a lack of guidance defining best practice. To date, only population. In our study infection and malignancy were the most the Arthritis and Musculoskeletal Alliance have defined standards of common causes of death, followed by cardiac and lung complications. care for patients with CTDs. No statement addressing specific needs Older age at onset, antisynthetase autoantibody, cancer and involve- of those with myositis exists. ment of only lower limbs were associated with an increased risk of Methods: A website-based questionnaire was produced by the death. Conversely, the involvement of both upper and lower limbs was authors (J.B.L., H.C.). Items surveyed were informed by outcomes of predictive of a better prognosis. a patient focus group at the Myositis UK annual meeting (July 2014) Disclosure statement: The authors have declared no conflicts of and included; pathway to diagnosis, care arrangements, treatments interest. offered and access to local services. A link to the questionnaire was

186 TABLE 1. Causes of death Lung Cardiac Malignancy Infection Other/uncertain Total Deaths, n (%) 2 (8.3) 4 (16.7) 6 (25) 7 (29.2) 5 (20.8) 24 (100) Specific cause, n Pulmonary Myocardial infarction, Hodgkin’s lymphoma, 2: Pneumonia, 5; Trauma, 1; GI bleeding, hypertension, 3; other, 1 gynaecological, 2; sepsis, 1; other, 1 1; others, 3 1; ILD, 1 lung, 1; other, 1 ILD: interstitial lung disease; GI: gastrointestinal. POSTER VIEWING II Wednesday 29 April 2015 i123

distributed by email to all members of Myositis UK with an email Results: Four hundred and ninety-eight patients with IIM were address on record (n 200). recorded as receiving immunosuppression, 240 with DM and 258 Results: 76 completed questionnaires were returned (response 38%). PM. Steroids were prescribed to 468/498 individuals with inflammatory Average age was 58 years and 70% were female. The proportion of myositis, with the initial oral prednisolone regimen >25 mg in 139 respondents with DM, PM and IBM was 36%, 28% and 36% subjects. Other immunosuppressive therapy was utilized in 301 (36%) respectively. Most respondents presented via their GP to a specialist of IIM patients, with the largest proportion being AZA (57.8%) and MTX (75%) with most waiting at least 1 month before referral (62%). The (33.9%). AZA was the most common first-line immunosuppressant rest either made direct appointments with a specialist or were treatment (57.1%), followed by MTX (34.2%) and MMF (3.3%). AZA admitted to hospital as an emergency. Respondents with DM were remained the most common first-line agent in every decade studied. most commonly initially referred to dermatology (46%), PM to Concerning second-line agents, MTX was most frequently selected rheumatology (62%) and IBM to neurology (56%). The median wait (32.1%) followed by AZA (24.4%) and MMF (23.1%). The commonest to diagnosis from point of first specialist review was 3 months (range third-line agent was MMF (35.3%). 0–84). 49% were given an incorrect diagnosis at some point. Conclusion: AZA was the most frequent immunomodulatory agent Rheumatologists oversee the care of most respondents with DM and utilized for myositis treatment in UK clinical practice. These data are in PM (64%, 90%). Most with IBM are cared for by neurologists (63%). contrast to the prescribing patterns in Europe and Australia, where Five (21%) with IBM indicated that they were not under specialist there is more frequent use of MTX as a first-line therapy. Two follow up. 34% felt at least satisfied with access to a myositis important limitations of this research need consideration: first, there is specialist nurse. None with IBM, and only 25% overall, felt at least a risk of misclassification bias, second, we are relying upon primary satisfied that psychological aspects of disease were adequately care records and medication prescribed through secondary care may managed. 94% with DM or PM had been offered steroids. Of those not be fully captured. receiving any treatment, 52% felt at least satisfied that they had Disclosure statement: The authors have declared no conflicts of received adequate side effect counselling and 17% with access to a interest. specialist pharmacist. Conclusion: Key unmet needs and variation in provision are high- lighted. In particular mis- and delayed diagnosis is common and low satisfaction reported with access to specialist nurses, pharmacists and regarding side-effect counselling and management of psycholo- ORTHOPAEDICS AND REHABILITATION gical aspects of disease. A high proportion of patients with IBM are not under active specialist follow up, potentially preventing participation in clinical trials. These results will inform the production of a standards of care statement specifically tailored to the needs of patients with 190. PREDICTORS OF FRAGILITY HUMERAL FRACTURES: myositis. By defining minimum expected standards of care we aim to AN OBSERVATIONAL STUDY help address these unmet needs and promote consistent good Maria H. Dobrzynska1, Alexander Oldroyd2 and Marwan Bukhari3 practice across the NHS. 1Medical School, Lancaster University and 2Deanery, North Western Disclosure statement: The authors have declared no conflicts of Deanery and 3Rheumatology, Royal Lancaster Infirmary, interest. Lancaster, UK

Background: Humerus fractures (HFs) are one of osteoporotic fragility 189. DISEASE-MODIFYING ANTIRHEUMATIC DRUGS fractures. This study aimed to determine the following unexplored OPTIONS FOR MYOSITIS IN UK CLINICAL PRACTICE areas: the predictors of HF by measuring BMD at different sites using a case-control approach; and the predictors of an isolated HF compared Cristina Parraga Prieto1, James Galloway1, Caroline Ming1, with multiple fractures. Hector Chinoy2 and Patrick Gordon1 Methods: A cohort of patients with humerus fractures attending for 1Rheumatology, King’s College Hospital, London and DXA between 2004 and 2011 were identified. The cohort was divided 2Musculoskeletal Research Centre, University of Manchester, into two groups: patients with isolated HF vs patients with multiple Manchester, UK fractures. Additionally, a control group which had no indication for scanning was age and sex matched with the HF cases. Patients’ Background: Idiopathic inflammatory myopathies (IIM) are long-term characteristics including age at scan, height, weight, body fat, index of inflammatory muscle disorders with significant morbidity and mortality. multiple deprivation (IMD) scores, BMD scores of the lumbar vertebrae Low incidence of the disease, heterogeneity of patients with this (L1–L4) and the femoral neck were compared between patients with condition and the scarcity of controlled trials make myositis a isolated HF vs multiple fractures and between cases and controls. challenging disease. Currently, there are no defined guidelines for Univariate and multivariate logistic regression models were applied to therapy and the best initial strategies for disease control remain identify variables predictive of HF in the case-control group and unclear. As part of a larger project studying inflammatory myopathies, variables predictive of isolated HF vs multiple fractures. Analyses were we performed an analysis to evaluate the patterns of immunosup- adjusted for possible confounders. pressant therapy use for IIM in the UK. Results: A total of 1566 patients were included in the study: 783 cases Methods: We identified all adults with a recorded diagnosis of IIM and 783 controls, inclusive of 684 (87%) females in each group. Cases within the Clinical Practice Research Database (CPRD) from 1 January included 447 patients with isolated HF (86% female) and 336 patients 1987 to 18 October 2013. CPRD collects data from general with multiple fractures (89% female). Results of univariate regression practitioners working with the primary care setting of the National analyses are shown in Table 1. In the case–control group, multivariate Health Service, used by around 20% UK practices. Participants with analysis adjusted for height, weight, body fat and deprivation score, other autoimmune diseases or conditions that might provide a revealed a significant association between having HF and lower BMD differential diagnosis for myositis were excluded. Demographic, in the lumbar spine odd ratio (OR) 0.03 (95% CI 0.01, 0.09) and the clinical and laboratory features of myositis and muscle biopsy, EMG femoral neck OR 0.01 (95% CI 0.002, 0.06). In the isolated vs multiple and therapeutic data were recorded on a baseline cohort of 836 fractures, multivariate-adjusted analysis showed a significant associa- patients with DM or PM. For each patient we analysed the longitudinal tion between age at scan and sustaining an isolated humerus fracture: prescribing data to identify first, second and third-line immunosup- lumbar spine OR 4.64 (95% CI 2.08, 10.36) and femoral neck OR 11.48 pressive agents. (95% CI 2.47, 53.34).

190 TABLE 1. Results of univariate regression analysis Characteristic Significance Cases with isolated HF Cases with multiple fractures Cases Controls Age at scan, years a,b 67.65 (10.94) 70.16 (11.27) 68.72 (11.14) 68.71 (11.14) Height, cm a 158.71 (8.93) 160.83 (8.21) 159.92 (8.58) 159.96 (8.12) Weight, kg 66.45 (13.85 69.52 (15.41) 68.20 (14.83) 68.71 (13.50) Body fat,% b 31.49 (7.57) 30.81 (8.15) 31.19 (7.84) 29.19 (7.92) IMD score b 18.79 (14.78) 18.14 (14.58) 18.51 (14.69) 16.99 (12.98) Lumbar spine (L1–L4) BMD, g/cm2 a,b 1.02 (0.20) 0.95 (0.19) 0.99 (0.19) 1.07 (0.19) Femoral neck BMD, g/cm2 a,b 0.85 (0.14) 0.79 (0.14) 0.83 (0.15) 0.90 (0.17) a b Data presented as mean (S.D.). Characteristic was significantly different between cases with isolated humerus fractures and cases with multiple fractures; characteristic was significantly different between cases and controls. HF: humerus fracture; IMD: index of multiple deprivation. i124 Wednesday 29 April 2015 POSTER VIEWING II

Conclusion: This study demonstrates that humerus fractures occur with performance in those with lower limb OA. However, after an individual higher body fat content, lower BMD and higher deprivation. Moreover, develops OA, it is uncertain whether their physical performance patients with multiple fractures were older and had lower BMD. Further declines at the same rate or more rapidly than those without OA. We work on differences between patients with fractures is needed. investigated this in the European Project on Osteoarthritis (EPOSA) Disclosure statement: The authors have declared no conflicts of which includes participants from Germany, Italy, Netherlands, Spain, interest. Sweden and UK. Methods: 2187 men and women underwent a baseline interview assessing demographic and lifestyle factors. Physical examinations 191. PREDICTORS OF BONE LOSS OVER TIME IN PATIENTS were conducted, and a diagnosis of clinical OA of the knee and hip WHO HAVE SUSTAINED FRAGILITY FRACTURES: AN based on the American College of Rheumatology criteria. Individuals OBSERVATIONAL STUDY were timed rising from a straight-backed chair five times consecutively Richa Sinha1 and Marwan Bukhari1 with their arms folded across their chests. The latter was repeated at 1Rheumatology, Royal Lancaster Infirmary, Lancaster, UK one year follow up to assess the degree of change. Results: The mean (S.D.) age of participants was 73.7 (5.0) years. The Background: Limited research has been done looking at bone loss over mean (S.D.) chair rise time increased from 12.85 (1.38) seconds to time. G. Jones et al. (1994) investigated bone loss over time in the elderly 13.36 (1.38) seconds during the study, a difference of 0.51 seconds. population and found that bone loss rate is higher in elderly patients. This change was significantly influenced by country with the greatest Patients who have been referred for more than one scan and for whom mean increase of 1.75 seconds in Italy and a reduction in mean time by data are present regarding their indication for scanning can give insight 0.64 seconds in Spain. After adjustment for baseline chair rise time, a into specific predictors. The aim of this observational study was to greater increase in this variable was found in those of female sex and investigate predictors of bone loss over time in the lumbar spine and greater age [b ¼ 0.66 (95% CI 0.33, 0.99) seconds and 0.05 (0.02, 0.08) femoral neck in patients who have sustained a fragility fracture. seconds respectively]. After similar adjustment, the presence of clinical Methods: Data from male and female patients who had sustained a knee or hip OA was associated with a greater increase in chair rise fragility fracture attending for more than one DXA assessment between time [b ¼ 1.28 (95% CI 0.84, 1.72) seconds and 0.85 (0.07, 1.64) 2004 and 2014 in the North West of England were used. The rate of seconds respectively]. Similar relationships were shown for self- bone loss over time was calculated in change in BMD per year. reported OA in the knee and hip, and the presence or absence of Univariate and a step wise multivariate linear regression models were knee pain, knee stiffness, hip pain and hip stiffness individually. With fitted included age, BMI, first BMD, steroid therapy, smoking, RA and the exception of clinical hip OA, these relationships were all maintained excess alcohol history as dependent variables. after adjustment for age, sex and country. Results: 3267 patients were included in the study. The mean age of Conclusion: Individuals with OA in either their knee or hip are likely to patients was 61.87 (interquartile range 54.8–69.62). 91% of the decline in physical performance more rapidly than their counterparts patients were female. 25% of the patients had sustained more than without OA. Clinicians should be aware of this increased propensity for one fracture. In the univariate analysis looking at bone loss rate in the deterioration in this group. Although disease progression may be an lumbar spine, first BMD, RA, smoking, steroid use and age were found important factor, the similar relationships shown for pain and stiffness to be statistically significant and therefore had a role in predicting bone alone suggest symptoms may also play a significant role. loss. However, in the multivariate analysis, the statistically significant Disclosure statement: C.C. has received honoraria from Servier; Eli (P < 0.05) predictors of bone loss over time were smoking, BMI, age Lilly; Merck; Amgen; Alliance; Novartis; Medtronic; GSK and Roche. All and first BMD. In the femoral neck, smoking, age and first BMD were other authors have declared no conflicts of interest. shown to be independently associated with bone loss over time. Table 1 shows the coefficients for both the univariate and multivariate analyses done on lumbar spine (L1–L4) and femoral neck (left). 193. NOVEL CLASSIFICATION OF KNEE OSTEOARTHRITIS Conclusion: In conclusion, the common predictors of bone loss over SEVERITY BASED ON SPATIOTEMPORAL ANALYSIS time in the lumbar spine and femoral neck are age, first BMD and Avi Elbaz1, Amit Mor1, Ganit Segal1, Ronen Debi2, Nachshon Shazar3 smoking. However, the effects of these predictors on the bone loss are and Amir Herman3 small although statistically significant. Further research is needed. 1AposTherapy Research Group, AposTherapy, Herzliya, 2Department Disclosure statement: The authors have declared no conflicts of of Orthopaedic Surgery, Barzilay Medical Centre, Ashkelon and interest. 3Department of Orthopaedic Surgery, Sheba Medical Centre, Tel Hashoner and Israel 191 TABLE 1. The coefficients for univariate and multivariate analyses looking at the predictors of bone loss Background: Knee OA is a common disease with estimated Predictor Univariate Multivariate Univariate Multivariate prevalence of 30% in patients over the age of 60. Classification coefficient coefficient coefficient coefficient systems have focused on radiology and clinical symptoms alone. The (lumbar spine) (lumbar (femoral (femoral gait changes in patients suffering from knee OA are well documented spine) neck) neck) in the literature and include, among other, lower step length and Smoker 0.0022 (P < 0.01) 0.0015 0.0030 (P ¼ 0.02) 0.0029 velocity. In this work we are suggesting a new classification method for Age 0.0003 (P < 0.01) 0.0003 0.0002 (P < 0.01) 0.0002 knee OA based on spatiotemporal gait analysis. First bone 0.0276 (P < 0.01) 0.0253 0.0174 (P < 0.01) 0.0198 Methods: Gait analysis of 2900 patients from AposTherapy dataset density BMI 0.1955 (P ¼ 0.59) 0.9021 1.6588 (P ¼ 0.17) (AposTherapy, Herzeliya, Israel) suffering from knee OA were included Steroid 0.0018 (P ¼ 0.01) 0.0015 (P ¼ 0.30) in the study. Men and women were analysed separately. The analysis Excess -0.0023 (P ¼ 0.08) 0.0008 (P ¼ 0.74) included three stages: clustering, classification and clinical validation. alcohol Clustering of gait analysis data by the k-means method created four RA 0.0028 (P ¼ 0.02) 0.0047 (P ¼ 0.07) groups. Two-thirds of the patients were used to create a simplified classification tree algorithm. The model’s accuracy was checked by using the remaining one-third of the patients. Clinical validation of the classification method was done by SF-36 and Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaires. OSTEOARTHRITIS: CLINICAL FEATURES Results: The clustering algorithm divided the data into four groups according to gait analysis severity. The classification tree algorithm used stride length and cadence as predicting variables for classifica- tion. The correct classification accuracy was 89.5% and 90.8% for 192. KNEE AND HIP OSTEOARTHRITIS ARE ASSOCIATED women and men, respectively. Clinical scores of the WOMAC and SF- WITH A FASTER DECLINE IN PHYSICAL PERFORMANCE AS 36 questionnaires correlated well according to severity group. For ASSESSED BY CHAIR RISES: RESULTS FROM THE example, in women, the rate of total knee replacement within a year EUROPEAN PROJECT ON OSTEOARTHRITIS after the gait analysis was 1.4%, 2.8%, 4.1% and 8.2% for knee OA grades 1–4, respectively. Mark H. Edwards1, Camille Parsons1, Avan Aihie Sayer1, Conclusion: Spatiotemporal gait analysis can be used to classify Cyrus Cooper1 and Elaine Dennison1 patients with knee OA according to disease severity. The most 1MRC Lifecourse Epidemiology Unit, University of Southampton, differentiating variables for classification are stride length and Southampton, UK cadence. Furthermore, gait analysis based on disease grading correlated with clinical data of pain, function and quality of life Background: OA is common in older adults and associated with Disclosure statement: The authors have declared no conflicts of disability. Cross-sectional studies have confirmed poorer physical interest. POSTER VIEWING II Wednesday 29 April 2015 i125

194. CALCIUM PYROPHOSPHATE DIHYDRATE CRYSTAL mechanism of reduced cartilage destruction by MSCs in arthritis. KNEE ARTHRITIS ARE CORRELATED WITH GENU VALGUM Proteoglycan loss is an indicator of early cartilage destruction. Aggrecan, WITH OSTEOARTHRITIS the main proteoglycan in human cartilage, can be cleaved by both matrix 1 1 1 metalloproteinases (MMPs) and a disintegrin and metalloproteinase with Masatala Nishikawa , Hajime Owaki , Shoichi Kaneshiro and a thrombospondin type 1 motif (ADAMTS) at different sites. ADAMTS (or Takeshi Fuji1 1 aggrecanase) cleaved aggrecan produces a NITEGE neoepitope and Department of Orthopaedic Surgery, Japan Community Health Care MMP-cleaved aggrecan produces a DIPEN neoepitope. Detection of Organization Osaka Hospital, Osaka City, Osaka, Japan these neoepitopes by antibodies can provide information about the major enzymes involved in aggrecan degradation in mouse cartilage and Background: CPPD is one of the common crystals that causes crystal has therefore set a target for the development of new drugs designed to induced arthritis. But the relation between CPPD crystal and OA inhibit cartilage destruction in RA. remains controversy. We investigated the relationship between CPPD Methods: In this study, the both neoepitopes were detected by crystal and OA of the knee. immunostaining in the cartilage of joints with AIA, using sections of Methods: One-hundred and forty-nine total knee arthroplasties were joints from mice used in Kehoe’s study. The severity of cartilage performed for grade III or IV OA of knees classified by Kellgren– damage was quantified by the presence of these stained neoepitopes Lawrence grading scale from September 2010 to May 2012. At the after injection of MSCs, compared with control (no MSCs). Different operation, joint fluids were collected from 143 knees (average age 74.8: timing of MSC administration was also tested (at day 3, 7, 14 and 28 male 19: female 124) and elucidated the CPPD crystal using polarizing after arthritis induction), to find which resulted in the least proteoglycan microscope. We evaluated the relationship between CPPD crystals, and loss. This was quantified by counting the percentage of cartilage cells age, BMI, CRP, ESR and matrix metalloproteinase-3 (MMP-3) at the surrounded by a NITEGE or DIPEN neoepitope-positive matrix. operation. We defined the degree of osteophyte formation as mild, Results: Results concluded that when normalized against the non- moderate and severe. We also defined the lower extremity alignment as arthritic control, DIPEN staining scored more highly than NITEGE varus [femorotibial angle (FTA) 1808), neutral (1708FTA<1808)and staining at day 3. With no MSC treatment, DIPEN staining scored more valgus (FTA<1708]. The relationship between CPPD crystals and highly than NITEGE staining at all time points, but scored less than osteophyte formation and lower extremity were also evaluated. non-arthritic controls at days 14 and 28. Furthermore, on average Results: CPPD crystals were detected from 46 OA knees (32.2%). DIPEN scored more highly than NITEGE for MSC-treated (þ15.8%), no There were no significant differences between CPPD(þ) and CPPD(–) MSC (þ13.1%) and controls (þ7.4%). groups for age, BMI, CRP, ESR and MMP-3. Although age, BMI, CRP, Conclusion: These results suggest that MMP degradation may be ESR and MMP-3 between CPPD(þ) and (–) were also evaluated more prominent than ADAMTS mediated degradation by day 3, separately in male and female, there were no significant differences. although a larger sample size would be needed to test whether this CPPD(þ) rate in female (35.5%: 44/124) was significantly higher difference is significant for later time points. (P ¼ 0.023) than that in male (10.5%: 2/19). CPPD(þ) rate were 63.6% Disclosure statement: S.S.P. has received research funding from (7/11) in severe osteophyte formed knees, 44.2% (19/43) in moderate INSPIRE. O.K. has received research funding from Oswestry osteophyte formed knees and 24.5% (20/89) in mild osteophyte Rheumatology. formed knees and there were significant differences (P ¼ 0.003). CPPD(þ) rate in valgus knees (61.5%, 8/13) was significantly higher than that in varus knees (31.5%, 35/111) (P ¼ 0.031). Conclusion: They are known that the population of knee OA is mainly female and CPPD arthritis has the possibility to cause incident OA. But OSTEOARTHRITIS: TREATMENT there was no report about gender influence about CPPD arthritis. If CPPD crystal is a byproduct or marker of OA, gender does not influence the CPPD(þ) rate as previously reported. In this study, we found the CPPD(þ) rates in female were significantly higher than that in 196. ILLNESS PERCEPTIONS PREDICT RESPONSE TO male. We also found high CPPD(þ) rate in severe osteophyte formed INTRA-ARTICULAR STEROID INJECTIONS IN KNEE knee. These results suggested that CPPD arthritis is the one possible OSTEOARTHRITIS pathogenesis of knee OA and makes it worse through severe 1,2 2 3 4 osteophyte formation. Genu valgum with OA are fewer than those George Hirsch , Terence O’Neill , George Kitas , Joan Duda and 3 with RA. However, in this study, we found high rate of genu valgum Rainer Klocke 1 with CPPD induced knee arthritis. Both RA and CPPD arthritis are Rheumatology, Dudley Group NHS Foundation Trust, Dudley, 2 inflammatory arthritis. Chronic inflammation induce by CPPD arthritis Institute of Inflammation and Repair, University of Manchester, 3 may be one of the factors that cause genu valgum with OA. Manchester, Rheumatology, Dudley Group NHS Foundation Trust, 4 Disclosure statement: The authors have declared no conflicts of Dudley and Institute of Sport and Exercise Sciences, University of interest. Birmingham, Birmingham, UK

Background: IA CS injections are widely used to treat pain in knee OA but predictors of response to treatment are poorly understood. Since psychosocial factors are known to influence outcomes in OA in OSTEOARTHRITIS: PATHOGENESIS general, we examined selected factors as potential predictors of treatment outcomes in this context. Methods: 141 subjects with painful knee OA underwent baseline assessment prior to injection of the knee joint. As well as physical and 195. INVESTIGATING THE CHONDROPROTECTIVE disease-related parameters, two groups of psychological character- POTENTIAL OF MESENCHYMAL STEM CELLS IN ARTHRITIS istics were assessed: firstly illness perceptions, assessed by the Revised Illness Perception Questionnaire (IPQ-R); and secondly pain Sweta S. Parida1 and Oksana Kehoe2 catastrophizing and depression, assessed by the Pain Catastrophizing 1Medical Student, Keele University Medical School, Keele and Scale (PCS) and depression subscale of the revised Arthritis Impact 2Rheumatology Research, School of Medicine and ISTM (Keele Assessment Scale (AIMS2), respectively. Symptoms were assessed University) at RJAH Orthopaedic Hospital, Oswestry, UK using the Western Ontario and McMaster Osteoarthritis Index pain subscale at baseline, 3 and 9 weeks, and response to treatment Background: Arthritis is a debilitating disease that reduces quality of life, defined as 40% reduction in baseline pain. Characteristics of affecting patients’ everyday living, their emotions and personal and responders and non-responders at each time point were compared. social relationships. It is therefore important to find therapies to combat Logistic regression models, adjusted for relevant disease-related the effects of this disease. Mesenchymal stem cells (MSCs) have anti- factors, were used to estimate effect size of predictors of response inflammatory and immunosuppressive properties and therefore have the with results expressed as odds ratio (OR) and 95% CI. potential to repair joint tissues that have been damaged in RA and OA. Results: Illness perceptions: responders at three weeks had higher The aim of this study was to investigate the effect of injecting MSCs scores for the IPQ-R domain treatment control (P ¼ 0.031) and lower intra-articularly in mice. Previous work showed that introducing MSCs scores for consequences (P < 0.005) than non-responders (see into the joints of mice with antigen-induced arthritis (AIA) resulted in less Table 1). Only treatment control was an independent predictor of cartilage destruction. Murine MSCs (mMSCs) were isolated from bone outcome in a logistic regression model [P ¼ 0.010, odds ratio (OR) marrow of mice and these mMSCs were injected into joints of mice with 1.21]. Responders at nine weeks had higher scores for treatment AIA. This caused reduced joint diameter swelling compared with controls control (P ¼ 0.002) and lower scores for both consequences of phosphate buffered saline (PBS) injections in the other knee of the (P < 0.001) and emotional representations (P < 0.012) than non- mouse. This study progresses from this work to investigate the responders. Consequences and treatment control contributed unique i126 Wednesday 29 April 2015 POSTER VIEWING II

196 TABLE 1. Logistic regression models of psychological predictors of response at 3 and 9 weeks Characteristic Week 3 Week 9

Baseline variable P-value OR 95% CI R2 P-value OR 95% CI R2 Consequences (IPQ-R) 0.105 0.93 0.86, 1.02 0.17 0.001 0.834 0.75, 0.93 30 Treatment control (IPQ-R) 0.010 1.21 1.04, 1.40 0.011 1.24 1.05, 1.47 Emotional representations (IPQ-R) — — — 0.847 0.99 0.90, 1.09

Depression (AIMS2) 0.065 0.98 0.95, 1.02 0.13 0.033 0.86 0.74, 0.99 0.20 Pain catastrophizing (PCS) 0.279 0.88 0.78, 1.01 0.143 0.97 0.94, 1.01

P-values displayed are for individual variables. Model P-values are displayed in the text. AIMS2: Impact Assessment Scale; IPQ-R: Illness Perception Questionnaire; OR: odds ratio. variance to a logistic regression model (P ¼ 0.001, OR 0.83 and Conclusion: We found no evidence that accurate injection of CS P < 0.011, OR 1.24, respectively). Depression and pain catastrophiz- results in superior outcome to inaccurate injection in knee OA nor any ing: responders had lower scores for depression and catastrophizing that physical factors including sonographic features of synovial at both three (P < 0.001 and P < 0.005, respectively) and nine weeks inflammation or radiographic severity influence outcome. (P < 0.001 and 0.001) than non-responders. Depression was an Disclosure statement: G.H. has unrestricted funding from the Dudley independent predictor of nine week outcome in logistic regression Group NHS Foundation Trust. All other authors have declared no (P ¼ 0.0.34, OR 0.86). conflicts of interest. Conclusion: This study suggests that illness perceptions, specifically beliefs in less serious consequences of illness and stronger beliefs of treatment effectiveness, predict improved and more prolonged 198. CARTILAGE TURNOVER AND INTRA-ARTICULAR response to CS injection in knee OA more so than lower levels of STEROID INJECTIONS IN KNEE OSTEOARTHRITIS depression. Since illness perceptions are modifiable, this may have 1 1 1 implications for patient education programmes. Kirsty Levasseur , George Hirsch , Jacqueline Smith , George D. Kitas1 and Rainer Klocke1 Disclosure statement: G.H. has unrestricted funding from the Dudley 1 Group NHS Foundation Trust. All other authors have declared no Rheumatology, Dudley Group NHS Foundation Trust, Dudley, UK conflicts of interest. Background: IA CS injections are commonly used interventions in patients with OA of the knee. Relatively little is known about how they work and what predicts response. C-telopeptide fragments of type II 197. ACCURATE INTRA-ARTICULAR INJECTION DOES NOT collagen (CTX-II) are created during articular cartilage breakdown and RESULT IN SUPERIOR PAIN REDUCTION FOLLOWING excreted in urine (uCTX-II). High-sensitivity CRP (hsCRP) in the serum CLINICALLY GUIDED INJECTION IN KNEE OSTEOARTHRITIS: has been linked to OA as a marker of its inflammatory component. We FINDINGS OF AN OBSERVATIONAL COHORT. examined the response of uCTX-II and hsCRP following IA CS injection in knee OA. George Hirsch1,2, Terence O’Neill2, George Kitas1, Aabha Sinha3 and Methods: 105 subjects (mean age 63.6, S.D. 11.3 years, 59.0% female) Rainer Klocke1 with knee OA underwent routine knee joint injection with 40 mg 1Rheumatology, Dudley Group NHS Foundation Trust, Dudley, 2 triamcinolone acetonide and lignocaine. HsCRP and uCTX-II were Institute of Inflammation and Repair, University of Manchester, measured at baseline and 3 weeks after IA injection with paired results Manchester and 3Radiology, Dudley Group NHS Foundation Trust, available for 67 patients (mean age 64.2, S.D. 10.8 years, 53.7% Dudley, UK female). UCTX-II was measured using the Urine Cartilaps enzyme immunoassay and corrected for simultaneously tested urinary creati- Background: IA CS injections are effective treatments for pain in knee nine (ng/mmol). HsCRP was measured using an enzyme immunoassay OA but responses to treatment vary. Uncertainty remains as to (mg/l). Radiographic severity of disease was evaluated using recent X- whether structural factors including accurate IA injection placement rays (anteroposterior, lateral and sky-line patellofemoral) to assess for influence outcome. In a pragmatic observational study, we aimed to features of OA including joint space narrowing (JSN; grade 0–3, i.e. determine whether accurate injection results in greater pain reduction absent to severe, with the highest grade at any compartment of the than inaccurate injection. knee joint used for analysis). Methods: 141 subjects with knee OA (mean age 63.4 years, 62% Results: Mean uCTX-II values 3 weeks post injection were lower when female) routinely referred for CS injection underwent assessment of compared with baseline: 325 (S.D. 205) ng/mmol and 405 (S.D. 243) ng/ personal and demographic factors, X-rays (anteroposterior, lateral and mmol, respectively; P < 0.001, paired t-test. In contrast, there was no sky-line patellofemoral) and US before aspiration and injection of the significant difference in mean hsCRP values before and after IA steroid joint, guided by clinical examination. US demonstration of an air- injection: 0 weeks 6.4 (S.D. 1.4) mg/l, 3 weeks 7.2 (S.D. 0.8) mg/l; arthrosonogram was used to determine whether injections had P ¼ 0.54. Both baseline uCTX-II values and the change in uCTX-II from entered the joint cavity. Pain severity at baseline and at three and baseline to 3 weeks post injection correlated with radiographic severity nine weeks post injection was assessed using the 500 mm Western of JSN; baseline median uCTX-II levels were 216, 350 and 563 ng/ Ontario and McMaster Osteoarthritis Index pain subscale. Mean mmol for grade 0/1, 2 and 3 JSN, respectively (P < 0.01, Kruskal– baseline pain was 271 (S.D. 96.7).Response to injection was defined as Wallis test); and median change in uCTX-II values were 8, 84 and 200 40% reduction in pain from baseline. Characteristics of responders ng/mmol for grade 0/1, 2 and 3 JSN, respectively (P < 0.01). There was and non-responders and mean change in pain for accurate (intra- no significant difference in the age, gender proportion, BMI or JSN articular) vs inaccurate (extra-articular) injections were compared using between the whole group and those in whom biochemical parameters univariate statistics with the aim of creating logistic regression models. were available. Inter-observer reliability of air-arthrosonogram assessment was Conclusion: Our study suggests that IA steroids in knee OA may exert calculated as mean k of 0.79 for agreement between three raters. part of their effect via reduction of cartilage breakdown. Subjects with Results: Eighty-three subjects (53%) were classified responders at more advanced radiographic disease are likely to have a larger three weeks and 56 (44%) at nine weeks. Ninety-eight subjects (70%) affected cartilage area and see the greatest reductions in uCTX-II. had a positive arthrosonogram. Accurate injection neither resulted in a Disclosure statement: The authors have declared no conflicts of higher rate of response to treatment than inaccurate injection (57.7% interest. vs 63.4%, P ¼ 0.355 at 3 weeks,39.3% vs 51.4% P 0.148 at 9 weeks) nor greater mean pain reduction (110.7 vs 116.9 mm visual analogue scale, P ¼ 0.781 at 3 weeks, and 65.2 vs 92.8, P ¼ 199. DEVELOPMENT OF AN ONLINE EXERCISE-BASED 0.247 at 9 weeks). There were no differences in mean measurements REHABILITATION PROGRAMME FOR PEOPLE WITH HIP AND of sonographic effusion and synovial hypertrophy, or scores for power KNEE OSTEOARTHRITIS Doppler signal and individual radiographic features of OA (joint space narrowing and osteophytes) between responders and non-responders Jennifer Pearson1, Nicola Walsh1, Sian Koskela2, Edith Anderson1 at three or nine weeks. However, those who had received previous and Michael Hurley2 injection were less likely to respond at nine weeks [P ¼ 0.026, OR 0.41 1Faculty of Health and Applied Sciences, University of the West of (95% CI 0.20, 0.86)] and responders at 9 weeks had lower mean England, Bristol and 2Faculty of Health, Social Care & Education, baseline pain score compared with non-responders (250 vs 288 mm, Kingston University and St George’s, University of London, P ¼ 0.031). London, UK POSTER VIEWING II Wednesday 29 April 2015 i127

Results: Thirty-nine studies were eligible and included in the review, Background: OA affects 8.5 million people in the UK. Access to comprising 3796 participants (1089 males; 2427 females). The quality healthcare professionals is limited due to increasing referrals and limited of the evidence-base was deemed moderate. There were superior resources, therefore other strategies are required to meet patient’s results in pain at 12 months (primary outcome), walking capability and needs. We are developing an online version of ESCAPE, an exercise and knee range of motion at each follow-up period for participants who self-management intervention to improve physical and psychological received greater than one to six physiotherapy contacts. There were wellbeing. Online programmes often produce unwanted, unusable, high- superior outcomes for Western Ontario and McMaster Osteoarthritis tech but low impact information with poor uptake, because they are Index (WOMAC; total) for participants who received greater than six developed without input from potential users. This study aimed to physiotherapy contacts when assessed in the first nine weeks, but this understand the user’s perspective on the role of the internet in the was not statistically different at 3 - to 6-month follow up. There was management of OA and their requirements for an online resource. This inconsistency in results for WOMAC function with no statistically approach should facilitate uptake and effectiveness of ESCAPE online. significant difference in results between up to six physiotherapy Methods: A survey of 200 people with lower limb and spinal OA was contacts and more at each follow-up period except the six to conducted to understand internet use and the role of technology as a 12-month assessment. Thirteen to 19 physiotherapy contacts were source of health care information. In addition, focus groups were more effective at 12 months than greater or lesser frequencies of conducted with participants who had experienced the intervention contact. face to face and those who were intervention naı¨ve to determine their Conclusion: This review suggests that the number of physiotherapy preferences for an internet resource. contacts to deliver exercise for people with knee OA does significantly Results: The survey response rate was 42%; 67% of respondents affect clinical outcomes and may have implications for current primary were female; mean age 67. 86% had used the internet. 99% of internet care service provisions. Further assessment is required to explore the users had used the internet at home; 27% of participants used the impact of number of physiotherapy contacts on exercise behaviours internet at work and 27% used the internet on the move. 77% of and adherence for people with knee OA. internet users had looked online for health-related information; 34% Disclosure statement: The authors have declared no conflicts of have watched someone else’s personal experience of a medical interest. condition; 24% have gone online to find others with same health condition; 23% have tracked their health symptoms online; and 20% have used an online resource to manage an existing health condition. 201. SELF-REPORTED SITTING TIME AND PHYSICAL Findings from the survey showed participant’s main concern about FUNCTION IN PATIENTS CONSULTING WITH PERIPHERAL using the internet centred upon privacy (cyber-crime) and finding JOINT PAIN relevant and trustworthy health information that was individualized to John G. Watkins1,2, Ebenezer K. Afolabi1, Krysia S. Dziedzic1 and their presentation. The focus groups participants wanted a simple and Emma L. Healey1 user-friendly website which provides personalized OA information and 1Research Institute for Primary Care & Health Sciences and 2School peer support. In order to trust the information the focus group of Medicine, Keele University, Keele, UK participants wanted it to be endorsed by a professional body, the National Health Service or healthcare professionals. However, there Background: A sedentary lifestyle has been linked to an increased risk were mixed opinions about whether the website should stand alone or of chronic disease and less favourable chronic disease outcome. be used as an adjunct to face-to-face care. Exercise is currently recommended as a key treatment in many chronic Conclusion: Many older people use the internet as a source of health conditions, including OA, however, limiting the amount of time spent information, but concerns regarding safe use and quality of information sitting may be just as important and a more achievable recommenda- exist. A website that personalizes information about OA would be tion for people with long-term conditions. The aim of this study was to welcomed by internet users who have joint pain associated with OA. investigate the association between self-reported sitting time and Disclosure statement: The authors have declared no conflicts of physical function in those consulting for peripheral joint pain within interest. primary care. Methods: Baseline data from the MOSAICS cluster trial (n ¼ 525), 200. HOW OFTEN SHOULD I SEE THE PHYSIOTHERAPIST? A which included patients aged 45 years and over consulting for SYSTEMATIC REVIEW AND META-ANALYSIS INVESTIGATING peripheral joint pain in 8 general practices (4 intervention, 4 control THE RELATIONSHIP BETWEEN NUMBER OF practices) in the North West Midlands, were drawn upon for the PHYSIOTHERAPY CONTACTS AND EFFICACY WHEN analysis. Self-reported participant characteristic such as age, gender TREATING OSTEOARTHRITIS OF THE KNEE and weight were collected. Participants were also asked to report the amount of time they spent sitting during the day and their physical Toby Smith1, Luke Pickup2, Linda Evans3, Sarah Latham4 and activity levels over the last 7 days (International Physical Activity Philip Conaghan5 Questionnaire, short form). Physical function was also assessed using 1Faculty of Medicine and Health sciences, University of East Anglia, 2 the Western Ontario and McMaster Osteoarthritis Index 8 physical Norwich, Rheumatology Research Group, School of Immunity & function subscale. Infection, University of Birmingham, Birmingham, 3Medical School, Results: The mean age of participants was 67.3 (S.D. 10.47) years, University of Leeds School of Medicine, Leeds, 4Physiotherapy 5 59.6% were female and mean weight was 80.14 (S.D. 16.27) kg. Department, St George’s Hospital, London and Institute of Median daily sitting time was 300 [interquartile range (IQR) 240, 420) Rheumatic and Musculoskeletal Medicine, University of Leeds & min and median physical activity was 1506 (IQR 462, 3832) mets per NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK min/week. Regression analysis demonstrated increased sitting time was significantly associated with reduced physical function (P ¼ 0.007) Background: OA is a major long-term condition, primarily manifesting in patients with peripheral joint pain independent of age, gender, as joint pain with functional impairment and consequent reduced weight and level of physical activity. participation and quality of life. Previous trials and meta-analyses have Conclusion: Increased self-reported sitting time was significantly demonstrated that exercise can significantly improve pain and function associated with a reduction in physical function. The results of this in OA of the knee. At present there is no consensus of which type of study may suggest that future guidelines should recommend that exercise is most effective and how, many physiotherapy contacts are patients with joint pain limit the amount of time they spend sitting. required to deliver maximal clinical improvements. The aim of this Further research is needed to determine if limiting sitting time alone is study was therefore to answer the question: does the number of as effective as participating in physical activity/exercise in terms of its physiotherapist consultations/contacts significantly affect the clinical impact upon physical function. As this was a cross-sectional analysis, outcome of exercise treatment for people with OA of the knee? causality is difficult to establish. In addition, as a self-report method Methods: A systematic review and meta-analysis of the published and was used, recall bias may have influenced the results, however recent unpublished literature was conducted. All clinical trials presenting research using an objective method to measure sedentary time clinical outcomes for a designated number of community or hospital demonstrated similar results. based physiotherapy contacts to deliver an exercise intervention were Funding: This paper presents independent research commissioned by included. The evidence was critically appraised using the Cochrane the NIHR Programme Grant (RP-PG-0407-10386). The views Risk of Bias tool. A random-effects meta-analysis was conducted by expressed in this paper are those of the author. assessing the standardized mean difference with 95% CIs of one to six Disclosure statement: J.G.W. has received an Academy of Medical contacts with intervals of higher contact numbers to deliver exercise Sciences INSPIRE student research grant. K.S.D. is part funded by the programmes. Published (AMED, CINAHL, EMBASE, psycINFO, NIHR Collaborations for Leadership in Applied Health Research and MEDLINE, Cochrane Library) and unpublished (OpenGrey, the WHO Care West Midlands. E.L.H. is part-funded by the NIHR Collaborations International Clinical Trials Registry Platform, Current Controlled Trials, for Leadership in Applied Health Research and Care West Midlands. UK National Research Register Archive) literature databases was The other author has declared no conflicts of interest. conducted on 1 April 2014. i128 Wednesday 29 April 2015 POSTER VIEWING II

Background: Osteoporosis is a serious public health issue with a major OSTEOPOROSIS AND METABOLIC BONE financial burden on health care systems worldwide. In the National Health Service, there are 300 000 fragility fractures per year which will DISEASE increase with improving life expectancy. Having one fracture doubles the risk of developing another fracture. With the national hip fracture database and the development of secondary fracture prevention services, there has been considerable improvement with improving 202. ZOLEDRONATE MONITORING AND ADVERSE EVENTS: bone health in hip fracture patients but not with vertebral fractures. RESULTS FROM TWO AUDIT CYCLES WITH IMPLICATIONS Osteoporotic vertebral fractures are common with one occurring every FOR PRACTICE 22 s in the over 50 s. Compared with hip fracture, vertebral fractures are Paul Arkell1, Parag Raval1, Vasileios Lostarakos1 and Zoe Paskins1 an important early indicator of osteoporosis. Despite being so common, 1Rheumatology, Haywood Rheumatology Centre, Burslem, UK a significant proportion does not come to clinical attention due to under- reporting and therefore inadequate treatment. Methods: To determine the extent of under-reporting locally, we Background: Zoledronate is an i.v. bisphosphonate licensed for the investigated how many vertebral fractures were not being reported in treatment of post-menopausal and steroid-induced osteoporosis. CT scans performed in our trust for other reasons. We examined the Recent Medicines and Healthcare products Regulatory Agency imaging of 103 consecutive CT scans performed at the trust and (MHRA) alerts have highlighted potential adverse events associated reviewed the reports. If a vertebral fracture was identified it was with infusions, including hypocalcaemia, and the need for appropriate graded. We then contacted general practitioner surgeries to determine monitoring. Guidance in the British National Formulary, recent MHRA if bone protection was prescribed. alerts and the National Osteoporosis Society guidance on vitamin D Results: From 103 CT scans there were 13 (12%) incidental vertebral testing have informed a local monitoring protocol whereby vitamin D fractures found with only 4 being mentioned in the initial reports and (Vit D), Magnesium (Mg), corrected calcium (Ca) and estimated none graded. The average age of patients with fracture was 74 years, glomerular filtration rate (eGFR) are measured within 8 weeks of and 62% were female. 62% of requests were for patients with infusion. This abstract reports results from a large single centre audit of malignancy. Others were for pulmonary embolism, abdominal pain, monitoring, safety data on adverse events and the results of a re-audit bloody diarrhoea, dyspnoea and lung fibrosis. 54% of fractures were completing the audit cycle. biconcave compared with wedge shaped. Thoracic vertebral fractures Methods: Zoledronate infusions occurring during periods September were predominant (69%), and in 3 patients fractures were found at 2010–August 2012 (cycle 1) and June–July 2014 (cycle 2) were multiple levels. On reviewing the imaging, 31% were grade 1, 54% identified from pharmacy dispensing records. Systematic retrospective grade 2 and 15% grade 3. We were able to obtain medication case-note review was undertaken for the first 100 and 50 unit numbers information from primary care for 9 patients. Only one patient was respectively. To assess the impact of changes between audits, groups commenced on cholecalciferol following their imaging and one was on were compared (number with appropriate timely monitoring bloods) Calcichew since 2011. Four patients were not on any bone protection using chi-square tests. Adverse event data were collected in cycle 1; and three were deceased. clinic letters, discharge summaries and other correspondence were Conclusion: Our results demonstrate a significant number of vertebral searched for reports of possible adverse events for the whole duration fractures are not being identified or reported. Even with limited of therapy. Where eGFR was <45, weight was used to calculate medication information it is clear these patients are not on bone Creatine Clearance (CrCl) using the Cockroft-Gault equation. protection, remaining at high risk of developing another fragility Results: In total, 144 patients with a diagnosis of osteoporosis were fracture. A vital step is having a standardized format of identifying included with median [interquartile range (IQR)] age 77 (69–83) and and reporting vertebral fractures. The International Osteoporosis 85% being female. Following the first audit, a standard operating Foundation has developed guidelines to aid this. Our radiology procedure was implemented and changes made to the process of colleagues are now encouraged to look for vertebral fractures on checking results pre-infusion. The percentage of timely monitoring routine CT imaging and clearly stating vertebral fracture when bloods is demonstrated in Table 1. All results had improved reporting. This is then highlighted to the requesting physician, which significantly in cycle 2. No patients received zoledronate with an facilitates accurate diagnosis and treatment of this neglected disease. eGFR of <35, in line with the summary product characteristics (SPC). Disclosure statement: The authors have declared no conflicts of However, one patient of low BMI had a CrCl of 29 ml/min. During 170 interest. patient-years of therapy there were 5 serious adverse events (AEs) including two suspected anterior uveitis, one acute kidney injury, one allergic reaction and one incidence of AF. Other commonly reported AEs were flu-like symptoms following first infusions (13), hypocalcae- 204. DIFFERENCES IN PAIN EXPERIENCE BETWEEN mia (6) and pyrophosphate arthropathy (2). WOMEN WITH AND WITHOUT OSTEOPOROTIC VERTEBRAL Conclusion: This audit shows that the implementation of a standard FRACTURES operating procedure for zoledronate use has been successful in Emma M. Clark1, Rachael Gooberman-Hill1 and Tim Peters1 optimizing adherence to monitoring guidelines. The frequency of AEs 1School of Clinical Sciences, University of Bristol, Bristol, UK is in line with national figures; however the potential seriousness of these underlines the need for timely and appropriate monitoring pre Background: Osteoporotic vertebral fractures (VFs) are present in and post treatment. However, the absence of a clear national standard 12% of older women, but fewer than a third come to clinical for monitoring has led to some confusion and regional variance in attention. One reason for this is lack of clear clinical triggers for referral practice over monitoring. Importantly, this audit demonstrates that for radiographs, including a lack of evidence about which character- eGFR may overestimate CrCl in elderly patients with low body weight istics of back pain may indicate the presence of a VF. We have shown and therefore formal calculation is recommended. that site of back pain can indicate the likelihood of VF, but what is not Disclosure statement: The authors have declared no conflicts of known is whether the quality or type of back pain in people with VFs is interest. different from those with back pain but no VFs. Methods: A comparative study was undertaken. Digital radiological 202 TABLE 1. Proportion of timely monitored bloods in cycles 1 and 2 archives were used to identify a population of potential participants Blood test Cycle 1 Cycle 2 P-value who had a thoracic radiograph for back pain. Inclusion criteria were Ca 82/100 43/44 0.003 aged over 60, female and thoracic spinal radiograph performed in the eGFR 85/100 43/44 0.003 previous 3 months. 683 potential participants were approached, and Mg 60/100 43/44 <0.001 all who agreed to take part self-completed a questionnaire assembled Vitamin D 34/100 31/44 <0.001 from domains and scales taken from questionnaires previously eGFR: estimated glomerular filtration rate. validated in UK populations including the McGill Pain Questionnaire and the Keele STarT back pain score as well as demographics. Cases were defined at the end of the study as those with a VF identified from 203. IDENTIFICATION AND REPORTING OF INCIDENTAL spinal radiographs by the PI using the ABQ method. Chi-squared tests VERTEBRAL FRACTURES FOUND IN NON-MUSCULOSKELETAL were used to assess univariable associations. COMPUTERIZED TOMOGRAPHY IMAGING Results: 65 cases and 135 controls completed questionnaires. Those with VFs were slightly older (77.9 years vs 73.2, P < 0.001), more likely Jasroop Chana1, Mahesh Kudari2, Sarah Yanny2 and to have previously fractured a bone (70.8% vs 42.5%, P ¼ 0.001) and Malgorzata Magliano1 more likely to have taken steroids (27.7% vs 10.4%, P ¼ 0.007). No 1Rheumatology and 2Radiology, Stoke Mandeville Hospital, difference was seen in severity of most recent episode of back pain Aylesbury, UK between cases and controls (mean visual analogue scale out of 10 for POSTER VIEWING II Wednesday 29 April 2015 i129

those with VFs 7.8 vs 7.7 in those without VFs). However, those with 206. TERIPARATIDE: AN UNEXPECTED ADJUNCT FOR THE VFs were more likely to describe their pain as brief, momentary or TREATMENT OF A LONGSTANDING INFECTED ELBOW transient (13.3% vs 4.9%, P ¼ 0.045), more likely to describe their back PROSTHESIS PREVENTED ARM AMPUTATION pain as crushing (12.3% vs 4.4%, P ¼ 0.041) but less likely to describe 1 1 1 their pain as taut (3.1% vs 11.8%, P ¼ 0.042). Furthermore, those with Maria Mouyis , Halina Fitzclarence , Michael Shipley , Jessica Manson1 and Coziana Ciurtin1 VFs were more likely to report that lying down improved their pain 1 (21.3% vs 13.4%, P ¼ 0.026) but that damp did not increase their pain Rheumatology Department, University College London Hospital, (29.6% vs 49.4%, P ¼ 0.029). Interestingly women with VFs were less London, UK likely to report pain spreading down their legs (22.2% vs 48.2%, P ¼ 0.001) and less likely to report neck pain too (55.4% vs 78.0%, Background: A 76 year old woman with known longstanding RA, P ¼ 0.002). several joint replacements, interstitial lung disease, osteoporosis and Conclusion: The results indicate that back pain in the presence of VF epilepsy presented to the general rheumatology clinic with left elbow has particular qualities that are different from those of back pain swelling, associated with severe pain, limited mobility, overlying skin without the presence of VF. Further work is needed to investigate cellulitis and leaking pus. The elbow X-rays were in keeping with whether these descriptions can be combined to produce a ques- severe soft tissue swelling and loosening of the left elbow prosthesis. tionnaire to discriminate between women with and without VFs. Despite being treated with teicoplanin and ciprofloxacin combination Disclosure statement: The authors have declared no conflicts of therapy, the lack of clinical response prompted the removal of the interest. elbow prosthesis. Due to lack of poor wound healing and ongoing evidence of infection, an above-elbow arm amputation was recom- mended by the orthopaedic surgeons. The patient refused this 205. CLUSTER ANALYSIS OF HIGH-RESOLUTION treatment option, and opted for long-term antibiotic therapy. PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY Methods: In the interim, she was commenced on teriparatide PARAMETERS IDENTIFIES BONE PHENOTYPES ASSOCIATED (recombinant parathyroid hormone) for the treatment of severe WITH HIGH RATES OF PREVALENT FRACTURE osteoporosis associated with vertebral fractures, specifically lumbar spine vertebrae 2 and 4. Her most recent DXA scan was in keeping Mark H. Edwards1, Danielle E. Robinson1, Camille Parsons1, Kate with a T score of 3.2 of the lumbar spine and 3.2 of the left hip. A. Ward2, Elaine M. Dennison1 and Cyrus Cooper1 Vitamin D and calcium levels were both normal as well as bone 1MRC Lifecourse Epidemiology Unit, University of Southampton, markers. Co-incidentally over the subsequent 8 months her elbow Southampton and 2Human Nutrition Research, Medical Research pain improved, the instability of the joint resolved and overlying soft Council, Cambridge, UK tissue inflammatory changes completely disappeared. The addition of teriparatide was the only change to her treatment. Long-term antibiotic Background: Osteoporosis is diagnosed clinically by areal BMD using therapy continued with the same agents. dual DXA, which is a two dimensional technique. Recent technological Results: Repeated X-rays showed complete resolution of the soft advances have allowed development of a three-dimensional assess- tissue swelling, callus formation and exuberant osteophytes and her ment of bone microstructure, density and strength—high-resolution bone markers were reported as normal. The treatment with antibiotics peripheral QCT (HRpQCT). Output from such scanners reports a was stopped with no recurrence of the elbow infection and patient’s wealth of information; here we report observations from the arm function remained reasonably preserved despite the elbow Hertfordshire Cohort Study that suggests that these data can be ankylosis in flexion. reduced to specific bone phenotypes that may be at greater risk of Conclusion: Previous case reports ascertained the efficacy of fracture. teriparatide in facilitating the osteointegration in aseptic prosthesis Methods: We studied 177 men and 159 women, aged 72.1–80.9 loosening and improving the outcome of spinal surgery. In our years, for whom HRpQCT (XtremeCT) images (voxel 82mm) acquired experience, this is the first case in the literature reporting teriparatide from the distal radius were available. Standard image analyses were efficacy in the treatment of septic arthritis, proven by the improvement performed for assessment of macrostructure, regional densitometry, of skin, subcutaneous tissue and bone healing process, in a patient cortical porosity and trabecular microarchitecture. The k-means who failed to respond to antibiotic therapy with poor prognosis due to partitioning method of cluster analysis was used with these HRpQCT associated comorbidities. variables to identify five clusters in men and five in women. Femoral Disclosure statement: The authors have declared no conflicts of neck areal BMD was also assessed by DXA (Lunar Prodigy Advanced). interest. Vertebral fracture assessments were completed using DXA and non- vertebral fractures status was obtained from participant interviews. Prevalent fracture rates and femoral neck areal BMD were determined 207. IS THERE A BONE-FORMING PHENOTYPE? for each cluster. OBSERVATIONS FROM THE HERTFORDSHIRE COHORT Results: Forty four (24.9%) men and 48 (30.2%) women had sustained STUDY fractures. Women with fractures were on average 1.7 years older and 1 1 1,2 3.1 years further from the menopause that women who had not Julien Paccou , Karen Jameson , Cyrus Cooper , 1,3 1 fractured (P < 0.05). Although analyses were carried out separately in Elaine M. Dennison and Mark H. Edwards 1 each sex, two morphologically similar, high-risk clusters were MRC Lifecourse Epidemiology Unit, University of Southampton, identified in both men and women. Cluster A contained 20 women Southampton, 2Nuffield Department of Orthopaedics, Rheumatology (50.0% fractured) and 14 men (35.7% fractured) and demonstrated a and Musculoskeletal Science, NIHR Musculoskeletal Biomedical bone phenotype with a mean trabecular density and trabecular Research Unit, University of Oxford, Oxford UK and 3Department of number both more than 1 S.D. below the sex-specific cohort mean. Rheumatology, Victoria University, Wellington, New Zealand Cluster B contained 26 women (50.0% fractured) and 30 men (50.0% fractured) and represented a bone phenotype with mean cortical Background: Positive associations between a radiographic diagnosis thickness and cortical volumetric BMD around 1S.D. below and, in of OA and areal (or two dimensional) BMD have been demonstrated men, mean total and trabecular area more than 1S.D. above, the sex- and appear strongest when bony features of OA are considered. Here specific cohort mean. Logistic regression showed fracture rates in we report associations between radiographic OA and a three- these clusters to be significantly higher than the lowest fracture risk dimensional assessment of bone density and strength, high-resolution cluster (cluster E; P < 0.05). The mean femoral neck areal BMD was peripheral QCT (HRpQCT). significantly lower than cluster E in women in clusters A and B Methods: A total of 318 participants (170 men and 148 women) from (P < 0.001 for both); in men, this was true in cluster A (P < 0.001) but the Hertfordshire Cohort Study, aged 71.5–80.5 years, underwent not cluster B (P ¼ 0.220). HRpQCT of the distal radius and tibia along with hip radiography. Conclusion: In this cross-sectional study, we have identified a cluster Differences in bone microarchitecture were assessed between those (B) that describes a bone phenotype that differs from the conventional with and without osteophytes, sclerosis or joint space narrowing (JSN) view of osteoporosis but is associated with a high proportion of in either hip. fractures. In men, this phenotype was not associated with lower areal Results: The mean (S.D.) age of participants was 75.5 (2.5) years; the 2 BMD measured by DXA and therefore could be missed using current mean BMI (S.D.) was 27.5 (4.1) kg/m . After adjustment for age and clinical assessments for osteoporosis. BMI, men with osteophytes had significantly higher trabecular Disclosure statement: C.C. has received honoraria from Servier; Eli volumetric BMD [Tb.vBMD, g/cm2; b ¼ 12.88 (1.76, 24.00), P ¼ 0.023] Lilly; Merck; Amgen; Alliance; Novartis; Medtronic; GSK and Roche. at the distal radius with a similar trend observed at the distal tibia All other author has declared no conflicts of interest. [b ¼ 10.97 (0.24, 22.19), P ¼ 0.055]. Men with osteophytes had i130 Wednesday 29 April 2015 POSTER VIEWING II

significantly higher trabecular thickness (Tb.Th, mm) at both skeletal 209. ASSESSMENT OF BONE GEOMETRY, VOLUMETRIC sites [b ¼ 3.24 (0.05, 6.42), P ¼ 0.046, distal radius; b ¼ 4.27 (1.07, BONE MINERAL DENSITY AND BONE MICROARCHITECTURE 7.46), P ¼ 0.009, distal tibia]. Men with sclerosis had significantly IN BOTH WOMEN AND MEN WITH DIABETES MELLITUS 2 higher cortical volumetric BMD [Ct.vBMD, g/cm ; b ¼ 29.17 (4.65, 1 1 1 53.69), P ¼ 0.020] and lower cortical porosity [Ct.Po,%; b ¼1.22 Julien Paccou , Mark H. Edwards , Karen Jameson , Elaine Dennison1,2 and Cyrus Cooper1,3 (2.24, 0.19), P ¼ 0.020] at the distal tibia after similar adjustment, 1 with a similar tendency for radial Ct.vBMD [b ¼ 13.58 (5.81, 32.97), MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK, 2Victoria University, Wellington, New Zealand and P ¼ 0.169]. Men with sclerosis also had significantly higher cortical 3 thickness [Ct.Th, mm; b ¼ 103.82 (3.11, 204.53), P ¼ 0.043] at the distal Nuffield Department of Orthopaedics, Rheumatology and tibia with an analogous tendency observed in the radius [b ¼ 66.69 Musculoskeletal Science, NIHR Musculoskeletal Biomedical (6.34, 139.71), P ¼ 0.073]. These differences were not replicated in Research Unit, University of Oxford, UK women. Interestingly, bone microarchitecture did not differ signifi- cantly in those with or without JSN in men or women. Background: High-resolution peripheral QCT (HRpQCT) captures Conclusion: We have demonstrated higher Tb.vBMD and Tb.Th in men novel aspects of bone geometry, volumetric BMD and offers the with osteophytosis and higher Ct.vBMD and Ct.Th, and lower Ct.Po in ability to measure bone microarchitecture, but data relating measures men with hip joint sclerosis. Our observations using this novel obtained from this technique in patients with diabetes mellitus are assessment of bone structure accord with previous research findings, inconsistent in women and lacking in men. and suggest that a bone-forming phenotype exists in men, if not women. Methods: Here we report an analysis from the Hertfordshire Cohort Disclosure statement: J.P. has received research funding from Study, where we were able to study associations between measures Servier and La Socie´ te´ Franc¸ aise de Rhumatologie. C.C. has received obtained from HRpQCT of distal radius and distal tibia in 350 consultancy fees and honoraria from Servier; Eli Lilly; Merck; Amgen; participants (184 men and 166 women) aged 71.5–80.5 years with or Alliance; Novartis; Medtronic; GSK and Roche. M.H.E. received a without diabetes mellitus; n ¼ 45 and n ¼ 305, respectively. Statistical fellowship grant from ARUK in order to carry out HRpQCT scans to analyses were performed separately for women and men. answer a number of questions. This research is funded by MRC Results: The mean (S.D.) age of participants was 75.6 (2.3) and 75.4 (Programme No U105960371). K.J. and E.M.D. have declared no (2.4) years in women and men, respectively. Participants with diabetes conflicts of interest. mellitus differed significantly in terms of weight whether for women (79.22 14.62 kg vs 70.21 12.26 kg; P ¼ 0.003) or men (89.16 11.30 kg vs 81.50 15.10 kg; P ¼ 0.003) but no differences were found regarding age, height, smoking status, alcohol intake, social class and physical activity among women or men. Analyses in women revealed that cortical porosity (Ct.Po,%) and cortical pore 208. ASSOCIATIONS BETWEEN STROKE, BONE QUALITY 3 AND FRACTURE: RESULTS FROM UK BIOBANK volume (Ct.Po.V, mm ) were higher in participants with diabetes mellitus [b ¼ 0.66 (0.01, 1.30), P ¼ 0.046 and b ¼ 3.80 (0.78, 6.83), Nicholas C. Harvey1,2, Julien Paccou1, Stefania D’Angelo1, P ¼ 0.014, respectively] at the distal radius. Adjustment for weight did Mark H. Edwards1, Cyrus Cooper1,3 and Steffen E. Petersen4 not materially affect the relationship described for Ct.Po.V [b ¼ 3.47 1MRC Lifecourse Epidemiology Unit, University of Southampton, (0.38, 6.56), P ¼ 0.028] but differences in Ct.Po were attenuated 2NIHR Southampton Nutrition Biomedical Research Centre, [b ¼ 0.65 (0.01, 1.31), P ¼ 0.053]. Analyses in men revealed that University of Southampton and University Hospital Southampton cortical porosity (Ct.Po,%) and cortical pore volume (Ct.Po.V, mm3) NHS Foundation Trust, Southampton, 3NIHR Musculoskeletal were higher in participants with diabetes mellitus [b ¼ 1.58 (0.40, 2.75), Biomedical Research Unit, University of Oxford, Oxford and 4NIHR P ¼ 0.009 and b ¼ 31.93 (13.08, 50.78), P ¼ 0.001, respectively] at the Cardiovascular Biomedical Research Unit, William Harvey Research distal tibia. Adjustment for weight did not materially affect the Institute, Queen Mary University of London, London, UK relationship described for Ct.Po.V [b ¼ 19.29 (1.54, 37.03), P ¼ 0.033] but differences in Ct.Po were attenuated [b ¼ 1.14 (0.044, 2.33), Background: We aimed to explore relationships between bone quality P ¼ 0.057]. Distal radial or tibial trabecular bone parameters analyses and risk of prior fracture and stroke. in participants according to their diabetes mellitus status revealed no Methods: UK Biobank is a large prospective cohort comprising 502 significant differences among men or women. 664 men and women aged 40–69 years, with detailed assessment at Conclusion: Our results confirm previous studies demonstrating baseline. Calcaneal quantitative US (QUS) indices [broadband US higher cortical porosity at the distal radius in women with diabetes attenuation (BUA) and speed of sound (SOS)] were measured mellitus and highlight similar abnormalities at the distal tibia in men. bilaterally, and the mean used in analyses. History of fracture, and This may confer a biomechanical disadvantage and explain the higher stroke diagnosed by physician, were self-reported. We used multi- fracture rate observed in diabetes mellitus patients despite normal or variable Poisson regression models with robust standard errors to higher areal BMD. investigate the cross-sectional relationships between QUS indices, Disclosure statement: J.P. has received grants from Servier and La and risk of prior fracture and stroke for men and women, controlling for Socie´ te´ Franc¸ aise de Rhumatologie. C.C. has received consultancy age, BMI, smoking, alcohol, educational level, physical activity, fees and honoraria from Servier, Eli Lilly, Merck, Amgen, Alliance, Townsend deprivation index, diabetes, systolic blood pressure and Novartis, Medtronic, GSK and Roche. All other authors have declared cholesterol lowering medications. no conflicts of interest. Results: Among 482 683 participants (median age of 58 years, 54.6% women), 7238 participants reported a previous stroke (1.5%). Both 210. FRAGILITY FRACTURE IDENTIFICATION WITHIN THE women and men in the highest quarter of the BUA had a lower risk of EMERGENCY DEPARTMENT previous stroke compared with those in the lowest quarter, which persisted after full adjustment for confounding factors [women risk Sarah Thompson1, Bappa Roy1 and Jane H. Gibson2 ratio (RR) 0.64 (95% CI 0.53, 0.76); men RR 0.80 (95% CI 0.69, 0.92)]. 1Emergency Department, Victoria Hospital and 2Fife Rheumatic Relationships with SOS were similar to those with BUA. Both women and Diseases Unit, Whyteman’s Brae Hospital, Kirkcaldy, UK men with a prior fracture were at higher risk of also reporting prior stroke, with the association stronger in women [women RR 1.41 (95% CI1.25, Background: Worldwide, a fragility fracture is estimated to occur 1.59); men RR 1.16 (95% CI 1.02, 1.32); P for sex interaction <0.001]. every 3 seconds, and the burden of fragility fractures on healthcare Conclusion: Calcaneal QUS indices are inversely associated with risk systems across the world is dramatically increasing. In Scotland, of previous stroke in both women and men; conversely a positive 39.6% and 52.4% of patients presenting with a hip fracture have had association between the risks of prior fracture and stroke appears suffered a previous fragility fracture. A first fragility fracture should stronger in women, with both sets of associations remaining robust therefore indicate the need for assessment of bone health yet only after full adjustment for confounding factors. Further prospective 32% of non-hip fracture patients and 67% of hip fracture patients studies are required to document the direction of causality. This receive an assessment of their fracture risk. An important first step in research has been conducted using the UK Biobank Resource. ensuring bone health assessment is therefore correct identification of Disclosure statement: C.C. has received consultancy fees and those patients who sustain a fragility fracture. Correct coding of honoraria from Servier, Eli Lilly, Merck, Amgen, Alliance, Novartis, fractures in the emergency department (ED) would allow fracture Medtronic, GSK and Roche. The other authors have declared no services and general practitioners to identify these patients. The aim of conflicts of interest. this project was to identify what percentage of fragility fractures are POSTER VIEWING II Wednesday 29 April 2015 i131

coded as such on the discharge letters produced by the ED. Secondly, 211 TABLE 1. Summary of BMC, areal BMD and BMAD Z-score and SDS results to identify reasons for incorrect coding on the discharge letter, Mean Number of patients by Z-score/SDS implement changes and re-audit after these interventions had been Z-score/SDS carried out. Z-score/ Z-score/ Z-score/ Z-score/ Methods: During a 1-week period in Sept 2013, all patients aged 50 SDS 0 SDS 0 to 1 SDS 1to2 SDS –2 years or over attending the ED were identified using the electronic BMC 0.57 5 7 3 2 patient management system. If the reason for attendance was an injury Areal BMD 1.31 2 5 6 4 then all investigations, letters and X-rays were reviewed to identify BMAD 0.99 3 6 5 3 fractures and their cause. The electronic discharge letter was reviewed BMC: bone mineral content for bone area; BMAD: bone mineral apparent density; to ascertain whether a fragility fracture had been correctly recorded. SDS: S.D. score. The grade of staff completing the discharge letter was also recorded. Interventions were instigated after the first audit to improve the rate of correct coding by staff. This included specific staff training sessions, 212. ‘YOU’RE PULLING MY LEG!’ TENSILE FORCES IN BONE reminder notices within the ED and by email and by altering the PRESERVATION AND ATYPICAL FEMORAL FRACTURES electronic discharge questions to improve understanding and com- Eliot D. R. Williams1 and Kenneth E. S. Poole2 pliance with full completion. A second audit was undertaken in one 1School of Clinical Medicine and 2Department of Medicine, week in April 2014. University of Cambridge, Cambridge, UK Results: There were 31 and 27 fragility fractures in audit 1 and 2 respectively of which 25.8% and 44% were correctly coded. Doctors Background: Thickening of the lateral femoral cortex has been asso- recorded 50% then 44.4% correctly and nurses recorded 5.8% then ciated with atypical subtrochanteric femoral fractures in patients taking 44.4% correctly after the interventions. bisphosphonates. We set out to create a normal range for thickness of Conclusion: Identification of and coding for fragility fractures are poor the medial and lateral femoral cortex in the subtrochanteric region of in the ED. Interventions to improve understanding and compliance with bisphosphonate naı¨ve individuals; to be used in future studies compar- completion improved nurse performance but not that of doctors. ing the same region in patients on long-term bisphosphonate therapy. Despite education and reminders, coding remained low at 44%. Methods: A convenience sample of 91 female volunteers (mean age Reliance on electronic searches for fragility fractures via ED systems 54 years; range 20–86 years) undergoing pelvic CT scans for other will fail to identify at least 55% of those who should have bone health reasons was taken. We set up a protocol to analyse the CT scans, assessment measuring the thickness (mm) of the medial and lateral cortex of the Disclosure statement: The authors have declared no conflicts of left femoral shaft inferior to the lesser trochanter. interest. Results: Increasing age was associated with thinner femoral shaft cortices in both the medial and lateral subtrochanteric cortex. 211. BONE MINERAL DENSITY FINDINGS IN PAEDIATRIC However, we found the rate of cortical loss after the age of 55 years PATIENTS WITH ANOREXIA NERVOSA was substantially greater in the medial cortex. There was statistically significant preservation of the thickness of the lateral cortex relative to Bhavisha Vasta1, Jacqueline Shipley2, Darren Hart2, Jackie Webb2 the medial cortex in patients aged over 55 years (P ¼ 0.001), with and Ashok Bhalla2 cortical thinning appearing to be 2.5 times less in the lateral aspect of 1Rheumatology, Worcestershire Royal Hospital, Worcester and the cortical shaft compared with the medial. 2Rheumatology, Royal National Hospital for Rheumatic Diseases, Conclusion: Studies of femoral shaft loading have shown that the Bath, UK medial cortex is subjected to large compressive forces whereas the lateral cortex is subjected to tensile forces of similar magnitude. This Background: BMD loss can be a serious consequence of anorexia suggests tensile forces may play a key role in bone preservation with nervosa (AN). Although controversial, DXA is sometimes requested in ageing. Interestingly, there is evidence that atypical femoral fractures AN patients aged under 18 years in the hope that knowledge of low develop from small transverse cortical fractures, within thickened BMD results will help motivate recovery. To date, the BMD distribution cortex, in areas of the shaft subjected to maximum tensile load. We in this group is unknown. In addition it is unclear whether measures hypothesize that failure of the lateral cortex to cope with high tensile such as bone mineral apparent density (BMAD) that are corrected for forces, in patients on long-term bisphosphonate therapy, is involved in bone size are preferential to areal BMD, which is used in adults. BMAD the pathophysiology of atypical femoral fractures. is considered a more accurate measure of BMD in a number of Disclosure statement: K.E.S.P. has received research grant funding paediatric conditions including cystic fibrosis and IBD. from Amgen and Lilly; and has received speaker fees from Amgen and Methods: Retrospective review was undertaken of case notes and Lilly. The other author has declared no conflicts of interest. BMD findings of all AN patients aged under 18 years referred to a tertiary UK centre for DXA between 2006 and 2013. DXA was performed using a Hologic QDR Discovery scanner. Hips are not included in the standard DXA scanning protocol in under 18 year olds ¨ and thus measures were derived for the lumbar spine only. The areal SJOGREN’S SYNDROME AND OTHER BMD (g/cm2) and corresponding Z-score, centiles for height for age, 2 CONNECTIVE TISSUE DISORDERS S.D. scores (SDS, equivalent to Z-scores) for bone area for height (cm ), bone mineral content for bone area (BMC, g) and BMAD (g/cm3) were calculated. Results: 17 AN patients aged under 18 years had DXA in the study 213. ELIGIBILITY FOR CLINICAL TRIALS IN PRIMARY period. All were female, with a mean age of 16.1 years, a mean BMI of SJO¨ GREN’S SYNDROME: LESSONS FROM THE UK PRIMARY 16.7, a mean age of menstruation of 13 years and a mean duration of SJO¨ GREN’S REGISTRY amenorrhoea of 12.4 months. None had sustained past fractures. Height for age (indicating bone length) appeared evenly distributed Clare Cartlidge1, Simon Bowman1, Wan-Fai Ng2, Katherine James3, within the 5–95% centile interval. The mean SDS for bone area by Bridget Griffiths4, Elizabeth Price5, Colin Prease6, Paul Emery6, height (indicating bone width) was also normal at 0.19. The mean areal James Andrews7, Peter Lanyon8, John Hunter9, Monica Gupta9, BMD was 0.841 g/cm2 and the mean BMAD was 0.224 g/cm3. BMC, Michelle Bombardieri10, Nurhan Sutcliffe11, Constantino Pitzalis11, areal BMD and BMAD Z-score and SDS results are summarized in John McLaren12, Anne Cooper13, Marian Regan14, Ian Giles15, Table 1. There was no statistically significant difference between the David A. Isenberg15, Vadivelu Saravanan16, David Coady17, mean areal BMD Z-score and mean BMAD SDS (P ¼ 0.4336). Applying Bhaskar Dasgupta18, Neil McHugh19 and Steven Young-Min20 International Society for Clinical Densitometry criteria of Z-score or 1Rheumatology, University Hospital Birmingham, Birmingham, SDS 2.0, 4 patients (24%) could be defined as having bone density 2Musculoskeletal Research Group, Institute of Cellular Medicine, below the expected range for age using areal BMD Z-scores and 3 3School of Computing Science, Newcastle University, 4Department patients (18%) using BMAD SDS. of Rheumatology, Freeman Hospital, Newcastle upon Tyne, Conclusion: Bone mineral content is reduced in female AN patients 5Department of Rheumatology, Great Western Hospital, Swindon, aged under 18 years. However, less than 25% have a bone density 6Department of Rheumatology, Chapel Allerton Hospital, below the expected range for age questioning the use of DXA in this 7Connective Tissue Diseases Group, Leeds Institute of Rheumatic group to help motivate recovery. As bone length and width are normal, and Musculoskeletal Medicine, Leeds, 8Department of size adjustment is not necessary and bone density can be assessed Rheumatology, University of Nottingham, Nottingham, with either an areal BMD or BMAD. 9Rheumatology, Gartneval Hospital, Glasgow, 10Centre for Disclosure statement: The authors have declared no conflicts of Experimental Medicine and Rheumatology, William Harvey Research interest. Institute, Queen Mary University of London and Barts’ Health, i132 Wednesday 29 April 2015 POSTER VIEWING II

11Rheumatology, St Barts, London, 12Rheumatology, Windygates, one or more comorbidities on domestic and outdoor activities Fife, 13Rheumatology, Royal Hampshire County Hospital, (P ¼ 0.036, P ¼ 0.042) and somatic and mental fatigue (P ¼ 0.033, Winchester, 14Rheumatology, Derby Hospital, Derby, P ¼ 0.008). Sicca symptoms, fatigue and pain were highly prominent 15Rheumatology, University College London, London, among interviewees. Similar to the quantitative findings, these symp- 16Rheumatology, Queen Elizabeth Hospital, Gateshead, toms were reported as affecting leisure and work participation. 17Rheumatology, Sunderland Royal Hospital, Sunderland, Conclusion: Although SS is not considered to impact adversely on 18Rheumatology, Southend Hospital, Southend, 19Rheumatology, people who have this disease, in this study, those with significant fatigue Royal National Hospital of Rheumatic Diseases, Bath and and comorbidity had higher disease activity levels and engaged 20Rheumatology, Queen Alexandra Hospital, Portsmouth, UK significantly less in work and leisure activities. This indicates a need for multidisciplinary interventions on self-management of fatigue and devel- Background: Our aim was to interrogate the UK Primary SS Registry opment of strategies to maintain involvement in work and leisure activities. (UKPSSR) in order to determine eligibility criteria for future studies, Disclosure statement: The authors have declared no conflicts of which give a sufficient level of severity to determine meaningful interest. improvement but do not prohibit recruitment to studies. Methods: We analysed data from 688 participants of the UKPSSR in 215. COGNITIVE IMPAIRMENT IN PRIMARY SJO¨ GREN’S terms of sex, age, disease duration, EULAR primary SS disease activity SYNDROME (ESSDAI) and patient indexes (ESSPRI) and components, unstimulated 1 1 2 3 salivary flow rates, anti-Ro/La antibodies and IgG and C4 levels. We then Katie L. Hackett , Dennis Lendrem , James Frith , Tim Rapley , 4 5 6 compared participant data with the eligibility criteria for the major three Vincent Deary , Katherine H. O. Deane , Simon Bowman , Julia 1 1 biologic studies in primary SS [the Trial of Remicade in primary Sjo¨ gren’s L. Newton and Wan-Fai Ng 1 2 syndrome (TRIPSS) study, the Tolerance and Efficacy of rituximab in Institute of Cellular Medicine, Institute of Ageing and Health, primary SS (TEARS) study and the Trial of anti-B-cell therapy in primary 3Institute of Health and Society, Newcastle University, 4Department SS (TRACTISS) study] and considered the effect of various ESSDAI of Psychology, Northumbria University, Newcastle upon Tyne, thresholds in likely trial design in the future. 5School of Health Sciences, University of East Anglia, Norwich and Results: The mean EULAR SS Disease Activity Index (ESSDAI) score 6Department of Rheumatology, University Hospitals Birmingham, was 4.82, the percentage with ESSDAI of 5 was 41.72%, of 7was Birmingham, UK 28.92%, of 9 was 17.29%, of 11 was 11.77% and of 14 was 5.09%. 71.47% of participants had ESSPRI dryness components of 5; 64.41% Background: Several small studies have investigated cognitive had a fatigue score of 5 and 51.47% had a pain score of 5. For future impairment in primary SS (PSS) using self-reported measures. We studies, an ESSPRI score of 5 and ESSDAI of 5 would allow 149 sought to quantify cognitive impairment symptoms in a large cohort of (21.37%) of database participants to be eligible. 307 (44.62%) 150 PSS patients compared with controls and to explore the participants would have been eligible for the TRIPSS study [354 if relationship between cognitive impairment with fatigue, pain and pilocarpine, MTX, AZA and MMF allowed (51.45%)], 201 (29.22%) for the mood symptoms. TEARS study and 185 (26.89%) for the TRACTISS study. Methods: PSS patients diagnosed according to the American Conclusion: The UKPSSR can be utilized for trial participation. Using European Consensus Criteria were recruited from 12 sites across the eligibility criteria of having an ESSDAI score of five or more, and UK. They were invited to complete the Cognitive Failures ESSPRI score of five or more allows for adequate participant Questionnaire (CFQ) as well as measures of mood (Hospital Anxiety recruitment while allowing for suitable disease severity. and Depression Scale), fatigue [visual analogue scale (VAS)], dryness Disclosure statement: The authors have declared no conflicts of (VAS) and pain (VAS). CFQ scores were compared with data from interest. controls. Completion of the CFQ yields a possible score between 0 and 100, with 0 demonstrating no cognitive symptoms. Results: 150 PSS patients and 198 controls completed the CFQ. An 214. THE IMPACT OF FATIGUE AND COMORBIDITIES ON independent samples t-test revealed a statistically significant DAILY ACTIVITIES IN PEOPLE WITH SJO¨ GREN’S SYNDROME (P < 0.001) increase in cognitive symptom burden in the patient Niamh Galavan1, Conleth Feighery2, Finbar O’Shea3 and group [mean score 43.7 (S.D. 17.8)] compared with controls [mean Deirdre Connolly1 score 35.9 (S.D. 12.9]. This difference persisted (P < 0.001) following 1Discipline of Occupational Therapy, Trinity Centre for Health analysis of covariance adjusting for age and gender. On average PSS Sciences 2Department of Immunology and 3Department of patients scored 8 points higher than controls on the CFQ. This is Rheumatology, St James’s Hospital, Dublin, Ireland comparable to data in other fatigued patient groups. There were significant correlations with pain, fatigue, anxiety, depression and Background: SS is defined as an autoimmune inflammatory disease subjective dryness scores with CFQ scores. In order to partition the affecting many different parts of the body, mainly tear and salivary variability in CFQ scores into its component parts, we performed a glands. Despite SS being recognized as the second most common multiple regression analysis. This confirmed that anxiety was the most autoimmune disease, there appears to be a dearth of interventions to important predictor of CFQ scores (P ¼ 0.004). address the needs of this client group. Although SS is rarely life Conclusion: Cognitive impairment is more common in PSS than the threatening, research has found that it impacts on various aspects of a general population and people with PSS are likely on average to score persons’ life. Additionally, fatigue remains an under-recognized 8 points higher on the CFQ. Anxiety is a predictor for cognitive failure in symptom. It is important to identify relationships between disease PSS. This work suggests that clinicians need to give consideration to activity, fatigue and activity participation levels in order to establish cognitive failure and anxiety in the management of PSS patients. intervention priorities. The purpose of this study therefore was to Disclosure statement: The authors have declared no conflicts of measure levels of fatigue in people with SS; identify factors that interest. increase fatigue and explore peoples’ perceptions of fatigue and how it impacts on their daily activities. 216. A QUALITATIVE EXPLORATION OF COPING WITH Methods: A mixed-method design was used. Participants were OCULAR SYMPTOMS IN PEOPLE WITH PRIMARY SJO¨ GREN’S recruited from a large teaching hospital. Those with anti-La and Anti- SYNDROME Rho antibody levels of 240.00 were invited to participate. Data were collected through self-report measures of disease activity [Profile of Rebecca J. Stack1, Sue Southworth1, Benjamin Fisher1, Fatigue and Discomfort – Sicca Symptoms Inventory (PROFAD-SSI)], Francesca Barone1, Joanne Daskin2, Jackie Cobb2, fatigue (Fatigue Severity Scale) and function (Frenchay Activity Christopher Buckley1, Saaeha Rauz1 and Simon Bowman3 Index).Participants were also invited to take part in an individual 1Centre for Translational Inflammation Research, University of interview. Quantitative results were analysed using SPSS while Birmingham, 2Inflammation Research Facility and 3Department of qualitative results were analysed using thematic analysis. Rheumatology, University Hospitals Birmingham NHS Foundation Results: Forty-six completed questionnaires were returned with 11 Trust, Birmingham, UK interviews completed. Over 75% of respondents scored a total greater than or equal to four on the FSS indicating significant fatigue. Fatigue Background: Primary SS (pSS) affects fluid secreting glands such as was significantly associated with low activity participation, particularly those producing tears, leading to dry and painful eyes, and frequently leisure/work and outdoor activities (P ¼ 0.001 and P ¼ 0.006). Significant the symptoms outweigh the clinical signs. The ongoing day to day differences were identified between those with and without significant management of pSS often involves many patient driven self-care fatigue in total disease activity scores (P ¼ 0.029), ocular sicca activities; however, the way that people cope with and manage the (P ¼ 0.023), vascular dysfunction (P ¼ 0.014), total activity participation impact of symptoms is poorly understood. Little is known about the (P ¼ 0.018) and outdoor activity scores (P ¼ 0.13). There were also range and impact of ocular symptoms that people with pSS face and significant differences between those with no comorbidity and those with how they cope with them. POSTER VIEWING II Wednesday 29 April 2015 i133

Methods: Fourteen people diagnosed with pSS were recruited from a APR30. Double-blind APR treatment continued to week 52; patients secondary care rheumatology clinic to participate in semi-structured could continue APR up to 4 additional years. qualitative interviews about coping with the early symptoms of pSS. Results: 504 randomized patients received 1 dose of study medication Interviews were audio-recorded, transcribed verbatim and analysed (placebo n ¼ 168; APR20 n ¼ 168; APR30 n ¼ 168). At week 52, modified using thematic analysis. ACR20 response was achieved by 63.0% and 54.6% of patients Results: Eye problems were described as a driver for seeking help continually treated with APR20 or APR30 from baseline, respectively. before diagnosis, and it was after diagnosis, that the link between eye Approximately 80% (285/344) of randomized patients completing Week problems and other symptoms, particularly dry mouth, was realized. 52 were still receiving APR at the data cutoff during their second year of People with pSS described a range of ocular symptoms including eye APR exposure. Patients receiving APR from baseline demonstrated pain, sensitivity to light and dryness which led to itching, redness, sustained improvements at Week 104 in modified ACR20/ACR50/ inflammation and scratching sensations. They also described how eye ACR70 response [61.3%/29.8%/16.0% (APR20) and 66.3%/35.6%/ symptoms would flare up and at times were very difficult to control. In 19.8% (APR30)]; median percentage change in SJC/TJC [88.9%/ some cases, the level of discomfort in the eyes was so severe it 80.5% (APR20) and 87.5%/76.7% (APR30)]; mean change in HAQ- prevented sleep, which had, in turn, an impact on general fatigue DI [0.33 (APR20) and 0.43 (APR30)]; mean change in DAS28 [CRP; levels. However, people with pSS made the distinction between the 1.61 mg/l (APR20) and 1.83 mg/l (APR30)]; achievement of DAS28 fatigue that they felt throughout their body, and the fatigue that (CRP) <2.6 mg/l [35.1% (APR20) and 38.6% (APR30)]; and PASI-50/ affected their eyes. For some, eye fatigue was pervasive and daily PASI-75 response [53.7%/36.6% (APR20) and 54.7%/30.2% (APR30)]. activities involving the eyes such as reading, using the computer and No new safety concerns were observed with treatment through week driving were impaired. A number of practical coping mechanisms to 104. During weeks >52 to 104, adverse events (AEs) occurring in 5% self-manage eye symptoms including creating humid environments to of APR-exposed patients were nasopharyngitis and upper respiratory sleep in, finding time to rest their eyes and identifying appropriate eye tract infection; most AEs were mild/moderate in severity with no long- drops or replacement tears were described, but it was accepted that term increase in AE incidence and severity. Diarrhoea and nausea some symptoms were impossible to control. Eye discomfort that was occurred at lower rates in weeks >52 to 104 (1.7% and 1.2%, difficult to alleviate appeared to be associated with feeling anxious and respectively) than in weeks 0 to 52 (15.3% and 12.4%, respectively). irritated. Some people struggled to cope with the limitations on their Serious AEs occurred in 6.4% (APR20) and 4.7% (APR30) over weeks vision, eye pain and fatigue that pSS causes. >52 to 104. Fewer discontinuations due to AEs occurred during weeks Conclusion: People with pSS experience a range of ocular symptoms >52 to 104 (1.5%) than weeks 0 to 52 (8.2%). which impact daily functioning, sleep and wellbeing. While many Conclusion: Over 104 weeks, APR demonstrated sustained clinically people develop adaptive strategies to manage their eye discomfort, meaningful improvements in signs and symptoms of PsA, physical some struggle to cope with the range of eye symptoms described. function, and associated psoriasis. APR continued to demonstrate an Ocular symptoms present a number of self-management challenges acceptable safety profile and was generally well tolerated. for people with pSS and for some additional support is needed to Disclosure statement: D.D.G. has received consulting fees from manage on going psychological distress and anxiety related to eye AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Pfizer, Novartis symptoms. and UCBB; and has received research grants from AbbVie, Amgen, Disclosure statement: The authors have declared no conflicts of BMS, Celgene Corporation, Janssen, Pfizer, Novartis and UCB. A.K. has interest. provided expert advice to and/or received research grants from Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche and UCB. P.J.M. has received consulting fees from Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, SPONDYLOARTHROPATHIES UCB, Celgene Co., Novartis and Roche; has served on speakers’ bureaus on behalf of Abbott, Amgen, Biogen Idec, BMS, Genentech, (INCLUDING PSORIATIC ARTHRITIS) Janssen, Eli Lilly, Pfizer and UCB; and has received research grants from Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, Celgene Co., Novartis and Roche. J.J.G.-R. has received research grants from Roche and Schering-Plough; is on the advisory boards of 217. LONG-TERM (104-WEEK) EFFICACY AND SAFETY BMS, Pfizer, Roche, Schering-Plough and UCB SA; and has received PROFILE OF APREMILAST, AN ORAL PHOSPHODIESTERASE lecture fees from BMS, Roche, Schering-Plough and Wyeth. S.H. has 4 INHIBITOR, IN PATIENTS WITH PSORIATIC ARTHRITIS: received research grants and/or consultant fees Celgene Corporation, RESULTS FROM A PHASE III, RANDOMIZED, CONTROLLED Pfizer, UCB, BMS, GSK, Roche, Janssen, Novartis and Merck; and has TRIAL AND OPEN-LABEL EXTENSION (PALACE 1) served on speakers’ bureaus on behalf of Celgene Corporation, Pfizer, Adewale O. Adebajo1, Dafna D. Gladman2, Arthur Kavanaugh3, Philip UCB, BMS, GSK, Roche, Janssen, Novartis and Merck. E.L. has J. Mease4, Juan J. Gomez-Reino5, Stephen Hall6, received research grants from Amgen, Eli Lilly, Novartis and Servier; and Eric Lespessailles7, Georg Schett8, Kamal Shah9, ChiaChi Hu10 and has served on speakers’ bureaus on behalf of Amgen, Eli Lilly, Novartis 11 and Servier. G.S. has received consulting fees from Abbott, Celgene Ju¨ rgen Wollenhaupt 1Department of Rheumatology, University of Sheffield, Sheffield, UK, Corporation, Roche and UCB; and has received research grants from 2Division of Health Care & Outcomes Research, Toronto Western Abbott, Celgene Corporation, Roche and UCB. K.S. is an employee of 3 Celgene. C.H. is an employee of Celgene. J.W. has received research Hospital, Toronto, ON, Canada, Division of Rheumatology, grants and consulting fees from Abbott, BMS, MSD, Pfizer and UCB. and Immunology Department of Medicine, University of California, The other author has declared no conflicts of interest. San Diego, CA, 4Department of Rheumatology, Swedish Medical Centre and University of Washington School of Medicine, Seattle, WA, USA, 5Department of Rheumatology, Hospital Clinico 6 218. ETHNIC DIFFERENCES IN THE RESPONSE TO ANTI- Universitario, Santiago, Spain, Department of Rheumatology, TNF IN PATIENTS WITH ANKYLOSING SPONDYLITIS Monash University, Melbourne, Australia, 7Department of Rheumatology, University of Orle´ ans, Orle´ ans, France, 8Department Rebecca Adshead1, Hasan Tahir1, Judith Bubbear1, of Rheumatology, University of Erlangen-Nuremberg, Erlangen, Simon Donnelly1 and Iggy Chau1 Germany, 9Global Drug Safety & Risk Management, Celgene 1Rheumatology, Whipps Cross Hospital, London, UK Corporation, 10Statistics, Celgene Corporation, Warren, NJ, USA and 11Department of Rheumatology, Scho¨ n Klinik Hamburg Eilbek, Klinik Background: In 2010 we set up an Early Inflammatory Back Pain fu¨ r Rheumatologie, Hamburg, Germany (EIBP) service in an ethnically diverse area in east London to screen patients with inflammatory back pain (IBP). The service provides an Background: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, efficient pathway to facilitate early diagnosis of axial spondyloarthro- helps regulate immune responses in PsA. PALACE 1 compared the pathy with prompt access to treatment and educational support. Data efficacy/safety of APR with placebo in patients with active PsA despite have been published to suggest that ethnicity and cultural differences prior conventional DMARDs and/or biologics. We report the efficacy/ may influence disease activity in patients with AS; however, very few safety of APR treatment over 104 weeks. studies have investigated differences in anti-TNF response between Methods: Patients were randomized (1:1:1) to placebo, APR 20 mg b.i.d. diverse ethnic groups. No ethnicity related pharmacokinetic differ- (APR20), or APR 30 mg b.i.d. (APR30) stratified by baseline DMARD use ences have been observed between Caucasians and Asians with (yes/no). Patients whose swollen/tender joint counts (SJC/TJC) had not golimumab. The aim of this study was to establish whether a difference improved 20% at week 16 were considered non-responders and were in response to anti-TNF exists between ethnic groups. required to be re-randomized (1:1) to APR20 or APR30 if initially Methods: A retrospective study was performed on all AS patients randomized to placebo, or continued on their initial APR dose. At week taking anti-TNF attending the specialist EIBP service. All patients had 24, all remaining placebo patients were re-randomized (1:1) to APR20 or fulfilled National Institute for Clinical Excellence criteria before i134 Wednesday 29 April 2015 POSTER VIEWING II

commencing anti-TNF. Demographic data, Bath AS Disease Activity knowledge of specific lesions associated with axial-SpA and knowl- Index (BASDAI) and spinal pain visual analogue scale scores were edge of international definitions of positive SI joint or spinal MRI in recorded. ESR and CRP were also recorded. axial-SpA. Results: In 70 Caucasian and 24 Asian SpA patients with comparable Results: Two-hundred and sixty-nine consultant radiologists from 131 age and sex, we observed no significant differences in baseline (73%) acute NHS trusts and health boards in the UK completed the BASDAI score, spinal pain score, ESR and CRP. Both groups had survey. One hundred and eighteen radiologists worked in England, similar response rates (>80%) and reduction of inflammatory markers seven in Scotland, four in Wales and two in Northern Ireland. All but after treatment with anti-TNF at 6 months. However there was an one radiologist had access to an MRI scanner. Waiting time for an MRI inferior post treatment reduction of BASDAI and spinal pain scores at scan was less than 2-months in 118 (90%) of the trusts/health boards. early (3–9 months) and late (12–24 months) time points in the Asian Protocols: 256 (91%) used T1 and short Ti inversion recovery or population compared with the Caucasians. equivalent fat saturation sequences but 172 (64%) also used T2 Conclusion: Our findings suggest a significant difference exists in level sequences in addition, and 29 (11%) of radiologists used contrast in of response to anti-TNF between Caucasian and Asian AS patient SpA MRI protocols. Fourteen radiologists (5%) routinely only scanned groups. These differences were observed using the self-reported the SI joints (SIJ), 89 (33%) scanned the SIJ and lumbar spine only, 79 BASDAI and spinal pain scores at different time points of their treatment. (29%) scanned the thoracolumbar spine and the SIJs and 81 (30%) Both groups had a similar reduction in ESR and CRP with treatment. To scanned the whole spine and SIJ. The mean time to perform a SpA dissect if the inferior responses among our Asian population are due to a MRI protocol was 34 min. Diagnostic features and disease awareness: lower pain threshold, further sub-analysis would need to be done on the Only 202 (75%) of radiologists were aware of the term axial-SpA. BASDAI scoring components. An awareness of possible ethnic or Forty-eight (18%) did not use subchondral bone marrow oedema of cultural influences on disease activity may assist us with interpreting the SIJ to help diagnosis axial-SpA and 48 (18%) did not use the differences in prognosis and responses to anti-TNF drugs. presence of inflammatory vertebral corner lesions to assist in Disclosure statement: The authors have declared no conflicts of diagnosis. Only 84 (31%) were aware of the ASAS definition of a interest. positive SIJ MRI and as few as 67 (25%) were aware of the ASAS positive definition of the spine. 219. THE RADIOLOGISTS’ UNDERSTANDING OF AXIAL-SPA Conclusion: These data provide evidence of the diverse practices AND THE USE OF MRI IN THE ASSESSMENT OF DISEASE: IS among UK radiologist when assessing axial-SpA. It highlights the need IT TIME FOR A CONSENSUS? for better education of radiologists of the condition of axial-SpA, and typical MRI lesions of axial-SpA based on international definitions of 1,2 3 4 Alexander N. Bennett , Amer Rehman and Daljit Kaur-Papadakis positive scans. The data support the notion that there should be a UK 1 Academic Department of Military Rehabilitation, DMRC Headley radiology and rheumatology consensus on the most appropriate MRI Court, Defence Medical Rehabilitation Centre, Headley Court, protocol in the assessment of axial-SpA. 2 Epsom, Department of Rheumatology, Leeds Institute of Rheumatic Disclosure statement: A.N.B. has acted as a consultant for Pfizer and and Musculoskeletal Medicine, Leeds and 3Department of Radiology, UCB; has received honoraria from AbbVie, UCB, Pfizer, Novartis and Countess of Chester Hospital, Chester, 4Medical Affairs- MSD; and has received research funding from Pfizer for previous Immunology, AbbVie Ltd, Maidenhead, UK research not related to this abstract. A.R. has received honoraria from AbbVie. D.K.-P. is an employee of AbbVie. Background: MRI plays a major role in the assessment of axial-SpA. The Assessment in Spondyloarthritis International Society (ASAS) 220. PREDICTING SUCCESSFUL LONG-TERM TREATMENT classification criteria for axial-SpA include the use of MRI, and are WITH TUMOUR NECROSIS FACTOR ALPHA INHIBITORS IN accompanied with the definitions of a positive MRI. There are, PATIENTS WITH PSORIATIC ARTHRITIS however, no guidelines recommending the optimum MRI protocol. 1 2 3 Anecdotal evidence suggested varied knowledge of axial-SpA among Karen M. Fagerli , Kath D. Watson , Jon Packham , Deborah P. 2,4 2 UK radiologists and that many different MRI protocols are used in M. Symmons and Kimme L. Hyrich 1 different UK centres. Our aim was to assess the knowledge of axial- Department of Rheumatology, Diakonhjemmet Hospital, Oslo, SpA among UK radiologists, and to investigate current common Norway, 2Arthritis Research UK Centre for Epidemiology, University practice of the use of MRI in the assessment of axial-SpA in the UK. of Manchester, Manchester, 3 Institute of Science and Technology in Methods: Six-hundred and ninety-nine UK consultant radiologists Medicine, Keele and 4 NIHR Manchester Musculoskeletal Biomedical from 180 UK National Health Service (NHS) trusts (England) or health Research Unit, Manchester, UK boards (Scotland/Wales/Northern Ireland) were invited to complete a 15-min online survey. This included questions on availability of MRI Background: The short-term efficacy of TNF-a inhibitor (TNFi) therapy scanners, familiarity with axial-SpA, local MRI protocols for axial-SpA, in patients with PsA is well documented. In observational studies,

220 TABLE 1. Baseline variables and logistic regression predicting continued treatment at 5 years Baseline Univariate analysis Final multivariate model

OR (95% CI) OR (95% CI) P-value Female, n (%) 334 (53.4)a 0.52 (0.38, 0.71) 0.52 (0.37, 0.72) <0.000 Age, years 45.8 (11.1)a 1.00 (0.99, 1.02) 1.01 (1.00, 1.03) 0.12 Disease duration, years 12.4 (8.6)a 1.01 (0.99, 1.03) — — Previously used DMARDs 3 (2–4)b 0.93 (0.84, 1.04) —TNFi, n (%) —— —Etanercept 345 (55.2) REF — — —Infliximab 181 (29.0) 0.52 (0.36, 0.75) 0.53 (0.36, 0.78) 0.001 —Adalimumab 99 (15.8) 0.92 (0.59, 1.44) 0.95 (0.60, 1.50) 0.83 Current smoker, n (%) 289 (46.2) 0.65 (0.42, 1.00) — — Somatic comorbidityc 289 (46.2) 0.59 (0.42, 0.81) 0.55 (0.39, 0.78) 0.001 Depression 121 (19.4) 0.78 (0.52, 1.16) — — Comedication, n (%) —— —None 180 (29.1) REF —MTX combinationd 370 (59.2) 0.90 (0.63, 1.28) — — —Other 73 (11.7) 0.57 (0.32, 1.00) — — Baseline steroid use, n (%) 76 (22.0) 0.93 (0.64, 1.36) — — Global (0–100) 71.2 (20.9)a 1.00 (0.99, 1.01) — — DAS 28 6.09 (1.15)a 1.01 (0.88, 1.16) — — Tender joints (28-joint count) 13 (7–19)b 0.98 (0.96, 1.00) — — Swollen joints (28-joint count) 8 (4–13)b 1.01 (0.98, 1.03) — — ESR (mm/h) 33.5 (18.5–57)b 1.00 (1.00, 1.01) — — HAQ (0–3) 1.88 (1.38–2.25)b 0.67 (0.52, 0.87) — — Reason for discontinuation —Inefficacy, n (%) 115 (34.5) —Adverse events, n (%) 96 (28.8) —Other/missing, n (%) 122 (36.6) a b c Mean (S.D.). Median (interquartile range). 1 of (previous or current) hypertension, angina, MI, stroke, epilepsy, asthma, chronic obstructive airway disease, peptic ulcer disease, liver disease, renal disease, tuberculosis, demyelinating disease, diabetes, cancer. dAlone or in combination with other DMARD per unit increase (in continuous variables). OR: odds ratio. POSTER VIEWING II Wednesday 29 April 2015 i135

effectiveness has mainly been explored in the short-term (1–3 years) calculated using age and gender specific cancer rates for the general and predictors of improved short-term drug survival include male English population for (i) overall cancer risk (ICD-10: C1–C9) and (ii) gender, concomitant MTX use, etanercept (ETN) use and high CRP. NMSC (C44) for the whole cohort and separately for men and women. The aim of this analysis was to identify predictors of long-term (5 years) Results: 709 patients contributed 5956.5 patient-years of follow up: persistent treatment with TNFi in patients with PsA. the mean (S.D.) age was 45.7 (11.2) and median disease duration (IQR) Methods: We included PsA patients registered with the British Society was 11 (6–17) years (Table 1). Mean (S.D.) DAS for 28 joints was 6.0 for Rheumatology Biologics Register starting their first TNFi (recruited (1.2). 11 (1.6%) patients had a cancer registered prior to baseline, none 2002–06). Demographics, disease activity (joint counts, patient- of which had a further cancer. Nearly all (98%) had previous or current reported outcomes and inflammatory markers), disability, comorbid- exposure to MTX at baseline and 45.6% had previous or current ities and previous/current treatments were recorded at baseline. exposure to ciclosporin. Information on baseline PUVA exposure was Follow up (biannual for 3 years and then annually) includes changes in only available for 163 (23%) patients and 11 (6.7%) had been exposed. treatment, disease activity and adverse events. We identified patients 34 cancers in 32 patients were observed, including 19 skin cancers (15 who had continued their initial treatment for 5 years (allowing pauses NMSC and 4 melanomas). Overall, there was no increased risk of <90 days). Univariate logistic regression was used to identify factors malignancy observed in this cohort (SIR 0.94, 95% CI 0.65, 1.34) associated with 5 years of persistent therapy. Covariates included age, compared with the general population. There was a significantly disease duration, gender, number of previously used non-biologic increased incidence for NMSC although the precision of the estimate DMARDs, somatic comorbidity, depression, TNFi-type, comedication, was low (SIR 2.12, 95% CI 1.19, 3.50) likely reflecting low number of steroid use, DAS 28, ESR, patient global assessment, tender and events. swollen joints, current smoking and HAQ. Age, gender and variables Conclusion: In this population of severely active PsA patients with P-value of < 0.25 were included in a multivariate model and a recruited early in the TNFi era, the overall incidence of malignancy backward section was performed to fit the final model. was reassuringly similar to that of the general population. Incidence of Results: We included 625 patients starting TNFi (Table 1). At 5 years, NMSC was increased, which may be related to PsA itself, skin 292 (46.7%) patients were still on their initial treatment. Gender, TNFi- psoriasis, phototherapy and/or immune-modulatory treatment. type, number of previously used DMARDs, somatic comorbidity, Disclosure statement: K.L.H. has received honoraria from Pfizer for depression, tender joints, current smoking and HAQ were relevant attending a meeting and speaker fees from AbbVie and Pfizer. All other predictors in univariate analysis (P < 0.25). Concomitant MTX was not authors have declared no conflicts of interest. a predictor, either in the whole cohort or when stratified by TNFi-type, but only 13 patients received infliximab (IFX) as monotherapy. Male gender, absence of baseline somatic comorbidity and use of ETN or 222. EXPLORING THE IMPACT OF FATIGUE ON ACTIVITY adalimumab (ADA) rather than IFX were independently associated with LEVELS AND QUALITY OF LIFE IN PEOPLE WITH persistent treatment at 5 years (Table 1). Previously used DMARDs, ANKYLOSING SPONDYLITIS depression, HAQ, tender joint count and current smoking were not Clodagh Fitzpatrick1, Deirdre Connolly1 and Finbar O’Shea2 significant predictors in the multivariate model. 1Occupational Therapy, Trinity College Dublin and 2Rheumatology, Conclusion: Among this severe cohort of patients with PsA who first St James’ Hospital, Dublin, Ireland initiated TNFi prior to 2007, almost 50% were still on their initial treatment at 5 years. The only patient characteristics predicting this Background: Fatigue in AS, has been found to impact on functioning were gender and baseline somatic comorbidity which limits applic- and quality of life. To date no Irish studies have been performed ability to clinical practice. Concomitant MTX was not a significant assessing the impact of fatigue on activity participation, thus the main predictor of long-term treatment persistence, suggesting an absence aim of this study was to explore experiences of fatigue and how it of a beneficiary effect across all TNFi therapies. impacts on activity participation in an Irish cohort of patients with AS. Disclosure statement: K.L.H. has received honoraria from Pfizer for Methods: Ethical approval was received from the Tallaght/St James’s attending a meeting and speaker fees from AbbVie and Pfizer. All other Hospital research ethic committee. A mixed methods design was authors have declared no conflicts of interest. employed. The quantitative measures used were the Frenchay Activities Index (FAI), Fatigue Severity Scale (FSS), Multidimensional 221. RISK OF CANCER IN PATIENTS WITH SEVERE Assessment of Fatigue (MAF), Bath AS Disease Activity Index PSORIATIC ARTHRITIS REQUIRING TUMOUR NECROSIS (BASDAI), Bath AS Functional Index (BASFI), Total Pain Numeric FACTOR ALPHA INHIBITION Rating Scale (NRS) and the AS Quality of Life questionnaire (ASQoL). The qualitative data were collected using semi-structured interviews to 1 2 2 3 Karen M. Fagerli , Louise K. Mercer , Kath Watson , Jon Packham , explore in depth personal perspectives of fatigue in AS. 2,4 2 Deborah P. M. Symmons and Kimme L. Hyrich Results: Informed consent to participate was received from 50 1 Department of Rheumatology, Diakonhjemmet Hospital, Oslo, patients with a definite diagnosis of AS who then completed Norway, 2Arthritis Research UK Centre for Epidemiology, University questionnaires. According to the Multidimensional Assessment of of Manchester, Manchester, 3Institute of Science and Technology in Fatigue (MAF) measure, significantly high fatigue levels (a score of over Medicine, Keele University, Keele and 4NIHR Manchester 21 out of 50) were found in 38% of participants in the study. Activity Musculoskeletal Biomedical Research Unit, Manchester, UK levels were high with a mean score of 31.86 out of 45 (S.D. 7.14) in the Frenchay Activities Index (FAI). Lowest activity participation levels Background: Few studies have explored risk of cancer in PsA. There were found in the leisure/work category with a mean score of 9.68 out are concerns that the risk may be raised, not only by the primary of 15 (S.D. 3.11). Mann Whitey U statistical analysis revealed disease, but also by the treatments given including conventional significant differences (P 0.05) between MAF scores (over and disease-modifying treatments (especially ciclosporin), tumour necrosis under 21) in activity participation (P ¼ 0.008), disease activity factor inhibitors (TNFi) and phototherapy. Skin psoriasis itself is (P ¼ 0.000), functional ability (P ¼ 0.015), total pain (P ¼ 0.001) and associated with an increased risk of non-melanoma skin cancer quality of life (P ¼ 0.000). Interviews found that disrupted sleep due to (NMSC). Our objective was to compare the incidence of cancer among pain causes fatigue. Concentration in work, energy levels and a cohort of patients with severe PsA patients receiving TNFi to that in motivation to engage in social activities were all affected by fatigue. the general population. Strategies helpful in managing fatigue included sleeping when Methods: All patients with PsA starting a TNFi in the British Society for possible, having a sleep routine and keeping active. It was reported Rheumatology Biologics Register (BSRBR, recruited 2002–06) were that health professionals do not address fatigue management and that included. Cancers were identified by flagging patients with the national it was often a minor topic in written information. cancer register which reported using the International Classification of Conclusion: This study stresses that fatigue has a notable impact on Diseases version 10 (ICD-10). All patients were followed from disease activity, pain, quality of life and participation in work and registration (start of TNFi) until death or 31 December 2012, whichever leisure activities. More input is required from health professionals to came first. Standardized incidence ratios (SIR) with 95% CI were assist with education on sleep hygiene and fatigue management.

221 TABLE 1. Overall and non-melanoma skin cancer standardized incidence ratios Overall (n ¼ 709) Male (n ¼ 331) Female (n ¼ 378) Total follow up, person-years 5956.5 2745.8 3210.7 O/E SIR (95% CI) 0/E SIR (95% CI) 0/E SIR (95% CI) All malignancies 34/36.2 0.94 (0.65, 1.34) 16/15.1 1.06 (0.61, 1.72) 18/21.1 0.85 (0.51, 1.35) NMSC 15/7.1 2.12 (1.19, 3.50) 6/3.3 1.79 (0.66, 3.90) 9/3.7 2.41 (1.10, 4.58) E: expected; NMSC: non-melanoma skin cancer; O: observed; SIR: standardized incidence ratio. i136 Wednesday 29 April 2015 POSTER VIEWING II

Disclosure statement: The authors have declared no conflicts of long-term safety issues, and the impact on quality of life in the real interest. world, i.e. in non-trial populations. In 2012, the British Society for Rheumatology Biologics Register for AS (BSRBR-AS) was established to monitor the safety of these treatments and to assess their effect on 223. USE OF REMOTE CONSULTATION IN THE quality of life and other outcomes. The aim of the current analysis MANAGEMENT OF STABLE PATIENTS RECEIVING was (i) to characterize first 1000 patients recruited to the study; and BIOLOGICAL THERAPY FOR ANKYLOSING SPONDYLITIS (ii) to identify any differences between biologic and non-biologic Claire E. Harris1, Rhys J. Hayward1 and Andrew C. Keat1 patients. 1Rheumatology, London North West Healthcare NHS Trust, Methods: Biologics-naı¨ve patients who meet the Assessment in Harrow, UK Spondyloarthritis International Society imaging definition of axial-SpA are recruited from rheumatology departments across the UK and Background: Biologic treatment has revolutionized management of classified as either biologics patients (those commencing Adalimumab AS but has added to the increasing burden of rheumatology clinics. or Etanercept), or non-biologic patients. Clinical data are extracted Monitoring requirements also place substantial time and cost burdens from medical records, including measures of physical function [Bath on patients, many of whom are now well, active and busy. Much of the AS Functional Index (BASFI)], laboratory markers (ESR, CRP, HLA- assessment of AS patients depends on patient-reported outcome B27) and presence of extra-spinal manifestations. Patient question- measures (PROMs) rather than clinical examination. These PROMs, naires collect data on disease activity [Bath AS Disease Activity Index Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASDAI)], pain, fatigue (Chalder Fatigue Scale) and quality of life (BASFI), visual analogue scale (VAS) for spinal pain and the Work and (ASQoL 0–18). Productivity Activity Index, can be completed online by using Talking Results: Data were available for 981 patients [73% male; mean age 50 AS (provided free by AbbVie) and face-to-face discussion enabled by years (S.D.: 15)], with a mean disease duration of 23 years (15). Mean applications such as Skype. We have therefore piloted telemedicine disease activity (BASDAI) and physical function (BASFI) scores were clinics for some patients receiving biologic therapy, by using a 4.8 (2.6) and 4.8 (3.0), respectively. 22% of patients had a history of combination of Talking AS and Skype to assess the value of uveitis, 11% had IBD and 11% had psoriasis. The mean quality of life telemedicine consultations alternating with regular clinic visits. (ASQoL) score was 8.5 (5.8) and 50% of patients reported moderate or Methods: AS patients, who had received biologic treatment for more severe fatigue. Compared with those in the non-biologics cohort, than 12 months and were well with BASDAI of 4 and normal CRP those starting anti-TNFa therapy were younger (45 years vs 53 years; were invited to participate in a telemedicine consultation instead of P < 0.001); more likely to be unemployed due to ill health (18% vs 7%; their next routine consultation. Each patient consented to use Talking P < 0.001) and smoke (32% vs 15%; P < 0.001). As expected, given AS and confirmed their Skype name, telephone number and email treatment guidelines, those commencing biologic therapy experienced address. The telemedicine clinics were planned outside regular clinic higher disease activity (BASDAI 6.3 vs 4.2; P < 0.001). They also times and used two computers, one showing Talking AS and blood reported poorer physical function (BASFI 6.3 vs 4.1; P < 0.001) and results, the other being the Skype interface. The patient’s notes were quality of life (ASQoL 12.2 vs 6.8; P < 0.001). They were also more available. At the end of the consultation patients were asked to likely to report moderate/severe fatigue (69% vs 41%; P < 0.001) complete a short questionnaire about their experience via although no difference was demonstrated in the proportions of SurveyMonkey. patients with extra-spinal manifestations. Results: 30 patients were invited to participate; 15 accepted. In all Conclusion: Patients commencing biologic therapy in BSRBR-AS cases a clinical evaluation was made and results of PROMs (13) and exhibit overall worse disease with regard to both clinical and patient- recent blood results (10) were available. New problems were disclosed reported measures. Compared with published AS trial populations, the by two patients and managed appropriately. A GP letter was BSRBR-AS biologic cohort is older, with longer disease duration and generated and a follow-up appointment made. Average consultation worse physical function. This study reflects a real-life disease time was 14.3 (6–40) min; including time spent overcoming technical phenotype and provides an opportunity to assess the clinical efficacy, issues with 3 patients. Eight patients were at work and 7 at home; 12 safety and long-term outcomes of anti-TNFa therapy outside rando- patients completed the online survey; 11 found it not at all disruptive; 6 mized clinical trials. took no time off work, with 5 taking less than 1 h off in total; 10 had Disclosure statement: G.T.J. has received research grants from taken half a day and one a whole day off for their last clinic visit; and all Pfizer and AbbVie. N.B. has received consulting fees from MSD and were very satisfied or satisfied with the consultation. Pfizer; has received honoraria from Roche and Pfizer; has served on Conclusion: In selected patients telemedicine consultations provided speakers’ bureaus on behalf of Roche and Pfizer; and has received similar care to a traditional visit with a substantial saving in terms of research grants from Pfizer. L.K. has received funding from AbbVie to time lost from work, travel and parking costs for the patients. New attend meetings. G.J.M. is a member of Pfizer’s Competitive Research problems disclosed during the consultations were managed as Grant committee; and has received research funding from Pfizer and normal. All those who participated said they would be happy to use AbbVie. All other authors have declared no conflicts of interest. telemedicine again. Setting up the remote clinic was time-consuming for clinicians but this may be reduced with service development. There was no additional service cost. Collection of data was incomplete but 225. WORKING IT OUT: A LONGITUDINAL QUALITATIVE comparable to our experience in a conventional clinic. STUDY CONCERNING WORK ISSUES IN NEWLY DIAGNOSED AS/AXIAL-SPA Disclosure statement: C.E.H. has received consulting fees from MSD; has received honoraria from AbbVie, MSD, Pfizer and UCB; has Jane Martindale1,2 and Lynne Goodacre3 received research funding from Pfizer; and has received support for 1Physiotherapy, Wrightington Wigan and Leigh NHS Foundation travel from MSD and Pfizer. R.J.H. has received support for travel from Trust, Wigan, 2Lancaster Health Hub, Lancaster University, Lancaster MSD and Pfizer. A.C.K. has received consulting fees and honoraria and 3NHS Research and Development North West, NHS Research from AbbVie, MSD, Napp, Pfizer and UCB; has served on speakers’ and Development North West, Manchester, UK bureaus on behalf of AbbVie, MSD, Pfizer and UCB; has received research grants from AbbVie and Pfizer; and has received support for Background: AS/axial-SpA affects younger people potentially dis- travel to meetings from AbbVie and Pfizer. rupting or even curtailing an individual’s ability to remain in work. Little is known about the impact on working ability pre-diagnosis and the 224. THE BRITISH SOCIETY FOR RHEUMATOLOGY impact that having a diagnosis can make. We aimed to conduct a BIOLOGICS REGISTER FOR ANKYLOSING SPONDYLITIS: longitudinal in-depth exploration into experiences in newly diagnosed CHARACTERISTICS OF STUDY PARTICIPANTS participants both at diagnosis and a year later. We sought to gain insights into experiences of pre and post diagnosis highlighting both 1 1 1 2 Gareth T. Jones , Linda E. Dean , Neil Basu , Lesley Kay , the positive and negative impacts perceived while working with this 3 4 1 Ejaz Pathan , Roger D. Sturrock and Gary J. Macfarlane condition. 1 Epidemiology Group, Musculoskeletal Research Collaboration, Methods: Within this single-cohort qualitative study located within an University of Aberdeen, Aberdeen, 2Department of Rheumatology, interpretive phenomenological paradigm 10 people newly diagnosed Freeman Hospital, Newcastle upon Tyne, 3Department of with AS/axial-SpA participated in semi-structured interviews at Rheumatology, Aberdeen Royal Infirmary, Aberdeen and 4Centre for diagnosis and repeated a year later. The interviews were recorded, Rheumatic Diseases, University of Glasgow, Glasgow, UK transcribed and analysed thematically using a framework analysis. Ethical approval and informed consent were obtained. Background: The use of biologic agents in AS is common: data from Results: Analysis led to the overarching theme of Working it Out which the Scotland Registry for AS (SIRAS) suggest that around one-third of was underpinned by five key themes: Sensing what to do describes patients have, at some point, received anti-TNFa therapy. However, how participants prior to diagnosis were able to recognize and sense there are several unanswered questions regarding their use, including how their symptoms had already forced them to make changes and POSTER VIEWING II Wednesday 29 April 2015 i137

adaptations in their work place; Realizing what works provides insights Disclosure statement: A.M. has received speaker fees from AbbVie into how participants had been able to recognize the beneficial and MSD. A.G. has received research funding from AbbVie. G.C. was adjustments made in the work place particularly with remaining active; paid by AbbVie to design and conduct the survey. Risk/benefits of disclosure explores the risk: benefit assessments which participants had undertaken with regard to disclosing that they had back 227. RETROSPECTIVE STUDY ON THE RESPONSE AND pain symptomology; Worries about work focuses on how participants SIDE-EFFECT PROFILE OF THE SECOND BIOLOGICS IN THE had specific worries about maintaining their ability to remain in their jobs; MANAGEMENT OF PERIPHERAL PSORIATIC ARTHRITIS and Affirmation and empowerment describes how almost every participant had identified and affirmed the changes that they had Veena Patel1, Ebrahim Mulla2 and Alison Kinder1 made in the work place during the first year following diagnosis. 1Rheumatology Department, Leicester Royal Infirmary NHS Trust and Conclusion: Living with a diagnosis for a year provides reinforcement 2Rheumatology Department, NHS Trust, Leicester, UK of the benefits gained by the positive intuitive changes and adapta- tions made pre-diagnosis. Participants had been able to sense what to Background: PsA is a chronic inflammatory arthropathy affecting up do and realized what works in regard to maintaining the expectations to 40% of patients with psoriasis. British Society of Rheumatology for their job role resulting in feelings of empowerment. Additionally, (BSR) and EULAR recommend anti-TNF therapy for those patients with diagnosis gives legitimization to remaining as active as possible within active disease and who have failed with at least two conventional the work place although this was tempered with issues of disclosure to DMARDs. The PsA response criteria (PsARC), composite arthritis colleagues and/or managers as to why this was essential. Even with outcome measure are recommended to assess the clinical response to diagnosis it appears that a risk/benefit assessment continues to be the DMARDS and biologics therapy. BSR and EULAR recommend made as to the level of disclosure that participants are prepared to using alternative anti-TNF therapy if the first anti-TNF treatment fails make which was dependant on individualized circumstances. Adding either due to inefficacy or adverse events. To this end, this retro- to this dilemma was the frustration of the lack of understanding of what spective study aims to share our experience of treating PsA patients AS/axial-SpA is and the fear of stigmatization. At diagnosis clinicians with biologics. should not underestimate the positive adjustments that people are Methods: All patients in Leicestershire who were referred to a PsA intuitively making and need to reinforce these adjustments accom- biologic clinic from January 2011 to December 2012 were included. panied with an appreciation about the lack of awareness of this Patients who started on biologics were identified using biologic invisible condition. database and data were collected from clinical notes using a data Disclosure statement: J.M. has received honoraria for lectures from collection tool. We included all patients who had the clinical diagnosis Pfizer and AbbVie. The other author has declared no conflicts of of peripheral PsA and excluded patients with axial and seropositive interest. inflammatory arthritis. The anti-TNFs used were infliximab, adalimu- mab, etanercept and golimumab either alone or in combination with DMARDs. 226. A CROSS-SECTIONAL SURVEY ON INFLAMMATORY Results: Out of 203 patients with peripheral PsA referred to biologics BACK PAIN: A COMMON FINDING IN PATIENTS WITH clinic, 166 patients were started on biologics treatment after reviewing CHRONIC BACK PAIN? the inclusion and exclusion criteria. The proportions were 42%females Arumugam Moorthy1, Alan Gade2 and Gordon Crawford2 and 58% male, with mean duration of disease before starting the first 1Department of Rheumatology, University Hospitals of Leicester NHS biologics was 10 years. Most common first biologics used is trust, Leicester and 2Patient Direct, Glasgow, UK adalimumab (54%) followed by etanercept (33%). Nearly 78% (130/ 166) of patients continued on first biologics with significant response in Background: We aimed to assess a number of patients who met the PsARC indices and 22% (36/166) failed to continue due to various standard criteria for inflammatory back pain (IBP) within a cohort of reasons with the majority being the adverse reaction (25%) and patients with chronic back pain, and to evaluate the treatment they inefficacy (22%). Among 36 patients, 64% (23/36) were started on received second biologics (infliximab 43% and adalimumab 34%) and 61% (14/ Methods: A cross-sectional survey of adults (18 years) with chronic 23) had significant response in PsARC indices and continued. 77% (7/ back pain for more than 3 months was conducted between December 9) patients were started on a third anti-TNF: one continued and the rest 2013 and May 2014 to identify patients with IBP. The survey consisted stopped due to various reasons but inefficacy being the main reason of an online questionnaire-based survey supplemented by telephone for the majority (42%). response. Respondents were recruited throughout the UK using social Conclusion: We conclude that the majority of the first anti-TNF media (Facebook) and national newspaper (Daily Mail) advertisements. therapies in peripheral PsA are effective and well tolerated. Patients in The primary outcome measure was the number of respondents with our cohort had good response to the second and third-line anti-TNF chronic back pain who fulfilled the Assessment in Spondyloarthritis therapy also. There was statistically significant difference in the PsARC International Society (ASAS) and Calin diagnostic criteria for IBP. Other indices among all the first anti-TNF therapies except for the infliximab outcome measures included demographic data and analgesic which did not show a significant improvement of tender joints. There medications. was a significant inverse correlation between duration of the disease Results: The total number of recruited adults who completed the and good response for the first biologic therapy suggesting early survey was 586; 77.6% were through Facebook, 15.5% were through aggressive intervention will benefit patients. Major limitation of this newspaper advertising and the rest were friends and others. Over study was that the responses of patients on anti-TNFs were not three-quarters of respondents (77.6%) were female. Facebook considered along with DMARD. respondents (mean 40.5 years; median, 41.0 years) were younger Disclosure statement: The authors have declared no conflicts of than newspaper respondents (mean 68.0 years; median, 68.0 years). interest. Of the 586 respondents with chronic back pain, 52.0% satisfied the criteria for IBP, with 50% meeting the Calin criteria and 21% meeting 228. SECUKINUMAB, A HUMAN ANTI-INTERLEUKIN-17A the ASAS criteria. 110 patients met both criteria (19%). Of the 305 MONOCLONAL ANTIBODY, IMPROVES ACTIVE PSORIATIC respondents with IBP, 89% were younger than 40 years at onset, 77% ARTHRITIS AND INHIBITS RADIOGRAPHIC PROGRESSION: were female and 65% had experienced back pain for more than 5 EFFICACY AND SAFETY DATA FROM A PHASE 3 years. Overall, 27% of respondents reported having been informed by RANDOMIZED, MULTICENTRE, DOUBLE-BLIND, PLACEBO- at least one healthcare professional that their back pain was CONTROLLED STUDY associated with inflammation. Of these, 89 (57%) met the Calin criteria 1 2 3 4 and 39 (25%) met the ASAS criteria. The 39 respondents meeting the Hasan Tahir , Philip Mease , Iain B. McInnes , Bruce Kirkham , 5 6 7 ASAS criteria had been informed of the inflammatory nature of their Arthur Kavanaugh , Proton Rahman ,De´ sire´ e van der Heijde , 8 9 10 10 condition by a variety of healthcare professionals. 32 of the 39 Robert Landewe´ , Peter Nash , Luminita Pricop , Jiacheng Yuan , 11 11 respondents (82%) meeting the ASAS criteria reported extra-articular Hanno Richards and Shephard Mpofu 1 manifestations, including enthesitis (46%), uveitis (38%), IBD (30%), Rheumatology, Whipps Cross University Hospital, London, UK, 2 arthritis (26%), psoriasis (23%) and dactylitis (18%). Of the 39 Rheumatology, Swedish Medical Center and University of 3 respondents, 85% had been prescribed painkillers, 77% anti- Washington, Seattle, WA, USA, College of Medical, Veterinary and 4 inflammatory painkillers and 5% other medications; 10% were not Life Sciences, University of Glasgow, Glasgow, Rheumatology, receiving any prescription medication. Guy’s and St Thomas’ NHS Foundation Trust, London, UK, Conclusion: IBP was a relatively common finding in our cohort of 5Rheumatology, UC San Diego School of Medicine, San Diego, CA, patients with chronic back pain, with 21% satisfying the standard USA, 6Rheumatology, Memorial University, St John’s, NL, Canada, ASAS criteria for IBP. The social media respondents represented a 7Rheumatology, Leiden University Medical Centre, Leiden, younger population, which suggests that raising awareness of IBP 8Rheumatology, University of Amsterdam and Atrium Medical through social media may help to avoid delay in diagnosis. Centre, Amsterdam, The Netherlands, 9Rheumatology, University of i138 Wednesday 29 April 2015 POSTER VIEWING II

Queensland, Brisbane, Australia, 10Integrated Hospital Care, Schering-Plough, UCB and Wyeth; and has received research grants Rheumatology, Novartis Pharmaceuticals Corporation, East Hanover, from Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering- NJ, USA and 11Integrated Hospital Care, Rheumatology, Novartis Plough, UCB and Wyeth. P.N. has received honoraria from Novartis, Pharma AG, Basel, Switzerland AbbVie, Roche, Pfizer, BMS, Janssen and Celgene; and has received research grants from Novartis, AbbVie, Roche, Pfizer, BMS, Janssen Background: Secukinumab has demonstrated significant and rapid and Celgene. L.P. is an employee and shareholder of Novartis. J.Y. is efficacy in the treatment of psoriasis in two phase 3 studies. We an employee of Novartis. H.R. is an employee of Novartis. S.M. is an present the first randomized, multicentre, double-blind, placebo employee and shareholder of Novartis. (PBO)-controlled phase III study to assess the efficacy and safety of secukinumab in patients (pts) with PsA (FUTURE 1; NCT01392326). Methods: 606 adults with active, moderate to severe PsA were 229. A COMPARISON OF CLINICAL AND SYNOVIAL randomized to secukinumab or PBO. Pts on secukinumab received IMMUNOHISTOCHEMICAL CHARACTERISTICS BETWEEN 10 mg/kg i.v. loading dose at baseline, week 2 and week 4, then either PSORIATIC ARTHRITIS AND RHEUMATOID ARTHRITIS IN AN 75 mg s.c. (10 i.v.!75 s.c.) or 150 mg s.c. (10 i.v.!150 s.c.) every 4 EARLY ARTHRITIS COHORT weeks from week 8. PBO was given on the same schedules. Patients Wang Sin, G. Tan1, Maria Di Cicco1, Arti Mahto1, Ilias Lazarou1, naı¨ve to anti-TNF therapy (70%) and those intolerant of or Rebecca Hands1, Stephen Kelly1 and Costantinou Pitzalis1 inadequate responders to anti-TNF therapy (TNF-IR; 30%), were 1Rheumatology, Experimental Medicine and Rheumatology, Queen stratified across groups. Statistical analyses for the primary and Mary University London, London, UK multiple secondary endpoints used non-responder imputation (binary variables), mixed-effects repeated measures model (continuous Background: Elucidating pathological pathways in PsA may lead to variables) and linear extrapolation (radiographic data), following a the development of diagnostic and prognostic biomarkers and novel pre-defined hierarchical hypothesis testing strategy to adjust for treatment targets. Hence it is important to explore the biological multiplicity. differences between affected synovium in PsA and RA. Few Results: Demographics and baseline characteristics were balanced comparative data are available in early disease. This study aims to between groups. Both 10 i.v.!75 s.c. and 10 i.v.!150 s.c. demon- explore the pathobiology of early PsA by comparing the clinical and strated significantly higher ACR20 responses vs PBO at week 24 immunohistochemical characteristics between PsA and RA in early (50.5% and 50.0% vs 17.3%, respectively; P < 0.0001 vs PBO). All pre- disease. specified secondary endpoints, including dactylitis, enthesitis, SF36- Methods: Patients were selected from a prospective study containing PCS, HAQ-DI, DAS for 28 joints (DAS28)-CRP, ACR50, PASI 75, PASI clinical, serological and histological data on over 200 patients with 90 and mTSS score were achieved by week 24 and reached statistical early inflammatory arthritis. Patients with one or more swollen joint at significance; active dose separated from PBO as early as week 1 for baseline, who had symptoms for less than 12 months, and who were ACR20, DAS28-CRP and HAQ-DI. Drug exposure levels were similar in DMARD-naive, were recruited. Each patient underwent a clinical the secukinumab groups up to the primary endpoint due to i.v. loading. assessment of arthritis activity and an US-guided needle synovial Improvements in all primary and secondary endpoints were sustained biopsy of an affected joint. For this analysis, 20 patients diagnosed through week 52. At week 52, ACR 20/50/70 responses, using an clinically with PsA were included. Comparison was made with 20 observed analysis, were 66.9%, 38.4% and 25.6% for 10 i.v.!75 s.c. gender- and age-matched patients with RA. Categorical variables and 69.5%, 50.0% and 28.2% for 10 i.v.!150 s.c. In both TNF-naı¨ve were compared using the Fisher’s exact test. Continuous variables and TNF-IR groups, secukinumab demonstrated superiority at week were analysed using the Mann–Whitney U test. A P-value of <0.05 was 24 in ACR20/50/70, PASI 75/90, HAQ-DI, SF36-PCS, dactylitis and considered significant. enthesitis at both doses and the effect was maintained through week Results: Median disease durations for the PsA and RA cohorts were 4 52. Secukinumab significantly inhibited radiographic structural joint and 4.5 months respectively (P ¼ 0.862). There was no overall damage at week 24 vs PBO. AEs at week 16: 60.4% (10 i.v.!75 s.c.), difference in clinical features between early PsA and early RA, 64.9% (10 i.v.!150 s.c.) and 58.4% (PBO); non-fatal serious adverse including swollen/tender joint counts (SJC/TJC), VAS indices of event rates: 2.5%, 4.5% and 5.0%, respectively. Mean, median and Fatigue, Pain and Global Health, DAS and HAQ. There was no maximum exposures: 438.5, 456.0 and 721 days; AE/non-fatal serious difference in mean ESR or CRP. Synovial histology showed a trend adverse event rates: 78.1%/8.6% and 82.4%/12.9% in patients who towards lower synovitis scores and lower CD3, CD20, CD68 sublining received secukinumab 75 mg s.c. or 150 mg s.c., respectively, at any and CD138 counts in early PsA, which was not statistically significant. point in the study. However, stratification according to the histological synovitis score Conclusion: In this first phase 3 trial to evaluate highly selective IL- (Krenn score) did demonstrate significant differences in these two early 17A inhibition in pts with PsA, secukinumab provided rapid, clinically arthritis groups. A high histological synovitis score (Krenn 4–9), significant and sustained improvements in signs and symptoms, and reflected a significantly higher TJC, SJC, Pain VAS, Global Health inhibited joint structural damage. Secukinumab was well tolerated VAS and DAS for 28 joints (DAS28) compared with the PsA counter- through 52 wks. parts. In patients with a low Krenn score (0–3), PsA patients had a Disclosure statement: H.T. has received consulting fees from significantly elevated DAS28 score compared with the RA. Novartis, Lilly, MSD, AbbVie and Jansen. P.M. has received consulting Conclusion: At a group level, similarities exist between early PsA and fees from AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, RA in terms of clinical disease severity, levels of functional impairment, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB and Vertex; serum markers of inflammation and synovial markers of immune cell has served on speakers’ bureaus on behalf of AbbVie, Amgen, Biogen infiltration. However, when stratified by grade of histological synovitis, Idec, BMS, Crescendo, Janssen, Lilly, Pfizer and UCB; and has RA patients exhibit greater levels of clinical disease activity. Our received research grants from AbbVie, Amgen, Biogen Idec, BMS, findings suggest that while both conditions may present with similar Celgene, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB and clinical phenotypes, there are clear differences when patients are Vertex. I.B.M. has received consulting fees from Novartis, Amgen, stratified according to histological synovitis. Further analysis at a Janssen, BMS, Pfizer, UCB, AbbVie, Celgene and Lilly. B.K. has molecular level may be necessary to explore the relationship between received consulting fees from Novartis, AbbVie, BMS, Lilly and MSD; PsA and RA at different levels of disease activity and explain the has served on speakers’ bureaus on behalf of BMS, MSD and UCB; different histological segregation and relationship to clinical disease and has received research grants from AbbVie and UCB. A.K. has activity demonstrated in this study. received consulting fees from Novartis. P.R. has received consulting Disclosure statement: The authors have declared no conflicts of fees from Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, interest. Pfizer and Roche. D.v.d.H. is director of Imaging Rheumatology BV.; has received consulting fees from AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli Lilly, 230. EFFECTIVENESS OF SEQUENTIAL BIOLOGICS USE IN Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, ANKYLOSING SPONDYLITIS: RESULT OF A LARGE Otsuka, Pfizer, Roche and Sanofi-Aventis; and has received research RETROSPECTIVE SURVEY grants from AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli Lilly, Galapagos, GSK, Elaine Y. Tang1 and Preeti Shah1 Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, 1Rheumatology, North Western Deanery, Manchester, UK Roche and Sanofi-Aventis. R.L. is director of Rheumatology Consultancy BV, which is a registered company under Dutch law; Background: Since National Institute for Clinical Excellence (NICE) has received consulting fees from Abbott/AbbVie, Ablynx, Amgen, 2008, anti-TNF agents have made significant improvement in manage- AstraZeneca, BMS, Centocor, GSK, Novartis, Merck, Pfizer, Roche, ment of AS. On average more than one- half patients respond to first Schering-Plough, UCB and Wyeth; has served on speakers’ bureaus biologics. Switching to second biologics is discouraged by NICE. The on behalf of Abbott, Amgen, BMS, Centocor, Merck, Pfizer, Roche, aims of this audit were to assess if biologic treatment for AS started in POSTER VIEWING II Wednesday 29 April 2015 i139

compliance with NICE guidelines, to find out if biologic treatment is step test was performed twice (step tests 1 and 2) by each patient, being switched outside NICE guidelines and also to assess the with at least one week between tests. The predicted VO2max scores effectiveness of switching anti-TNF in real-life setting. were then compared with directly measured VO2peak assessed by a Methods: This is a retrospective survey across the North West to maximal cycle test. Bath AS Disease Activity Index (BASDAI) and Bath recruit all AS patients started on anti-TNF till June 2014. 15 sites AS Functional Index (BASFI) were obtained during the initial visit. participated and a total of 492 patients recruited. Pearson’s correlation coefficient (r) and intra-class correlation coeffi- Results: Baseline characteristics of patients are shown in Table 1. cient (ICC) were used to determine the validity and reliability of this 86% patients had radiological evidence, of which 54% X-ray, 20% submaximal test. MRI and 12% both X-ray and MRI. 80% patients had failure of two Results: 15 patients (11 male, 4 female), mean age 53 years (S.D.11 NSAIDs and a Bath AS Disease Activity Index of 4 on two occasions years) with controlled disease were recruited. Mean disease duration 12-week apart. First anti-TNF choice for majority of patients was was 16.6 years (S.D. 9.2 years), with a mean BASDAI of 3.6 (S.D. 2.1) adalimumab (60%), followed by etanercept (36%), infliximab (2%) and and mean BASFI of 3.7 (S.D. 2.5). There was excellent test-retest golimumab (1%). 12 weeks response rate was assessed to determine reliability [ICC 0.91 (95% CI 0.71, 0.97)] between step tests 1 and 2. if to continue or to stop the treatment. Data revealed 62% achieved The predicted VO2max scores from these tests correlated strongly adequate response, 15% inadequate response, 3% intolerant and with VO2peak (r ¼ 0.682 and r ¼ 0.718, respectively), and no differ- 20% had no response documented. 82% patients were started on ences were found between predicted VO2max from step tests 1 and 2 biologic monotherapy. 18% were on concomitant DMARDs, of which (30.2 8.8 and 31 7.9 ml/kg/min, respectively) and directly measured 62% on MTX. 26% patients were not on first biologic at the time of VO2peak (29.2 10.8 ml/kg/min). audit. The most common reason was intolerance (45%), followed by Conclusion: This is the first study demonstrating validity and reliability primary inefficacy (35%), secondary efficacy (7%), 13% due to other of the Siconolfi step test for predicting VO2max in axial-SpA patients. reasons including patient’s choice, newly diagnosed Crohn’s and The step test was well tolerated by patients. Thus, the Siconolfi step cancer. Two-thirds of patients (n ¼ 88) who failed first anti-TNF went test is an appropriate means of evaluating cardiorespiratory fitness in onto second biologics, which represents 18% of patients audited. Half axial-SpA patients in the clinic, as well as a suitable tool for assessing of them (n ¼ 48) switched to adalimumab, one-third (n ¼ 38) to the efficacy of interventions aimed at improving aerobic capacity in etanercept and two to golimumab. Four patients went on to have these patients. third biologics: three on etanercept and one on golimumab. For the Funding: This project was part funded by the European Social Fund, switchers, 58% of patients responded to second biologics, 3% through the Access to Masters programme. patients responded to the third biologics, 8% were awaiting assess- Disclosure statement: The authors have declared no conflicts of ment, 15% did not achieve adequate response, 16% no documented interest. response. For the switchers, 67% applied for funding to clinical commissioning (CCG) and approval was gained in all. Conclusion: In summary, 20% patients switched biologic and two- thirds responded. These real-life data support the use of sequential anti-TNF in AS for those who lack of response or intolerant to first SOFT TISSUE AND REGIONAL biologic. This had led to support at CCG level to switch and therefore MUSCULOSKELETAL DISEASE, signifies the need to update NICE guidelines. Disclosure statement: The authors have declared no conflicts of FIBROMYALGIA interest.

230 TABLE 1. Baseline characteristics of patients 232. CLUES TO RECOGNIZE FIBROMYALGIA FROM A Baseline characteristic Value PATIENT SELF-REPORT MULTIDIMENSIONAL HEALTH Age, median (IQR), years 48 (22–83) ASSESSMENT QUESTIONNAIRE AND PHYSICIAN Male,% 79 RHEUMDOC Disease duration, median, years 9 First assessment since anti-TNF, median (IQR), weeks 12 (3–56) Andra F. Negoescu1, Elena Nikiphorou1, Isabel Castrejon2 and Anti-TNF started after NICE (TA143), % 86 Theodore Pincus2 IQR: interquartile range; NICE: National Institute for Clinical Excellence. 1Rheumatology, Addenbrooke’s Hospital, Cambridge, UK and 2Rheumatology, Rush University Medical Center, Chicago, IL, USA

231. THE SUBMAXIMAL SICONOLFI STEP TEST RELIABLY Background: FM is characterized by widespread musculoskeletal ESTIMATES CARDIORESPIRATORY FITNESS LEVELS IN pain and a broad range of symptoms. FM generally is considered a PATIENTS WITH AXIAL SPONDYLOARTHROPATHY diagnosis of exclusion and may pose a diagnostic challenge, although it often is relatively easily recognized. We assessed whether informa- 1 2 1,3 1,3 Paul Thompson , Robert Caine , Jeanette Thom , Rebecca Law , tion from a two-page patient self-report multidimensional HAQ 2 1 2 Yasmeen Ahmad , Andrew Lemmey and Sarang Chitale (MDHAQ) and one-page physician RHEUMDOC checklist can serve 1 School of Sport, Health and Exercise Sciences, Bangor University, as strong clues to recognition of FM. 2 Bangor, Peter Maddison Rheumatology Centre, Betsi Cadwaladr Methods: All patients seen in one academic clinical setting complete a University Health Board, Llandudno, UK, 3School of Medical two-page MDHAQ in 5–10 min in the waiting area, prior to seeing the Sciences, University of New South Wales, Sydney, Australia and rheumatologist in the infrastructure of usual care. The MDHAQ 4North Wales Centre for Primary Care Research, Bangor University, includes physical function (FN) in 10 activities of daily living, three 0– Bangor, UK 10 visual analogue scales (VAS) for pain (PN), patient global estimate (PATGL), and fatigue (FT), a 60-item symptom checklist, and Background: Axial SpA patients have increased risk of cardiovascular demographic data. Scores were computed for RAPID 3 (0–30, i.e., disease (CVD), and this, in part, may be due to low levels of the sum of three 0–10 scores for FN, PN and PATGL), total number of cardiorespiratory fitness/aerobic capacity (VO2max). Maximal cardior- symptoms (0–60), and fatigue VAS. RHEUMDOC is a one-page espiratory fitness testing, regarded as the gold standard for determin- physician checklist with four 0–10 VAS for overall global patient ing VO2max, is impractical in the clinical setting; thus valid, and easy to status (DOCGL), and levels of inflammation (reversible signs) conduct, submaximal tests which predict VO2max are required. One (DOCINF), damage (irreversible signs) (DOCDAM), and neither inflam- such test, the Siconolfi step test has been validated in RA and SLE. mation nor damage (DOCNON) e.g. FM. Patients were analysed in four This study evaluated the test’s validity and reliability in axial-SpA diagnosis groups: RA, SLE, OA and FM. Mean MDHAQ and patients. RHEUMDOC scores were compared across the four groups, using Methods: Patients meeting the Assessment in Spondyloarthritis MANOVA, adjusting for age, symptom duration and education. International Society classification criteria for axial-SpA and attending Results: Analyses included 205 patients, 50 with RA, 66 with SLE, 57 the AS Clinic at the Peter Maddison Rheumatology Centre in North with OA and 32 with FM. Mean scores on each of the MDHAQ scales Wales were recruited. Exclusion criterion was previous known was highest in patients with FM, including number of symptoms, was ischaemic heart disease, age <18, clinically active disease, current significantly higher in FM than in other diagnoses (P < 0.01; Table 1). use of beta-blockers and inability to provide consent. The Siconolfi DOCGL also was highest in FM, while DOCINF was significantly lower. i140 Wednesday 29 April 2015 POSTER VIEWING II

232 TABLE 1. MDHAQ, RAPID 3 and symptom checklist in patients with RA, SLE, OA and FM Variable, score range All patients (n ¼ 205) RA (n ¼ 50) SLE (n ¼ 66) OA (n ¼ 67) FM (n ¼ 32) P-value (MANOVA) Mean (S.D.) Mean (S.D.) Mean (S.D.) Mean (S.D.) Mean (S.D.) MDHAQ function, 0–10 2.5 (1.9) 2.4 (2.0) 1.8 (1.7) 2.9 (1.9) 3.6 (1.9)* 0.0002 MDHAQ fatigue, 0–10 5.0 (3.0) 4.6 (3.2) 4.4 (3.1) 5.2 (3.0) 6.7 (1.8)* 0.0067 MDHAQ pain, 0–10 5.7 (3.0) 5.1 (3.1) 4.3 (3.2) 6.8 (2.2)* 7.6 (1.7)** <0.0001 Patient global, 0–10 5.0 (3.0) 4.5 (3.2) 4.0 (3.0) 5.4 (2.8) 7.1 (1.9)** <0.0001 RAPID3, 0–30 13.0 (7.2) 11.4 (7.4) 9.9 (7.3) 15.1 (5.8) 18.2 (4.4)*** <0.0001 Number of symptoms, 0–60 11.1 (8.5) 8.1 (8.5) 10.4 (8.2) 11.1 (7.1) 17.9 (8.2)*** <0.0001 Doctor measures —Physician global, 0–10 3.9 (2.1) 3.9 (2.2) 2.9 (2.1) 4.5 (1.6) 4.9 (1.8) <0.0001 —DOCINF, 0–10 1.5 (1.8) 2.4 (2.4) 1.4 (1.6)* 1.0 (1.5)** 0.8 (1.2)** 0.0003 —DOCDAM, 0–10 2.8 (2.1) 2.6 (2.2) 1.8 (1.8) 4.4 (1.6)*** 1.9 (1.8) <0.0001 —DOCNON, 0–10 2.1 (3.0) 0.6 (1.9) 1.1 (2.3) 2.1 (3.1)* 5.4 (2.2)*** <0.0001 *P < 0.05 **P < 0.01 ***P < 0.001 (P-values using RA as reference group). MDHAQ: multidimensional HAQ.

DOCINF was highest in RA, DOCDAM was highest in OA and at 6 months, and -1.50 (95% CI 7.82, 4.82) at 12 months. There were DOCNON was highest in FM (P < 0.001; Table 1). no differences in secondary outcome measures between the injection Conclusion: A diagnosis of FM is made on the basis of a patient groups at any time point. There was no significant interaction effect of history and physical examination. Nonetheless, simple patient and combined US-guided injection and physiotherapist-led exercise at the physician questionnaires can provide useful clues to recognize FM. primary endpoints of 6 weeks and 6 months. MDHAQ and RHEUMDOC in all patients could assist rheumatologists Conclusion: Physiotherapist-led exercise in SIS leads to greater to recognize FM. improvements in pain and function than providing a standardized Disclosure statement: The authors have declared no conflicts of advice and exercise leaflet. US-guidance confers no additional benefit interest. over unguided CS injection. Disclosure statement: The authors have declared no conflicts of interest. 233. CLINICAL EFFECTIVENESS OF EXERCISE AND CORTICOSTEROID INJECTION FOR SUBACROMIAL IMPINGEMENT SYNDROME: A RANDOMIZED CONTROLLED 234. HALF OF PATIENTS WITH FIBROMYALGIA HAVE TRIAL POSITIVE BIOPSY FOR SMALL FIBRE NEUROPATHY Edward Roddy1,2, Reuben Ogollah1, Irena Zwierska1, Euthalia Roussou1, Aleksandar Radunovic2, Istvan Bodi3, Praveen Datta3, Alison Hall1,2, Elaine M. Hay1,2, Sue Jackson4, Andreas Georgiou1 and Johnathan Chan4 Martyn Lewis1, Julie Shufflebotham1,5, Kay Stevenson1,4, 1Rheumatology, Barking Havering and Redbridge University Danielle van der Windt1, Julie Young1 and Nadine E. Foster1 Hospitals Trust, 2Neurology, Barts Health NHS trust, 3Clinical 1Research Institute for Primary Care and Health Sciences, Keele Neuropathology, King’s College London and 4Neurology, Barts and University, Keele, 2Rheumatology, Staffordshire and Stoke-on-Trent the London, London, UK Partnership Trust, 3Radiology, 4Physiotherapy, University Hospital of North Midlands and 5Physiotherapy, Staffordshire and Stoke-on- Background: FM can be primary or secondary related to other Trent Partnership Trust, Stoke-on-Trent, UK autoimmune diseases. Aiming to assess patients with primary FM for small fibre neuropathy (SFN) they were referred to neuromuscular clinic. Background: Subacromial impingement syndrome (SIS) is the most Methods: Patients assessed (May 2011–May 2014) and following common cause of shoulder pain. Management commonly involves verbal consent had a 3-mm skin punch biopsy specimen from two leg exercise and CS injection yet how these are best-delivered is sites: proximal, 20 cm below the right iliac crest; and distal, 10 cm uncertain. The SUPPORT trial investigated whether better outcomes above the right lateral malleolus. PGP9.5 is a pan-axonal marker. in pain and function are achieved with physiotherapist-led individua- Clinical data were obtained rating symptoms such as: night pain, sleep lized, supervised and progressed exercise rather than a standardized disturbance (SLD), wellbeing in the past week (WBPW) and past month advice and exercise leaflet; and US-guided subacromial CS injection (WBPM), FM pain and FM fatigue [all on a visual analogue scale (VAS) rather than unguided injection. of 0–10, where 10 ¼ worse positive]. Fabro fatigue scale (0–90), Methods: Design: 22 factorial randomized controlled trial. Adults Rotterdam emotional scale (30–120) ability to perform activities (8– with SIS were recruited from musculoskeletal interface services and 32; 8 best ability) and quality of life (7 point scale 7 ¼ unwell) were also randomized equally to one of four treatment groups: US-guided assessed. steroid injection and physiotherapist-led exercise; US-guided steroid Results: 25 patients (female:male 24:1) were examined. Mean (S.D.) injection and an exercise leaflet; unguided steroid injection and age of group was 45.8 years (11.6) range (20–73). The mean age of physiotherapist-led exercise; and unguided steroid injection and an symptom onset was 34.5 years (10.4; range 13–50 years) while the exercise leaflet. Outcomes were collected at 6 weeks, 6 and 12 mean age of diagnosis was 42.2 years (7.9; range 29–55 years). months by postal questionnaire. The primary outcome measure was Ethnicity analysis showed 14 Caucasian (56%), 8 Asian (32%), 2 the Shoulder Pain and Disability Index (SPADI), compared at 6 weeks African (8%), 1 Caribbean (4%). All 25 fulfilled the 2011 FM criteria, for the injection interventions and 6 months for the exercise while 21 fulfilled the 1999, i.e. 4 of 25 (16%) had fewer than 11/18 interventions. Secondary outcomes included SPADI pain and disability tender points. Two patients had past psoriasis and three had FX of subscales, current shoulder pain intensity, patient’s global impression psoriasis. Night pain (VAS) was 8.71 (1.06) and the SLD was 8.73 (1.6). of change, and pain self-efficacy. 250 participants were required to WBPW was 8.07 (1.8), WBPM was 8.7 (1.03) FM pain 8.5(1.3), FM detect a small-moderate effect size (0.4) in SPADI for the two main fatigue 8.6 (1.3), Fibrofatigue [mean (S.D.)] was 49.3 (18.4), sleep quality comparisons. Analysis was by intention-to-treat. was 8.5 (1.3), Rotterdam scale [mean (S.D.)] was 75.4 (20.7) and the Results: 256 participants were recruited (48% male, mean age 54 ability to perform activities was 20.8 (5.7). The total Quality of Life years), 64 per treatment group. Response rates for the primary [mean (S.D.)] was 5.38 (1.4). From the total of 25 patients biopsied and outcome were: 6 weeks, 94%; 6 months, 88%; and 12 months, 80%. tested for SFN, 13 patients (52%) were SFN positive, while 12 patients Greater mean improvement in total SPADI score was seen with (48%) were SFN negative. Numbers were small to enable statistical physiotherapist-led exercise than with the exercise leaflet at 6 months significance however the trend showed that the negative SFN group and 12 months: 3.02 (95% CI 3.00, 9.03) at 6 weeks, 9.48 (95% CI had older age of disease onset [38.6 years (6.5) vs 32.2 years (11.7)] 3.30, 15.65) at 6 months and 6.64 (95% CI 0.33, 12.96) at 12 months. older age at diagnosis [45.6 years (3.2) vs 40.4 years (9.1)] more FM Physiotherapist-led exercise led to greater mean improvement in fatigue [8.1 (1.7) vs 6.6 (4.1)] and better ability in performing activities SPADI pain subscale at 6 and 12 months, and in SPADI disability [23.5 (5.3) vs 18.5 (5.3) compared with negative SFN group. Similarities subscale at 6 months but not at 12 months. At 12 months, the were in the mean age [44.7 years (13.2) vs 46.7 years (10.4)], pain [8.6 physiotherapist-led exercise group showed a greater reduction in (1.5) vs 8.3 (1.3)], sleep quality 8.4 (1.5) vs 8.6 (1.4) and emotional current shoulder pain intensity, stronger self-efficacy beliefs and more functioning (Rotterdam symptom check list) [77 (22) vs 74.2 (20.9)] frequent patient reporting of being much or completely better. Within- Conclusion: Half of FM patients examined found positive for SFN group improvement in total SPADI was seen in both injection groups which is associated with potentially treatable conditions. but there were no significant between-group differences at any time Disclosure statement: The authors have declared no conflicts of point: 2.99 (95% CI 3.03, 9.00) at 6 weeks, 3.38 (95% CI 2.79, 9.56) interest. POSTER VIEWING II Wednesday 29 April 2015 i141

235. THE UTILITY OF ULTRASOUND IN CARPAL TUNNEL Patients rated their levels of pain, tingling, numbness and weakness on SYNDROME visual analogue scales (VASs). A US scan of the affected wrist was carried out by a second physician who was blind to the patients’ Anoushka C. Seneviratne1,2, Catherine Percy1 and 1 symptoms. Cross-sectional area (CSA) of the median nerve was Sundeept Bhalara measured at a standardized site. If appropriate, patients received an 1Rheumatology, Watford General Hospital, Watford and 2 intra-carpal injection of 25 mg of hydrocortisone and 0.1 ml of 1% Rheumatology, King’s College, London, UK lignocaine. VAS scores, BCTQ scores and cross-sectional area measurements were repeated at 4-week follow up. Background: Carpal tunnel syndrome (CTS) is the most common Results: 24 patients (20 females, 4 males; mean age 48 years) were upper limb entrapment neuropathy, causing symptoms of pain, included in the analysis. A satisfactory clinical response was achieved numbness, tingling and weakness, resulting from compression of the in 22 patients. Paired T-tests showed statistically significant improve- median nerve as it passes through the carpal tunnel in the wrist. ments in VAS scores, BCTQ scores and median nerve cross-sectional Diagnosis is clinical, but can be confirmed with nerve conduction area following injection. Dividing patients based on median nerve studies. US is an emerging complimentary aid to diagnosis, as cross-sectional area into mild (10–13 mm2) moderate (13–15 mm2) and additional information on nerve morphology, and carpal tunnel severe (15–18 mm2) a trend was observed where patients in the mild anatomy can be visualized. Steroid injections into the carpal tunnel group showed the greatest clinical response, while the severe group are an effective way of improving symptoms. We aimed to determine showed the least clinical response. whether the cross-sectional area of the median nerve on US reduced Conclusion: Our study in concordance with other series shows following an injection of steroid into the carpal tunnel. Additionally, we improvement in clinical symptoms and a reduction in median nerve aimed to find out whether the response to steroid injection could be cross-sectional area following steroid injection at early follow up. predicted by the initial cross-sectional area, the utility of this being to Baseline cross-sectional area measurements of the median nerve avoid unnecessary injection, and appropriately identify the need for greater than 15 mm2 are associated with a smaller degree of surgical referral, using US alone. symptomatic improvement and such patients may therefore be Methods: Patients were consecutively recruited from general practice identified early as surgical candidates. US is quick and safe and our referrals to our musculoskeletal service. Patients with a minimum 3- study supports its use as a valuable adjunct to aid the diagnosis of month history of symptoms suggestive of CTS were allocated into CTS and guide management decisions. clinics over a 6-month period. At consultation, the severity scale Disclosure statement: The authors have declared no conflicts of component of the Boston Carpal Tunnel Questionnaire (BCTQ) was interest. filled out. A history was taken and routine CTS examination was done. i142 Thursday 30 April 2015 POSTER VIEWING III

Background: Previous work from this unit has shown that a higher BASIC SCIENCE percentage body fat (%BF) has a negative effect on BMD. While it is well known that higher BMI confers protection from fragility fracture, negative correlations between %BF and BMD at both the lumbar spine and femoral neck were found in patients presenting for DXA scanning 2 236. EXPRESSION OF HUMAN CASPASE 5 IS ANALOGOUS with a BMI of less than 22 kg/m ; a threshold for poor bone health previously identified in this cohort. We aimed to examine patients TO MURINE CASPASE 11 AND IS ESSENTIAL FOR 2 NONCANONICAL IL-1b MATURATION presenting for DXA scanning who have a BMI >22 kg/m to see whether a similar relationship exists in this group. Steven J. Webster1, Sven Brode1, Louise O’Brien1, Lou Ellis1, Tim Methods: Data were collected between April 2004 and April 2010 from J. Fitzmaurice1, Matthew J. Elder1, John S. Hill Gaston1 and Jane patients who had been referred for DXA scanning. Patients with a BMI C. Goodall1 of >22 kg/m2 were split into quintiles of %BF and a linear regression 1Medicine, University of Cambridge, Cambridge, UK model was applied independently to %BF and lumbar spine BMD (mean of L1–L4) and femoral neck BMD (mean of both femurs) using Background: The instigation of an inflammatory response is crucial for Stata 11.2 for Windows. An adjusted model for BMI, age and sex was host defence against invading organisms. However, inappropriate or also applied. unregulated inflammation leads to the development of pathologies Results: 13 358 patients were included in the analysis of the such as auto-inflammatory syndromes, gout and post infectious forms relationship between body fat and lumbar spine BMD: they had a 2 of arthritis. The inflammatory cytokine IL-1b is a critical mediator of mean age of 64.39 years (S.D. 11.98) and a mean BMD of 1.08 g/cm inflammation and murine models deficient in IL-1b show protection (S.D. 0.19). 12 383 patients were included in the analysis of the against inflammation induced arthritis. Indeed, anti-IL-1b therapy is relationship between body fat and mean femoral neck BMD: they had 2 now successfully employed in the treatment of gout and auto- a mean age of 63.84 years (S.D. 11.92) and mean BMD of 0.86 g/cm inflammatory disease. Inflammasomes are protein scaffolds that (S.D. 0.14). There was a statistically significant negative association enable activation of inflammatory caspases which proteolytically (P < 0.05) between both body fat and lumbar spine BMD [coefficient cleave and activate the cytokines IL-1b and IL-18. It has been recently r ¼0.0008 95% (95% CI 0.0012, 0.0004)] and mean femoral neck demonstrated in murine macrophages that a non-canonical inflamma- BMD [coefficient0.002 (95% CI 0.0024, 0.0017)]. This relationship some requires caspase-11 for maturation of IL-1b in response to was also observed in a model adjusted for BMI, age and sex and was intracellular LPS or Gram-negative bacteria. Human caspases 4 and 5 present in all quintiles of body fat. Additionally, the adjusted R squared are orthologues of caspase-11 but it is unknown which is required for was high for both full regression models (lumbar spine BMD R2 ¼ 0.10, non-canonical IL-1b maturation in human myeloid cells. femoral neck BMD R2 ¼ 0.27). Methods: Human monocyte-derived dendritic cells (mDCs) were Conclusion: Patients with a BMI of >22 kg/m2 and with a higher %BF produced from differentiation of monocytes with GM-CSF and IL-4. are at an increased risk of lower BMD and therefore of fragility fracture. Murine bone marrow-derived macrophages (BMDMs) were produced This association has previously been found in patients with a BMI of by culturing cells in L929 conditioned medium. DCs were infected with <22 kg/m2 by this group. This relationship is independent of BMI which chlamydia or stimulated with lipopolysaccharide. Messenger RNA, has been shown to be protective for fragility fracture, and was still protein and IL-1b secretion were analysed by quantitative RT-PCR, present when adjusting for age and sex. This was an unexpected result western blotting and ELISA, respectively. Knock down of caspase-5 given that body fat has a role in storing oestrogen which has a role in was achieved using lentiviral delivery of small hairpin (sh)-RNA. bone formation. A possible explanation is that higher levels of body fat Results: LPS stimulation or Chlamydia trachomatis infection of sequester more oestrogen making it unavailable for conferring its anti- BMDMs resulted in expression of caspase-11 that was dependent resorptive effect on bone. on interferon receptor signalling and IRE1a RNase activity, indicating Disclosure statement: The authors have declared no conflicts of that endoplasmic reticulum stress enhanced expression. Furthermore, interest. CT-induced IL-1b processing was caspase-11 dependent. C. tracho- matis infection or LPS stimulation of mDCs resulted in significant increases in caspase-5 expression but not caspase-4. Furthermore, 238. CCN1 EXPRESSION BY FIBROBLASTS IS REQUIRED caspase-5 expression was TLR4 dependent and required both TRIF FOR BLEOMYCIN-INDUCED SKIN SCLERODERMA and MyD88 adaptor proteins and like caspase-11 was dependent on 1 1 IRE1a. Inhibiting IRE1a reduced C. trachomatis-induced IL-1b proces- Katherine Thompson and Andrew Leask 1 sing in mDCs while sh-RNA knockdown of caspase-5 reduced Dentistry, Western University, London, ON, Canada intracellular LPS- and C. trachomatis-induced IL-1b processing. Conclusion: Human caspase-5 is analogous to murine caspase-11 since Background: The cellular microenvironment is being increasingly its expression requires IRE1a RNAse activity, together with TRIF and appreciated as playing a key role in CTDs including scleroderma. MyD88 signalling. Furthermore, we have demonstrated that caspase-5 is Matricellular proteins, such as members of the CCN family (CCN1–6) essential for non-canonical processing of IL-1b and suggest that it is the play a key role in local modifications of cellular signalling and are true orthologue of caspase-11. We also suggest that caspase-5, or the dysregulated in fibrotic conditions including scleroderma. CCN2 pathways that regulate its expression, may represent novel therapeutic (CTGF) has been shown to play a key role in skin biology and fibrosis; targets in the treatment of IL-1b mediated pathology. however, the role of CCN1 (cyr61) in these processes are unclear. Disclosure statement: The authors have declared no conflicts of interest. Methods: We use fibroblast-specific CCN1 knockout mice (employing floxed CCN1 mice and a tamoxifen-dependent Cre recombinase expressed under the control of a fibroblast-specific collagen 1A2 promoter) and the bleomycin model of skin scleroderma to assess the potential role of CCN1 to skin connective tissue biology and fibrosis. Fibrosis is evaluated histologically using haematoxylin and eosin and BIOLOGY OF BONE CARTILAGE AND trichrome stains, and molecularly using a collagen ELISA to detect CONNECTIVE TISSUE insoluble and soluble collagen levels and real-time PCR analysis to assess messenger RNA (mRNA) expression. Results: Mice deleted postnatally for CCN1 showed reduced skin thickness 2 months post-deletion; CCN1-deficient mice also showed 237. THE INFLUENCE OF PERCENTAGE BODY FAT ON reduced levels of insoluble and soluble collagen protein (n ¼ 6, P < 0.05). BONE MINERAL DENSITY IN PATIENS WITH A BODY MASS When RNAs derived from mouse skin were analysed, collagen type I INDEX GREATER THAN 22 mRNA expression was unaffected by loss of CCN1; however, expression of mRNAs encoding collagen crosslinking/processing enzymes that are Andrew Blanshard1, Alex Oldroyd2 and Marwan Bukhari3 required for stability of collagen protein (PLOD2, LOX, P4H) were 1Rheumatology, Lancaster Medical School, 2Rheumatology, significantly reduced (n ¼ 6, P < 0.01). Mice deleted for CCN1 in Northwest Deanery and 3Rheumatology, Royal Lancaster Infirmary, fibroblasts were resistant to bleomycin-induced skin fibrosis as assessed Lancaster, UK histologically by skin thickness and trichrome stain (n ¼ 4, P < 0.05). 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Conclusion: Loss of CCN1 expression in fibroblasts results in blood, joints and skin. Recent mouse studies identified a central role resistance to bleomycin-induced skin fibrosis likely due to the for GM-CSF released by T helper 17 (Th17) cells in experimental involvement of CCN1 in promoting collagen stability. These results autoimmune encephalomyelitis. Here we investigate GM-CSF release are consistent with the hypothesis that an anti-CCN1 strategy may by Th17 cells in PsA. represent a novel therapeutic approach for fibrotic diseases such as Methods: Peripheral blood mononuclear cells (PBMCs) or SF derived scleroderma; anti-CCN1 strategies might work by promoting collagen from patients with PsA, or healthy donor (HD) PBMCs, were stimulated turnover and hence dissolution of scar tissue. with anti-CD3/anti-CD28 human T activator beads in the presence or Disclosure statement: A.L. has received research funding from the absence of recombinant IL-23. Supernatants were harvested and Canadian Institutes of Health Research and Scleroderma Society of analysed by ELISA for IL-17, IFNg or GM-CSF. Alternatively, PBMC or Ontario. The other author has declared no conflicts of interest. SF were activated with phorbol myristate acetate (PMA) and ionomycin, and CD4 T cells evaluated for the expression of Th17- associated cell surface markers including CCR6, CD161 and IL-23R. Cells were fixed, permeabilized and stained for IL-17A, IFNg and GM-CSF. CYTOKINES AND INFLAMMATION Results: As previously reported, GM-CSF was released by SF MCs derived from patients with PsA. GM-CSF release from PsA PBMCs was higher than that of HD PBMCs, whereas IFNg responses were higher in HDs. This reached significance when comparing the ratio of IFNg to GM-CSF, in that the ratio was 10.5 2.6 in PsA patients and 239. IL-1b REGULATES THE DECTIN-1 INDUCED CYTOKINE 35.1 8.2 in HD (P < 0.01). GM-CSF release was significantly down- PROFILE IN HUMAN DENDRITIC CELLS regulated (P < 0.0001) in pre-incubating PBMCs with IL-23, in contrast Matthew J. Elder1, Steven J. Webster1, David L. Williams2, to an increased production of IL-17 (P < 0.01). These data led to further John Stanley Hill Gaston1 and Jane C. Goodall1 evaluation of GM-CSF and IL-17 release by immunophenotyping. 50– 1Medicine, University of Cambridge, Cambridge, UK and 2Surgery 60% of CD4þCD3þGM-CSFþ cells co-expressed IFNg while 20–50% þ þ þ and Center for Inflammation, East Tennessee State University, of CD4 CD3 IL-17 cells produced GM-CSF. However, almost all þ þ þ Johnson City, TN, USA CD4 CD3 IL-17 cells express CCR6, approximately 50% of CD4þCD3þGM-CSFþ cells expressed this Th17-associated marker in Background: C-type lectin receptors including dectin-1 are pattern addition to CD161 and IL-23R. This suggested that a proportion of þ recognition receptors that recognize b-glucans on the surface of fungi, GM-CSF was indeed being released by a CD4 T cell subset other yeasts and bacteria. Immune responses to b-glucans have been than Th17; this will be further evaluated by cell sorting. Given that implicated both in a murine model of SpA (the SKG mouse) and AS chemokine receptors are down-modulated by PMA and ionomycin, þ patients have increased levels of antibodies to yeast. Dectin-1 CD4 T cells will be sorted according to the differential expression of stimulation initiates a plethora of immunological effector mechanisms CCR4, CCR6, CCR10 and CXCR3 prior to activation, to further from human dendritic cells (DCs), including phagocytosis and interrogate the subset(s) responsible for GM-CSF release. inflammatory cytokine secretion, required for protective immunity. b- Conclusion: IL-23 is a therapeutic target in PsA. We demonstrate that glucan presentation to DCs determines their capacity to generate GM-CSF release is elevated in patients with PsA, with a significant dectin-1-mediated inflammatory cytokines, and small particulate b- proportion of GM-CSF-producing cells exhibiting characteristics of þ glucans are thought to be poor activators of innate immunity. We Th17 cells. However, given that many GM-CSF cells also co-express investigated b-glucan induction of immune responses in humans DCs IFNg, and that GM-CSF release is down-modulated by IL-23, further and the role of IL-1b in their regulation. characterization of this putative therapeutic target is required. Methods: Human DCs were isolated from peripheral blood monocytes Disclosure statement: C.B.S. is supported by a NIHR Academic and differentiated with IL-4 and GM-CSF. DCs were stimulated with Clinical Lectureship. J.C.G. is supported by an Arthritis Research UK the dectin-1 agonists, curdlan (CUR) or b-1,3 glucan microparticles Senior Research Fellowship. The other author has declared no (MPs). conflicts of interest. Results: We show that large particulate b-glucans stimulate the secretion of the inflammatory T helper 17 (Th17)-priming cytokines IL- 1b, IL-6 and IL-23 from human DCs. In comparison, smaller b-glucans only stimulate negligible quantities of these cytokines, while stimulat- ing equivalent amounts of the cytokine TSLP and chemokine CCL22. EDUCATION Surprisingly, pro-IL-1b upregulation is unaffected by b-glucan size, suggesting inflammasome activation to process pro-IL-1b is missing. Inhibition of phagocytosis during small b-glucan stimulation induces IL-1b, IL-6 and IL-23 secretion from DCs, suggesting that prolonged dectin-1 signalling from the cell surface is required for their production. 241. USING CADAVERIC SPECIMENS TO INFORM In addition, we show that b-glucan induced IL-6, IL-23 and TSLP are LEARNING ABOUT MUSCULOSKELETAL ANATOMY AND regulated by IL-1b production. INTRA-ARTICULAR INJECTIONS Conclusion: These data demonstrate that different b-glucans induce Tim Blake1, Zoe Paskins2 and Andrew B. Hassell3 different cytokine profiles from human DCs. Furthermore, IL-1b 1Rheumatology, Haywood Hospital, High Lane, Burslem, Stoke-on- production regulates the composition of this inflammatory cytokine Trent, 2Arthritis Research UK Primary Care Centre, Primary Care profile. The DC-derived cytokine milieu is critically important in Sciences and 3School of Medicine, Keele University, Keele, UK orchestrating the nature of the adaptive immune responses to fungi. Since fungal infection and subsequent induction of Th17 responses is Background: The Joint Royal Colleges of Physicians Training Board implicated in the pathogenesis of SpA in the SKG mouse and Th17 curriculum for specialty training in rheumatology specifies that trainees responses are critical in human SpA, understanding mechanisms that should be able to identify surface anatomy of the musculoskeletal control this cytokine induction could suggest new therapies. system and demonstrate competence in performing common intra- Disclosure statement: The authors have declared no conflicts of articular injections. However, musculoskeletal anatomy is a relatively interest. neglected component of postgraduate learning in rheumatology, particularly in comparison with orthopaedics. The West Midlands 240. GM-CSF RELATIVE TO IFNg RELEASE IS HIGHER IN Service and Training Committee adopted an innovative training day for PATIENTS WITH PSA, AND GM-CSF IS ANTAGONISTICALLY specialist trainees using cadaveric specimens to teach anatomy and REGULATED BY IL-23 for practice of joint injection technique. This abstract reports an evaluation of this event. Carmel B. Stober1, Jane C. Goodall1 and John Stanley Hill Gaston1 Methods: A training session involving cadavers was established in 1Department of Medicine, Division of Rheumatology, University of order to facilitate learning about musculoskeletal anatomy and intra- Cambridge, Cambridge, UK articular injection techniques. This involved a half-day demonstration and practical aimed at specialist trainees in rheumatology. Data were Background: The spondylarthritides, AS, PsA and enteropathic collected retrospectively via a web-based tool; an electronic ques- arthritis, cause chronic inflammation of peripheral and axial joints, tionnaire was sent to specialist trainees in the West Midlands region in eyes, skin, ileum and colon. Genetic studies reveal common candidate September 2014. Questions concerned the current opportunities for genes for AS, PsA, and Crohn’s disease, including IL23R, IL12B, anatomy and joint injection training, comparative levels of confidence STAT3 and CARD9, all associated with IL-23 signalling. We have before and after the training session, overall satisfaction of the session recently shown elevated frequencies of CD4þIL-17þ cells in PsA in and projections about how such a training day could be enhanced. i144 Thursday 30 April 2015 POSTER VIEWING III

Descriptive statistical data analysis was performed using Microsoft Disclosure statement: All authors are employees of the National Excel. Rheumatoid Arthritis Society (NRAS) and did not personally receive Results: The response rate was 87.5% (14/16). All respondents found funds for the project. that the cadaveric specimens provided a worthwhile and effective way to learn about the anatomy of joints and the musculoskeletal system. Overall, the learning experiences were better or significantly better 243. DEVELOPING AN INSTRUCTIONAL EXERCISE DVD FOR than previous joint injection training, with respect to efficiency of RHEUMATOID ARTHRITIS PATIENTS learning (13/14, 93%), enjoyment (13/14, 93%), acquisition of technical 1 1 1 skills (12/14, 86%), demonstration (12/14, 86%), social interaction (11/ Rachel E. Cook , Rohan G. Mathew , Thomas D. O’Brien , Robert Caine2, Jeremy G. Jones1,2, Yasmeen Ahmad2 and Andrew 14, 79%) and personal engagement (9/14, 64%).One respondent 1 reported an indifferent view on enjoyment of the session, although no B. Lemmey 1School of Sport, Health & Exercise Sciences, Bangor University, negative comments were volunteered. Free text responses revealed 2 that cadaveric specimens were particularly useful for practice of Bangor and Peter Maddison Rheumatology Centre, BCUHB, intricate injections such as the carpal tunnel and first carpometacarpal Llandudno Hospital, Llandudno, UK joints. Trainees favoured the collaboration of colleagues and demon- strators on performing injections in an unthreatening environment, so Background: RA is characterized by adverse changes in body ensuring that practice is fair and equal among trainees and not composition (increased fat mass, decreased muscle mass), substan- dependent on local opportunities and teaching. Self-reported con- tially reduced physical function and increased risk of cardiovascular fidence increased by a mean of 15.7% for identifying surface anatomy disease, metabolic syndrome, type II diabetes, osteoporosis and (70% to 85.7%) and by 22.2% for performing intra-articular injections depression. Regular exercise benefits each of these conditions, and is (67.9% to 90.1%) following the training session. Thirteen (13/14, 93%) safe for RA patients. Despite this, most RA patients do not regularly subjects were keen to see a similar training session to become exercise; in part due to lack of knowledge about the benefits of incorporated into the regular rheumatology trainee programme. exercise, uncertainty regarding how to exercise and unfounded fears Conclusion: This study draws our attention to the often neglected of exacerbating disease activity, pain and fatigue. area of postgraduate anatomy learning in the rheumatology training Methods: To educate RA patients about exercise, and hopefully programme. There is a call for rheumatology specialist trainees to provide motivation for them to commit to exercise training, Bangor receive more interactive and engaging anatomy learning. The authors University and Betsi Cadwaladr University Health Board, using a propose that more cadaver-style teaching is utilized and embraced by patient-centred approach which investigated patient preferences, training boards. have developed an instructional exercise DVD. Disclosure statement: The authors have declared no conflicts of Results: Focus group participants (of varying age, gender, disease interest. duration and current physical activity levels), were recruited from RA patients groups in North Wales (Arthritis Care UK, Rheumatoid Exercise Programmes and RA patient education sessions). These 242. RA AWARENESS WEEK: INCREASING THE MEDIA sessions elicited from the patients what information they wanted from PROFILE OF RHEUMATOID ARTHRITIS the DVD regarding how to exercise, the benefits and safety of exercise,

1 1 2 and gym vs home-based exercise programmes. These focus group Daniela K. Boyd-Waters , Ruth Grosart and Oliver Hoare discussions were audio-recorded and transcribed, and transcripts 1Media & Communications, National Rheumatoid Arthritis Society 2 were studied by the academic and clinical team (i.e. exercise and Fundraising, National Rheumatoid Arthritis Society, Berkshire, physiologists, rheumatologists, physiotherapists and occupational UK therapists). The patient feedback highlighted the need for more education on the health and functional benefits of exercise, how to Background: In 2013, we surveyed our members to find out what we exercise and the need to dispel myths regarding the safety of exercise. should highlight in our second national awareness campaign and we Patients felt that having this information in a recorded format (i.e. DVD) were inundated with requests to raise awareness that RA is an invisible was beneficial as they find extensive verbal information difficult to disease. They told us that the pain, fatigue and stiffness they live with assimilate and retain. The majority also wanted a follow-along visual cannot be seen by people around them and that family/friends didn’t demonstration exercise section. Consequently, the DVD consists of fully understand what they live with on a daily basis. They also felt that three sections. The first has contributions from an academic RA isn’t talked about enough in the media and that people have researcher, rheumatologist, and physiotherapist on the benefits and misconceptions about the disease. Thus, our theme for our second RA safety of exercise for RA patients, advises patients about accessing Awareness Week (16–22 June 2014) became The Invisible Disease. exercise facilities in their local community (including at home) and Our key message was Let’s be vocal so RA is visible. patient testimonies on their perceptions of the benefits of exercise as a Methods: To improve on 2013’s activity, we knew involvement from source of motivation to others. The second section is gym-based, and our members, supporters and followers on social media was key. informs patients about training principles and shows them how to use Again, we hosted a thunderclap (a crowdspeaking platform that rallies aerobic and resistance machines (as many patients wish to use gyms people together to spread a message) which reached 200 000 people but lack the necessary confidence to do so). The third section consists (120 000 more than in 2013) and used the hashtag #LookDeeper to of instruction on how to exercise at home (the preference of many generate discussions. We ensured that there were plenty of ways to patients), and also includes a home-based exercise class demonstra- get involved covering all abilities. We held our first national fundraising tion. Training demonstrations are led by a physiotherapist with patients event, a walk entitled The RAmble. Our report, Invisible Disease: RA performing the exercises (in line with patient feedback) and aims at and Chronic Fatigue 2014, launched the week and was responsible for increasing patient confidence in their ability to exercise. a great deal of national coverage, with fundraisers and groups Conclusion: This DVD will be given to all BCUHB West RA patients. securing considerable local coverage. Funding: The project was funded by a patient’s bequest. Results: The week was a remarkable improvement on 2013, especially Disclosure statement: The authors have declared no conflicts of in terms of media coverage. We gained eight pieces of national interest. coverage and 80 pieces of radio and local coverage. An interview with Jeremy Vine on BBC Radio 2 with Ailsa Bosworth, the National Rheumatoid Arthritis Society chief executive officer, to 15 million 244. PEER-TO-PEER INNOVATIVE ONLINE TRAINING listeners, was a highlight. The findings of the Fatigue Report helped us to gain national coverage in the Daily Mail, The Express, The Star and Kim Fitchett1, Gill Weedon1, Clare Jacklin1 and Julie Murrell2 the Mail on Sunday. Outstanding local coverage was obtained through 1External Affairs, National Rheumatoid Arthritis Society, Maidenhead supporter activity. We also invested in advertising in The Metro and and 2Counselling Service, Bisham, UK advertised The RAmble on Free Radio, which had some success. In addition, we succeeded in gaining celebrity and political support, with Background: The National Rheumatoid Arthritis Society (NRAS) peer- quotes from Claire King, Jenny Agutter, Jo Whiley, Craig Revel Horwood, to-peer telephone support service was established in 2003 and has over Hazel O’Connor, David Cameron, Nick Clegg and Ed Milliband. We also 80 telephone support volunteers. To ensure that both the volunteer and had social media support from Karen Millen and Hilary Jones. the recipient of the support call have access to high quality support, it is Conclusion: Feedback was extremely encouraging. Celebrity engage- important for new and existing volunteers to have access to up to date ment really helped people to interact with our social media channels training. Not only is knowledge of RA and NRAS services important for with Claire King’s quote achieving 762 likes and reaching 34 448 the volunteer to be aware of but they also need specific skills and people. The RAmble will now take place annually. The awareness attributes to be able to be empathic and supportive. With limited week for next year is now in planning the stage. resources and funding some new applicants were left waiting too long Funding: Supported by Pfizer, MSD and BMS, who had no influence for face to face training which could mean they lost interest. The need for over the content of these materials. distance learning was the obvious solution which would enable POSTER VIEWING III Thursday 30 April 2015 i145

volunteers to be appropriately trained and assessed without having to 246. DEVELOPMENT OF A MODULAR-BASED ULTRASOUND travel to training, thus incurring expense and time out of work etc. TRAINING PROGRAMME FOR RHEUMATOLOGISTS AND Methods: NRAS collaborated with a professional counsellor to ALLIED HEALTH PROFESSIONALS IN WALES develop a group training programme. NRAS members volunteered to 1 2 3 4 be filmed participating in the training session. The topics covered Emyr Humphreys , Vun Lim , Alex Kraus , Ernest Choy and Sarang Chitale5 within the training are listening skills; interpreting feelings; establishing 1 a rapport; managing a conversation; helpful questions and feeding Rheumatology, Bwrdd Iechyd Prifysgol Cwm Taf Health Board, Merthyr Tudful, 2Rheumatology, Bwrdd Iechyd Prifysgol Betsi Cadwaladr back to demonstrate understanding. A workbook accompanies the 3 filmed training available online or on DVD. The NRAS team assesses University Health Board, Wrecsam/Wrexham, Rheumatology, Bwrdd Iechyd Prifysgol Betsi Cadwaladr University Health Board, Bangor, the volunteer’s completed workbook and conducts a follow-up phone 4 call with the volunteer using scripted questions to further measure their Rheumatology, Bwrdd Iechyd Prifysgol Caerdydd a’r Fro/Cardiff & Vale 5 understanding of the course’s key learnings. Following the volunteer’s University Health Board, Caerdydd / Cardiff and Rheumatology, Peter first completed peer-to-peer support call a further assessment is Maddison Rheumatology Centre, Bwrdd Iechyd Prifysgol Betsi carried out and they are called by NRAS staff, as is the person who Cadwaladr University Health Board, Llandudno, UK received the support call. It is following this final assessment that the volunteer is confirmed in their role. Background: US is increasingly used by rheumatologists, yet Results: New telephone support volunteers have now completed the training and are already making support calls as required. All existing opportunities for formal accredited training are scarce. We report the volunteers are requested to complete the training as a refresher establishment of the Welsh Rheumatology US Special Interest Group course. As a result, the quality of this NRAS service will be vastly (SIG). Its aims are to support US training and research for improved and NRAS are actively recruiting more volunteers to address rheumatologists and allied health professionals (AHPs). the shortfall in certain topic areas that callers request. Methods: A survey of US experience, availability of a machine and Conclusion: Feedback from those whom have completed the course mentorship was conducted among rheumatologists in Wales. As a has been very positive as they feel more appreciated and skilled in result, the Welsh US SIG core steering committee (with representation their role. The accessibility of the course also has enabled more active from rheumatologists, specialist registrars, radiologists, sonographers recruiting of volunteers and people find the training less cumbersome and AHPs) was established to drive the US educational agenda. In to complete. Increased numbers is important but the improved quality Wales, Two centres in the north and three in the south with of the support being offered is of great value to the society’s funders rheumatologists and musculoskeletal (MSK) radiologists delivering and gives assurances to health care professionals who signpost US training were identified. US trainees were asked to maintain a patients to this NRAS service. logbook of scans performed. In addition, twice a year an all-Wales Disclosure statement: K.F. has received research funding from masterclass would be conducted based on US modules and would Pfizer. All other authors have declared no conflicts of interest. include competency assessments by external examiners. An annual train the trainer session will be held in addition. Two masterclasses were held this year: the first module was on hands and wrists anatomy, 245. THE REMISSION MISSION: UNDERSTANDING the second on hands and wrists pathology and ankle and feet anatomy REMISSION IN RHEUMATOID ARTHRITIS FROM THE and pathology. US physics and instrumentation modules were PATIENT’S PERSPECTIVE included in both. Feedback based on Likert scale (1 ¼ poor to 5 ¼ excellent) was collected. 1 2 Ruth Grosart and Tracey Hancock Results: Of the 15 rheumatologists (11 consultants and 4 trainees) 1 2 Media & Communications and Development, National Rheumatoid completing the survey, 8 had basic/intermediate US experience, Arthritis Society, Maidenhead, UK whereas 7 reported no experience. Only four had US performed within the rheumatology department. Eight had a local mentor for US training. Background: The National Rheumatoid Arthritis Society (NRAS) is Eight specialist trainees attended the first, whereas 17 (five con- committed to empowering those affected by RA, and improving sultants, one staff grade, eight specialist trainees, two physiothera- understanding around disease management. In 2013 we conducted a pists and one podiatrist) the second masterclass. The individual survey entitled ‘What does remission mean to you?’ to uncover the views session feedback from these is shown in Table 1. of people with RA, looking at the term remission, what it means to them Conclusion: A paucity of local US training and mentorship was and their understanding of the DAS for 28 joints (DAS28). Over 1100 identified in Wales leading to the development of the Welsh US SIG people took part, indicating the subject is important for those with this that included MSK radiologists. Delivery of modular US training at the life-changing condition. We decided to develop the project further by all-Wales level has been well received with a positive feedback. In creating a website for people with RA to share their idea of remission, addition, ongoing local mentorship with maintenance of logbooks and thereby raising awareness of the need for improved disease manage- annual train the trainers US courses will ensure high quality ment and highlighting that remission is not just a clinical definition. rheumatology US training in Wales. Methods: We filmed five videos of patients talking about remission and Disclosure statement: E.H. was provided with demonstration US DAS28. We also set up video booths at three patient and healthcare machines by Sonosite on the days of Wales US Special Interest Group professional events to record what remission meant to the visitors. We Masterclasses. S.C. received funding from AbbVie for purchasing an then worked with our website developers to create a photo wall called US machine. All other authors have declared no conflicts of interest. the Remission Mission where these videos could be showcased and giving users the opportunity to upload a photograph and message of a what remission means to them. We asked celebrities connected with RA 246 TABLE 1. Feedback from all-Wales US Masterclasses 1 and 2 to take part, helping us reach a wider audience. The site was designed to Feedback from Feedback from reflect the DAS28 materials and our website. At our annual conference, Masterclass 1 Masterclass 2 we collected photos and messages from attendees to populate the site (April 2014) (September 2014) before its launch in October 2014, just before World Arthritis Day. attendees (n ¼ 8) attendees (n ¼ 11) Results: People with RA, their family, friends and healthcare US physics & instrumentation 4.6 4.5 professionals are still contributing to the Remission Mission, and the Anatomy: hands & wrists 4.6 4.55 engagement has already been encouraging. In the first month alone, Anatomy: ankle & feet — 4.3 Scanning techniques 4.7 — there were 2500 visits to the site with 150 people taking part in the call Practical session 4.87 4.27 to action. The majority of users so far have been in the 18–35 years age US quiz — 4.18 group, with an equal split between men and women taking part. We a ¼ ¼ expect participation to increase as we continue to promote the On a Likert scale of 1–5, where 1 poor and 5 excellent. campaign through our social media channels and website, with the goal of 1000 people joining the mission by World Arthritis Day 2015. Conclusion: The ‘What does remission mean to you?’ developing into the Remission Mission campaign highlights the impact of RA on the 247. DEVELOPMENT OF A TRAINING MODULE FOR lives of those with the disease as well as their family and friends, and RHEUMATOLOGY HEALTH PROFESSIONALS ON THE TOPIC increases understanding that remission means something different for OF HAVING SENSITIVE CONVERSATIONS WITH PATIENTS each individual. It encourages them to improve communication with ABOUT RELATIONSHIPS AND SEXUALITY their medical team in order to achieve better outcomes in the management of their condition. NRAS and Roche will now review Clare B. Jacklin1, Sarah Collins2, Ailsa Bosworth3 and Rod Hughes4 the materials on DAS and develop our information on remission. 1External Affairs, NRAS, Maidenhead, 2Independent, Own Business, Funding: This work was funded by Roche & Chugai. Gloucestershire, 3NRAS, Maidenhead and 4Rheumatology, St Disclosure statement: The authors have declared no conflicts of interest. Peter’s Hospital, Chertsey, UK i146 Thursday 30 April 2015 POSTER VIEWING III

via the regional trainee representative network, and to educational Background: The National Rheumatoid Arthritis Society (NRAS) 2013 supervisors and ARCP panel members via the SAC network. Having survey and subsequent publication on the impact of RA on patients’ been endorsed by the Joint Royal Colleges of Physicians Training emotional health, relationships and sexuality highlighted that rheuma- Board (JRCPTB), it was also made available online via the official tology health professionals felt they had little or no skills training to be website (http://www.jrcptb.org.uk/trainingandcert/Documents/2014% able to feel comfortable to open the door to discuss sensitive, 20JRCPTB%20Pre-ARCP%20checklist.pdf). In order to assess the emotional and sexual issues with their patients in an empathic and usefulness of this tool and ways of improving it, an online survey was helpful way conducted to explore rheumatology supervisors’ and trainees’ views Methods: A subsequent NRAS survey of rheumatology nurses and on the Pre-ARCP checklist. allied health professionals revealed that many often avoided opening Results: The survey ran for 6 months, with a total of 65 responses from 12 such conversations as they felt they could offer few if any solutions or deaneries. 37(57%) respondents were trainees and the remaining trainers did not know enough about available support to signpost patients to [22 (34%) educational/clinical supervisors, 14 (22%) ARCP panel for therapy and guidance. The lack of availability of talking therapies in members, and 3(5%) training programme directors, with most trainers RA is well established. NRAS worked with the psychotherapeutic having >1 roles]. 54 (83%) of the respondents were aware of the Pre- counsellor (who has RA herself) who authored the NRAS Emotions, ARCP checklist and 47 (72%) used it in preparation for the ARCP. Of the Relationships and Sexuality guide, to pilot an interactive 1-day training 47 respondents who used it, 43 (91%) found it helpful; 94% of all for rheumatology health professionals. Taking the results from the respondents would use it in future. Most respondents found out about the pre-course questionnaires, it was clear that HCPs wanted to be given checklist via the trainee representatives forums (32%) or TPDs (31%) and guidance around what they could and could not say to patients to 18% via deanery or JRCPTB communication. 88% preferred to receive maintain their professionalism while showing empathy and humanity. information about future updates via email. Qualitative comments were The day was structured with a mixture of presentations, role plays and very favourable and highlighted areas needing ongoing updates. discussions. Topics included impact of rheumatology drugs on libido, Conclusion: Trainees and supervisors can feel overwhelmed by fertility, contraception and sexual function; scenario role plays taking frequent curriculum changes and new assessment formats. Having an turns at being the patient and the health professional; presentations annually updated tool to summarize and guide the preparation leading and video clips about empathy and ‘wearing others’ shoes’; under- to the annual appraisal has been welcomed and found to be useful by standing sexual anatomy, sexual problems arising from having RA, and both trainees and trainers. The Pre-ARCP checklist helps simplify the suggested ways to open discussion on these issues process of collecting and presenting the evidence required, as Results: 14 nurses, physiotherapists, occupational therapists and reflected by the fact this Pre-ARCP checklist has now been endorsed researchers attended the pilot session, although many more wanted to by JRCPTB to be used across all medical specialties, thus emphasiz- but could not be released from their duties to attend. Of the 13 ing its educational utility. feedback responses obtained, 69% said they would be extremely Disclosure statement: The authors have declared no conflicts of likely or very likely change their clinical practice as a consequence of interest. what they had learned during the training. Many attendees commented on not having previously thought, or had any knowledge of, the impact of certain drug therapies on patients’ sex lives. 100% of attendees said 249. SURVEY OF JOINT INJECTION PROCEDURE IN THE the ‘putting yourself in the patient’s shoes’ role plays were incredibly YORKSHIRE AND HUMBER AREA thought-provoking and some stated that these were the highlight of the course. Anetha Sabanathan1 and Lisa Dunkley2 Conclusion: Taking into account the feedback from delegates the 1Hull Institute of Learning and Simulation, Hull Royal Infirmary, Hull pilot has been modified slightly to allow more time to be spent on the and 2Rheumatology, Sheffield Teaching Hospital NHS Foundation areas of most value to the professionals and will now include more Trust, Sheffield, UK real-life patient experiences. The health professionals all felt this was a unique, unprecedented and much-needed training resource that Background: While developing a simulation joint injection course for should be made available to all who work with people with RA and rheumatology trainees, the question was raised regarding what should other long-term conditions we be telling our trainees regarding practice? To look at this, we Acknowledgement: The NRAS received an unrestricted grant from performed a new survey in the Yorkshire and Humber region (UK). Roche to support development of the programme and the UCB hosted Methods: An electronic survey was sent out to the Yorkshire and the pilot at their offices, but no individual received direct funding. Humber rheumatology consultants and registrars. Disclosure statement: The authors have declared no conflicts of Results: There were 33 responses. 96% used verbal consent. When interest. counselling patients, 92% would discuss failure of procedure, cosmetic risks and infection risk. However, when discussing infection risk, only 40% would use a numerical risk factor. 80% would discuss 248. THE PRE-ANNUAL REVIEW OF COMPETENCE bleeding risk, with 56% discussing the possibility of failure of the PROGRESSION CHECKLIST: DEMYSTIFYING THE ANNUAL procedure itself. Of patients on warfarin, 57% would proceed with REVIEW OF COMPETENCE PROGRESSION PREPARATION procedure if international normalized ratio (INR) <2.5, 20% if INR <3, FOR RHEUMATOLOGY 13% would omit warfarin and proceed if INR <2, 3% said they would not proceed at all and 3% would continue regardless. 66% use alcohol 1 2 3 Eleana Ntatsaki , Nicola Tugnet , Kavitha Nadesalingam and wipe to clean the skin, with 63% using chlorhexidine. 31% always 4 Tom Lawson used ethyl chloride, with 19% never using. 52% of our survey would 1 Rheumatology, Peterborough City Hospital, Peterborough, wait 3 months between injections, 33% would wait longer and 26% 2 Rheumatology, Walsall Healthcare NHS Trust, Walsall, would wait 2 months or less. 41% would inject two joints at one sitting, 3Rheumatology, Bradford Teaching Hospitals NHS Foundation Trust while 34% would inject more than three joints in one sitting. The most and Rheumatology Department, St Lukes Hospital, Bradford and commonly used steroid for joint injection was methylprednisolone 4Rheumatology, Princess of Wales Hospital/Neath Port Talbot acetate, followed by triamcinolone acetonide for the larger joints and Hospital, Port Talbot, UK hydrocortisone acetate for the small joints. Doses of methylpredniso- lone acetate ranged from 40 mg to 80 mg (median 80 mg) for the knee, Background: The Annual Review of Competence Progression (ARCP) 20 mg to 80 mg (median 40 mg) for the ankle, 40 mg to 80 mg (median is the formal method by which a trainee’s progression is monitored and 40 mg) for the shoulder, 20 mg to 40 mg (median 40 mg) for the elbow recorded. The evidence reviewed by ARCP panels is collected in the joint, 20 mg to 40 mg (median 40 mg) for the wrist, 5 mg to 40 mg trainee’s e-Portfolio. ARCP Decision Aids, revised by the Specialty (median 10 mg) for the MCP, proximal interphalangeal (PIP) and distal Advisory Committees (SAC), define the targets to be achieved for a interphalangeal (DIP) joints (MCP/PIP/DIP), and 10 mg to 40 mg satisfactory ARCP outcome at the end of each training year. However, (median 20 mg) for carpal tunnel. Doses of triamcinolone acetonide given the constant changes in the curriculae and the complexity of the ranged from 40 mg to 80 mg (median 80 mg) for the knee, 20 mg to e-portfolio, clinically competent trainees may fail to achieve a 40 mg (median 40 mg) for the ankle, 20 mg to 40 mg (median 40 mg) for satisfactory outcome due to lack of awareness of the training the elbow, 20 mg to 40 mg (median 30 mg) for the wrist, and 5 mg to objectives or evidence required. There is therefore a need for an aid- 10 mg (median 7.5 mg) for the MCP/PIP/DIP, with a dose of 10 mg memoire when preparing for the ARCP in order to navigate through the (median 10 mg) for the carpal tunnel. Hydrocortisone acetate doses e-portfolio and meet the requirements. were 25 mg for the elbow and ranged from 20 mg to 25 mg (median Methods: We reviewed the guidance for ARCP and collated the 25 mg) for the wrist, 5 mg to 25 mg (median 12.5 mg) for the MCP/PIP/ necessary steps prior to an ARCP appraisal on a short document. This DIP, and 10 mg to 25 mg (median 25 mg) for the carpal tunnel. 12% of Pre-ARCP checklist reflected the changes to specialty training our survey would use local anaesthetic for infiltration, 8% would never assessment that came into effect in August 2014. The document use a local anaesthetic and 27% would always mix the steroid with the was approved by the rheumatology SAC and disseminated to trainees local anaesthetic for injections. 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Conclusion: A consensus regarding injection practice has not been 251. A TWO-MINUTE SITTING EXERCISE REGIME TO reached. In particular issues around counselling, patients on warfarin, EDUCATE AND ENCOURAGE SEDENTARY PATIENTS TO injection doses, local anaesthetic use and the number of joints injected EXERCISE at one time, remains variable. More research into injection practice is Daisy Stevens1, Lyn Williamson1, David Collins1 and Elizabeth Price1 needed to help produce consensus on future practice and teaching. 1 Disclosure statement: The authors have declared no conflicts of Rheumatology, Great Western Hospital, Swindon, UK interest. Background: Sedentary lifestyle is associated with increased morbid- ity and mortality. Motivating people to exercise is important, but 250. CAN YOU SIMULATE GOUT TEACHING? difficult. Rheumatology patients may have problems with pain and Anetha Sabanathan1, Makani Purva2, Philip Helliwell3, mobility which prevent them walking. Others are simply unwilling to Thangiaruban Thurairajah4, Xavier Fernando1 and Anoop Prakash1 start exercise due to lack of time, laziness, ignorance about correct 1Hull Institute of Learning and Simulation, Hull Royal Infirmary, Hull, exercises and fear of pain. 2Medical Education, Hull Royal Infirmary, Hull, 3Leeds Institute of Methods: We developed a patient education leaflet containing a Rheumatic and Musculoskeletal Medicine, University of Leeds, Two-Minute Stretch programme of eight exercises chosen by Leeds, 4GP VTS, Mid Yorkshire Hospitals NHS Trust, Dewsbury, UK multidisciplinary consensus. The exercises were designed to be used while sitting at home or work, while travelling, in outpatient Background: Simulation has been highlighted as a vital part of waiting areas and by wheelchair and bedbound patients. The building a safer healthcare system. However evidence that simulation exercises target both peripheral and axial muscle groups, with is more effective than traditional teaching is still poor. There is very focus on good posture and deep breathing. Exercises included: little simulation research on the teaching of non-practical skills and its shoulder rolls; arm extensions; leg raises; ankle and calf stretches; use in rheumatology. Gout admissions to hospital are rising. Doctors side and back stretches and reaching and twisting movements. should therefore have knowledge in the management of gout to Information was presented in basic sentences (Flesch reading ease improve patient care. Our objective was to compare effectiveness of score of 95.7/100), supported by simple diagrams. Rheumatology simulation methodology to traditional teaching methods in the area of outpatients, staff and volunteers trialled the exercises by following the gout management. instruction leaflet. We collected data on gender, age, leaflet read- Methods: This is a multicentre study involving general practitioner trainees ability, exercise achievability, feelings after the trial and whether within the Yorkshire and Humber region (UK). Trainees from each site will patients would do the exercises at home. either have a traditional lecture or simulation teaching on gout. Pre- and Results: 75 people completed the questionnaire: 49 in the patient post-teaching questionnaires accessing feedback and satisfaction/con- group and 26 in the staff/volunteer group. There were 18 male and 32 fidence scores, and standardized questions related to gout (based on female, with 25 unspecified. The age range was 20–79 years, and there current British Society for Rheumatology guidelines) will be performed was 1 patient aged 11–20 years, 17 aged 21–30 years, 2 aged 31–40 immediately pre- and post-completion of teaching sessions and at one years, 5 aged 41–50 years, 5 aged 51–60 years, 5 aged 61–70 years, month. The primary outcome measures will be an improvement in pre- and 4 aged 71–80 years, with 36 of unspecified age. All patients said and post-test scores, with secondary outcomes looking at retention at 1- they understood the instructions on the leaflet. 68 of 75 (91%) month and confidence levels before and after training. answered that they could perform all exercises- >75% of people from Results: Currently, 35 trainees have been recruited from one area. In the each age group. All participants younger than 51 years could do all of simulation group (n ¼ 20), test scores improved from a range of 5–14 the exercises, and three of the 11 (27%) people older than 51 years (median 10, mean 10.5). Overall, there was an increase in confidence were unable to do one or more of the exercises. 40 of the 49 patients levels in the simulation group (Table 1), with significant improvement in (82%) said they would do the exercises daily at home. After doing the confidence to treat gout acutely (4.05 to 4.95, P ¼ 0.01). In the lecture exercises, 161 out of 168 (95%) of emotional responses were positive: group (n ¼ 15) test scores improved from a range of 2–12 (median 9, 25 were happy, 19 were awake, 29 were relaxed, 3 had less pain and 4 mean 10.5). There was an overall increase in confidence levels in this felt their condition was improving. Four out of 84 (5%) gave negative group (Table 1), with significant improvement in confidence to under- responses: two were in more pain and two were tired. 56 out of 70 stand cause and risk factors for gout went from a mean of 4–5.13 (80%) felt no new pain. 9 out of 49 (18%) said they would not do the (P ¼ 0.03), to understand reasons for gout treatment (3.87 to 5.4, programme at home: reasons given were laziness (3/9) and pain (3/9); P ¼ 0.01) and overall confidence to treat gout (4 to 5.47, P ¼ 0.03). the remaining 3 wrote they were too busy, already doing other exercise Conclusion: Simulation can be used to successfully teach non- or not disciplined enough. practical skills. We have seen a similar immediate improvement in test Conclusion: We present a Two-Minute Stretch sitting exercise scores in both groups. Previous literature has shown mixed results in programme designed to help rheumatology outpatients start to exercise. test score improvement, with some showing a small improvement and The programme is safe, achievable and supported by this simple leaflet: others showing no significant difference between teaching methods. http://www.gwh.nhs.uk/media/170803/sitting_exercises_level_1_leaflet. We found an overall improvement in both groups in confidence levels, pdf though this appears to be more significant in the lecture group. Disclosure statement: The authors have declared no conflicts of Disclosure statement: The authors have declared no conflicts of interest. interest.

250 TABLE 1. Confidence scores before and after training Confidence in your overall ability: Mean Mean P-value Mean Mean P-value confidence confidence confidence confidence scores scores scores scores pre-simulation post-simulation pre-lecture post-lecture To understand cause of and risk factors for gout 3.45 4.85 0.00 4.00 5.13 0.03 To identify potential differentials 3.65 4.90 0.00 4.33 4.67 0.36 To treat gout acutely 4.05 4.95 0.01 4.60 5.47 - To treat gout long term 3.85 4.80 0.00 4.14 5.33 0.13 To monitor gout treatment 3.30 4.95 0.00 3.27 5.07 0.00 To understand reasons for gout treatment 3.40 4.75 0.00 3.87 5.40 0.01 To understand potential contraindications/ 3.10 4.75 0.00 3.27 5.00 0.00 cautions to certain treatment used for acute/ chronic gout management To understand when the need to refer to specialist 3.10 4.90 0.00 3.00 5.87 0.00 To treat and manage gout 3.53 4.90 0.00 4.00 5.47 0.03 i148 Thursday 30 April 2015 POSTER VIEWING III

gene. It has thus been speculated that they are likely to regulate gene expression, and it has recently been shown that the majority of the GENETICS associated regions lie in gene enhancer elements. Associated loci are often annotated with the nearest, biologically plausible gene name; however, this may be misleading as enhancers are known to be able to act over long distances, often skipping the nearest gene. Here we 252. CHROMATIN MARKS MAPPING TO JUVENILE develop a modified HiC method to interrogate all promoters likely to be IDIOPATHIC ARTHRITIS ASSOCIATED GENOMIC REGIONS involved in RA to provide empirical evidence as to which enhancers IDENTIFY CD4 AND REGULATORY T CELLS AS CRITICAL they physically interact with and whether those enhancers contain a CELL TYPES IN JIA variant associated with RA. Methods: RA loci were defined as SNPs with r2 > 0.8 with the lead 1 1 2 3 Joanna Cobb , Anne Hinks , Miranda C. Marion , Marc Sudman , SNP, identified by genome-wide association studies. We then defined 1 4 5 John Bowes , John Bohnsack , Lucy R. Wedderburn , Johannes all promoters within 500 kb of RA-associated SNPs. Custom oligonu- 6 2 7 P. Haas , Carl D. Langefeld , Sampath Prahalad , Suzan cleotide baits complimentary to all promoter regions were designed 3 1 D. Thompson and Wendy Thomson and synthesized (n ¼ 5595; Agilent). A HiC library prepared from Jurkat 1 Arthritis Research UK Centre for Genetics & Genomics, University of cells (n ¼ 60 million) was enriched with the custom baits. The resulting 2 Manchester, Manchester, UK, Department of Biostatistical library was sequenced on one lane of an Illumina HiSeq. We then Sciences, Wake Forest University School of Medicine, Winston- applied novel statistical algorithms to determine which promoter– Salem, NC, 3Division of Rheumatology, Cincinnati Children’s Hospital enhancer interactions are observed more often than by chance. Medical Center, Cincinnati, OH, 4Pediatric Rheumatology, University Results: Analysis of the first HiC library has revealed over 145 000 of Utah Health Sciences Center, Salt Lake City, UT, USA, 5Institute of interactions with promoter sequences (mean 26 interactions per Child Health, University College London, London, UK, 6German promoter, range 0–185). These interactions were from 57 000 Centre for Paediatric and Adolescent Rheumatology, Garmisch- enhancers of which the 272 containing 743 RA-associated SNPs, Partenkirchen, Germany and 7Department of , Emory interacted with 474 promoters. This analysis has reduced the number University School of Medicine, Atlanta, GA, USA of potential RA promoters from 5595 to 474 and has identified 743 SNPs from 2190 with potential enhancer function. We are examining Background: JIA is the most common arthritic disease of childhood each RA locus in turn to analyse the evidence for the mechanism of and is caused by a combination of genes and environment. In the last interaction of disease-associated SNPs with gene regulation and have few years, great advances have been made in dissecting the genetic already identified several examples of long range promoter enhancer basis of JIA, with 17 susceptibility regions now confirmed. However, interactions. For example, the association signal at the IRF8 locus on little is known about which cell types these genes are expressed in, chromosome 16 is 50 kb from the nearest gene (IRF8), and we now making functional characterization of genetic associations in JIA have evidence of a physical interaction with the IRF8 gene promoter. challenging. One way to inform cell-type specificity is to use epigenetic Conclusion: Our preliminary findings indicate that the relationship of chromatin marks, such as H3K4me4 which act as a proxy for enhancer to promoter is likely to be complex, with promoters regulatory elements and show tissue specificity. An enrichment of interacting with a number of enhancers and, likewise, enhancers JIA associated genetic variants overlapping these H3K4me3 marks interacting with a number of promoters. Our findings suggest that this within particular cell types gives insight into the critical cell types for methodology will have the capability to reduce the number of JIA. The aim of this work was to use genetic associations identified in a associated SNPs that interact with a promoter and are therefore cohort of JIA patients with the three most common subtypes of JIA likely to be causal, as well as definitively linking an enhancer containing (persistent oligoarticular, extended oligoarticular and RF-negative an associated SNP, to a gene promoter. polyarticular arthritis) to gain insight into the critical cell types when Disclosure statement: The authors have declared no conflicts of undertaking fine-mapping studies in JIA. interest. Methods: JIA susceptibility single nucleotide polymorphisms (SNPs) were identified from a previously published fine-mapping dataset obtained from analysis of the custom-designed Illumina ImmunoChip 254. ASSOCIATION OF CHEMOKINE CXC LIGAND 12 GENE in 2816 JIA cases and 13 056 controls from the UK, USA and Germany. POLYMORPHISM (RS1746048) WITH CARDIOVASCULAR Phenotypic cell-type specificity of these SNPs was assessed using MORTALITY IN PATIENTS WITH RHEUMATOID ARTHRITIS: publically available H3K4me3 chromatin mark data from 34 cell or RESULTS FROM THE NORFOLK ARTHRITIS REGISTER tissue types. In an approach similar to that recently published for Ra, Ibrahim Ibrahim1, Sebastien Viatte1, Jennifer Humphreys1, the enrichment of JIA associated SNPs was calculated by first utilizing Ibtisam Mokhtar1, Tarnya Marshall2, Suzanne Verstappen1, a score based on proximity of the H3K4me3 mark to the JIA SNP and Deborah Symmons1,3, Anne Barton1,3 and Darren Plant1,3 using permutation testing to evaluate statistical significance. 1Arthritis Research UK Centre for Epidemiology, University of Results: Significant enrichment of H3K4me3 marks overlapping JIA Manchester, Manchester, 2Department of Rheumatology, Norfolk associated SNPs was observed in regulatory T cells (P ¼ 0.003) CD19 and Norwich University Hospitals NHS Foundation Trust, Norwich primary cells (P ¼ 0.003), CD4 memory primary cells (P ¼ 0.003) CD4 and 3NIHR Musculoskeletal Biomedical Research Unit, Central naı¨ve primary cells (P ¼ 0.008) and CD34 primary cells (0.011). The Manchester University Hospitals NHS Foundation Trust, Manchester, enrichment seen in regulatory and CD4 T cells was driven by UK associations in RUNX1, ANKRD55, IL2-IL21, ATP8B2-IL6R, CCR1- CCR3, ERAP2-LNPEP, SH2B3-ATXN2 and PRM1-C16orf75. Background: RA is a chronic, systemic, autoimmune disease that is Conclusion: Genetic association signals in JIA overlap epigenetic characterized by synovial joint inflammation. Patients with RA are at markers of gene expression preferentially in T cells, particularly increased risk of premature death, with cardiovascular disease (CVD) regulatory, CD19, CD4 and CD34 T cells, guiding cell-type selection forming the primary cause. CXC ligand 12 (CXCL12), a potent pro- for future functional characterization of JIA associated loci. inflammatory chemokine, is elevated in RA SF promoting joint Disclosure statement: The authors have declared no conflicts of destruction, and previous studies have shown that CXCL12 plasma interest. levels are correlated with a variant at the CXCL12 locus (rs1746048). Previous studies have also correlated rs1746048 with coronary heart 253. A NOVEL TECHNIQUE TO DETERMINE CHROMATIN disease (CHD). We aimed to investigate the relationship between the INTERACTIONS GIVES INSIGHT INTO GENETIC MECHANISM marker rs1746048, along with 19 other CHD-associated SNPs, and all- OF RHEUMATOID ARTHRITIS cause and CVD mortality in RA. Methods: Patients were recruited from the Norfolk Arthritis Register Stephen Eyre1, Paul Martin1, Amanda McGovern1, Kate McAllister1, (NOAR), a primary care based prospective inception cohort of patients Annie Yarwood1, Jane Worthington1, Stefan Schoenfelder2, with new onset inflammatory polyarthritis (IP), defined as swelling of Takashi Nagano2, Simon Andrews3, Stephen Wingett3 and two or more joints, persisting for at least 4 weeks. DNA samples from Peter Fraser2 NOAR were genotyped for 20 genetic markers, including rs1746048, 1Institute of Inflammation and Repair, University of Manchester, using the Sequenom MassARRAY iPLEX system. Death certificates Manchester, 2Nuclear Dynamics and 3Bioinformatics, Babraham were obtained from the Office for National Statistics (ONS) and all- Institute, Cambridge, UK cause mortality or CVD mortality (International Classification of Diseases 10 code I) were used as the outcome. All patients were Background: There are now over 100 genetic loci robustly associated recruited from 1990 onwards and followed until death, embarkation or with RA susceptibility. In RA, like all autoimmune diseases, the majority 30 June 2013, whichever came first. Cox proportional hazard models of these associated genetic loci are situated outside traditional coding were used to investigate the association between marker allele dosage genes, and some reside a large distance from the nearest annotated and risk of all-cause mortality and CVD mortality, adjusting for known POSTER VIEWING III Thursday 30 April 2015 i149

CVD risk factors, (i.e. age, gender, smoking status and obesity showing the most upregulated differential expression between the (cholesterol, hypertension and diabetes; based on medication). response phenotypes (P-value 0.03). Results: A total of 2148 patients with IP were included in the study, of Conclusion: This study indicates that baseline whole blood expres- which 947 patients (44%) satisfied the ACR 1987 criteria for RA during sion profiling of RA patients using microarrays could be a useful tool in follow up. Median symptom duration prior to presentation was 7.9 the search for biomarkers predictive of response to etanercept, via the months [interquartile range (IQR) 3.1–15.3], and 1410 patients were identification of plausible candidate genes. However, perhaps due to female (66%). By 30 June 2013, 564 patients (26%) had died, and CVD small sample numbers or that the biological differences are modest was recorded on the death certificate for 290 patients (51% of all relative to the microarrays background noise, no genes remained deaths). rs1746048 was associated with increased risk of CVD significant following multiple testing. Results from the GSEA however mortality in RA in both unadjusted [hazard ratio (HR) 1.43, P ¼ 0.03)] are particularly interesting and suggest that microRNAs may be and adjusted analyses (HR 1.67, P ¼ 0.02). Moreover, carriage of two involved in determining treatment response. Further work is therefore copies of the rs1746048 minor allele was associated with CVD planned in pre-treatment serum samples of RA patients about to mortality at study-wide significance in both the unadjusted analysis undergo treatment with etanercept to replicate these findings. (HR 3.56, P ¼ 0.001) and following adjustment for known CVD risk Disclosure statement: S.L.S. is funded by an investigator-initiated factors (HR 5.58, P ¼ 0.002). No other SNP showed consistent studentship awarded to A.B. from Pfizer. All other authors have evidence of association. declared no conflicts of interest. Conclusion: We demonstrate the association of the CXCL12 rs1746048 variant with increased CVD mortality in patients with RA 256. ALTERED DNA METHYLATION ASSOCIATED WITH and identify a potential marker and therapeutic target for the early RHEUMATOID ARTHRITIS IN DISEASE DISCORDANT detection and management of RA patients. However, future validation MONOZYGOTIC TWINS studies will first be needed to determine the causal effect at the CXCL12 locus and assess the correlation between plasma CXCL12 Amy Webster1, Flore Zufferey2, Darren Plant3, Jordana Bell2, levels and CVD outcome in RA. Anne Barton1,3, Frances Williams2 and Jane Worthington1,3 Disclosure statement: The authors have declared no conflicts of 1Arthritis Research UK Centre for Genetics and Genomics, University interest. of Manchester, Manchester, 2Department of Twin Research and Genetic Epidemiology, King’s College London, London and 3NIHR 255. GENOME-WIDE TRANSCRIPTIONAL PROFILING OF Manchester Musculoskeletal Biomedical Research Unit, Manchester RHEUMATOID ARTHRITS PATIENTS: TOWARDS STRATIFIED Academy of Health Sciences, Manchester, UK MEDICINE Background: Epigenetic studies in RA using prevalent cases and 1 2 1 Samantha L. Smith , Darren Plant , Stephen Eyre , Kimme L. unrelated controls have indicated that DNA methylation is altered in 3 4 5 6 Hyrich , Ann W. Morgan , Gerry A. Wilson , John Isaacs and patients with RA. However case–control studies of unrelated indivi- 1,2 Anne Barton duals do not allow matching for important confounders such as the 1 Centre for Genetics and Genomics, Arthritis Research UK, Centre underlying genetic variability and environmental exposures, which may for Musculoskeletal Research, Manchester Academic Health influence disease development and the epigenome. By investigating Sciences Centre, University of Manchester, 2NIHR Manchester DNA methylation differences in disease discordant monozygotic (MZ) Musculoskeletal BRU, Central Manchester Foundation Trust and twins, such confounding effects may be mitigated, increasing the University of Manchester, 3Centre for Epidemiology, Arthritis power to detect alterations to the methylome associated with RA. Research UK, Centre for Musculoskeletal Research, Manchester Methods: Twin subjects were recruited from the RA Twin Study Academic Health Sciences Centre, University of Manchester, (Manchester) and TwinsUK (London). Each MZ twin pair (n ¼ 63) Manchester, 4Leeds Institute of Rheumatic and Musculoskeletal included one twin classified as having RA while the other was Medicine, University of Leeds and NIHR Leeds Musculoskeletal classified as not having RA at the time samples were collected. Biomedical Research Unit, Leeds, 5Academic Unit of Rheumatology, Whole blood DNA was bisulphite converted and an epigenome-wide Department of Infection and Immunity, The Medical School, association study was performed using the HumanMethylation450 University of Sheffield, Sheffield and 6NIHR Newcastle Biomedical BeadChip (Illumina). Probes with a detection-P-value >0.01 were Research Centre, Newcastle upon Tyne NHS Foundation Trust and removed. Following quantile normalization, differentially methylated Newcastle University, Newcastle upon Tyne, UK positions (DMPs) were identified using linear regression with adjust- ment for cell composition. 6 Background: RA can be a severely debilitating disorder if left Results: The top 10 DMPs had P-values of 6 10 or less. untreated. Fortunately, the treatment of RA was revolutionized in the Interestingly, the seventh most differentially methylated site early 2000s with the introduction of biologics. However, it is currently (cg03733278) in the ZNF74 gene was previously identified as being unknown a priori which biologic will be most effective in an individual differentially methylated in RA cases vs unrelated healthy controls. A patient. Currently, these agents are prescribed on a trial and error separate study also found this gene to be upregulated in early RA. basis; resulting in up to 40% of patients failing to respond Another DMP (cg07693617) in the PRKCZ gene was previously found satisfactorily. A predictive biomarker has yet to be identified to to be hypermethylated in RA fibroblast-like synoviocytes. accurately stratify treatment regimes. We hypothesize that whole Conclusion: This is the largest study to date of DNA methylation in RA blood expression profiling of RA patients, about to commence discordant MZ twin pairs. We have added to the evidence for an treatment with the biologic etanercept, will provide such a biomarker. association between DNA methylation and RA, particularly in the Methods: This study included 72 RA patients about to commence ZNF74 and PRKCZ genes. While further validation and replication treatment with etanercept. Total RNA was extracted from pre-treatment studies are required, these preliminary data support the hypothesis whole blood samples, previously collected into Tempus/PaxGene blood that DNA methylation is altered in patients with RA and provides a tubes as part of the Biologics in Rheumatoid Arthritis Genetics and plausible biological mechanism to account for the observed mono- Genomics Study Syndicate cohort. Using EULAR response criteria at zygotic twin discordance in RA. 3-month follow up, there were 38 non-responders and 34 responders. Disclosure statement: The authors have declared no conflicts of Following labelling and amplification, complementary RNA was loaded interest. onto Illumina’s HumanHT-12 v4 expression profiling BeadChips; target- ing over 47 000 probes. Differential gene expression analysis was 257. INCORPORATING GENOTYPIC VARIABILITY MAPPING conducted in the limma Bioconductor package, followed by gene set ENHANCES DISCOVERY OF RISK LOCI FOR RHEUMATOID enrichment analysis (GSEA) using the GSEA software. ARTHRITIS Results: A number of differentially expressed (DE) genes were identified between the response phenotypes. Among the top five DE John Bowes1, Darren Plant1, Sebastien Viatte1, Annie Yarwood1, 1,2 1,2 1 genes, BTN3A2 was the most interesting and biologically plausible Stephen Eyre , Jane Worthington and Wenhua Wei 1 candidate; yielding a log2 fold-change of 0.464 in responders Arthritis Research UK Centre for Genetics and Genomics, Institute compared with non-responders (P-value 9.56 105). This gene acts of inflammation and repair, University of Manchester and 2NIHR by inhibiting the release of IFN-g from activated T cells and lies within Manchester Musculoskeletal Biomedical Research Unit, Central the juxta-telomeric region of the MHC class 1 locus. However, Manchester NHS Foundation Trust, Manchester Academic Health following multiple testing, no P-values remained significant. A Science Centre, Manchester, UK limitation of single gene analysis is that a number of genes acting in concert may bring about the phenotypic response. GSEA was Background: Genome-wide association studies (GWAS) have suc- conducted using a pre-ranked list of all DE genes passing a P-value cessfully highlighted over 100 genetic loci associated with RA. GWAS threshold of <0.05. Most interestingly, a binding motif for the primarily consider additive genetic effects and rely largely on large microRNAs miR-125a and miR-125b was enriched in those genes sample sizes to detect loci with moderate or weak effects via meta- i150 Thursday 30 April 2015 POSTER VIEWING III

analysis of multiple cohorts. The new challenge is to interrogate GWAS genome-wide significance. We identified a variant in the PARK2 loci in the context of non-additive effects (e.g. gene interactions), gene (P ¼ 2.8 108) associated with LDD. Differential methylation at largely ignored in GWAS analysis, and relate these findings to plausible one CpG island of the PARK2 promoter was observed in a small biological interactions. Innovative approaches are needed to address subset of subjects (b ¼ 8.74 104, P ¼ 0.006). the challenge and enhance discovery of novel risk loci for RA. One Conclusion: LDD accounts for a considerable proportion of low back emerging method is genome-wide genotypic variability mapping pain and the pathogenesis of LDD is poorly understood. This work (vGWAS) that can prioritize potentially interacting loci without knowing provides evidence of association of the PARK2 gene and suggests interacting factors in advance. vGWAS concerns the difference of that methylation of the PARK2 promoter may influence degeneration of variability across marker genotypes harbouring also non-additive and the intervertebral disc. This gene has not previously been considered a environmental effects and thus is complementary to GWAS. vGWAS candidate in LDD and further functional work is needed on this hitherto has been successfully applied to quantitative traits but is not directly unsuspected pathway. applicable to diseases due to little quantitative variation provided by Disclosure statement: The authors have declared no conflicts of the dichotomous phenotypes. interest. Methods: Here we present a novel pipeline incorporating vGWAS into the GWAS framework to study RA at three pre-existing GWAS cohorts 259. LOCI ASSOCIATED WITH N-GLYCOSYLATION OF each genotyped with Immunochip. The pipeline uses a mixed model HUMAN IMMUNOGLOBULIN G ARE NOT ASSOCIATED WITH approach to predict polygenic liability risks of RA for unrelated RHEUMATOID ARTHRITIS SUSCEPTIBILITY, TREATMENT samples and the resultant environmental residuals as a quantitative RESPONSE OR OUTCOME: A MENDELIAN RANDOMIZATION trait in a subsequent vGWAS to detect loci with genotypic variability STUDY using an adapted Levene’s test. In addition, the pipeline performs a conventional GWAS for each cohort and considering vGWAS and Annie Yarwood1, Sebastien Viatte1, Yukimori Okada2, GWAS signals jointly to prioritize disease risk loci. Identified vGWAS Robert Plenge3, Anne Barton1, Deborah P. Symmons4, loci are further tested for interactions between and with available Jane Worthington1 and Steve Eyre1 environmental factors. 1Arthritis Research UK Centre for Genetics and Genomics, Results: Based on the Immunochip-wide significance threshold University of Manchester, Manchester, UK, 2Brigham and Women’s (P < 2.3 105), vGWAS significant signals included known RA loci Hospital, Harvard Medical School, 3Merck Research Laboratories, HLA, PTPN22, ANKRD55 and TNFAIP3 that were also significant in the Merck & Co .Inc., Boston, MA, USA and 4Arthritis Research accompanying GWAS, as well as RA loci REL, STAT4 and TLE3 and UK Centre for Epidemiology, University of Manchester, novel loci TGFBR3, GRM7 and DOK6 that were not significant in the Manchester, UK accompanying GWAS. Applying a joint voting approach that requires at least moderate signals (e.g. P < 0.001) from vGWAS and GWAS Background: Glycosylation, of serum IgG has long been implicated in simultaneously to the sub-significant results we prioritized additional RA, with a lack of total IgG Fc galactosylation shown to correlate with loci enriched for RA loci confirmed mostly via meta-analyses including RA disease activity and severity. A recent genome-wide association PTPRC, SPRED2, BANK1, CCL21, RUNX1, CD80, ELMO1, FCGR2A, study identified nine confirmed loci (P < 2.27 109) and seven IRF8, STAT1 and TNIP1. Joint voting also suggested a number of novel strongly suggestive loci (P < 5 108) associated with N-glycosylation loci including COBOL, HORMAD2, IL5, RGS1 and UHRF1BP1. All the of human IgG. Several of these loci have also been associated with loci above had replicated vGWAS signals in at least one cohort. autoimmune disease (AID) susceptibility; therefore it has been Statistically significant interactions were detected between the suggested that there may be pleiotropy between loci controlling N- vGWAS loci within the HLA region and between HLA and anti- glycosylation and loci controlling AIDs. To investigate to what extent citrullinated peptide antibody across three cohorts on both dichot- the genetic evidence does support a role for N-glycosylation omous and liability scales. contributing to RA, we performed a Mendelian randomization study Conclusion: We conclude that the vGWAS empowered pipeline has testing variants associated with levels of IgG N-glycosylation for the potential to enhance discovery of RA risk loci at even the individual association with RA susceptibility, treatment response and severity. cohort level. The association of the same variants in the same genes that control Disclosure statement: A.Y. has received research funding from the IgG N-glycosylation with susceptibility to RA provides an unbiased test Innovative Medicines Initiative Joint Undertaking. W.W. has received of the hypothesis that N-glycosylation is important in RA (Mendelian research funding from the Higher Education Funding Council for randomization). England. All other authors have declared no conflicts of interest. Methods: Fifteen SNPs showing association with IgG N-glycosylation were analysed for association with RA susceptibility in 14 361 RA 258. EPIGENETIC REGULATION IMPLICATED IN LUMBAR cases and 43 923 controls of European ancestry. Five of the SNPs DISC DEGENERATION associated with glycosylation were tested for association with response to anti-TNF therapy in 1081 RA patient samples from the Frances M. Williams1, Aruna Bansal2, Joyce van Meurs3, Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS), Jordana Bell1, Ingrid Meulenbelt4,PradeepSuri5, Alex J. MacGregor1, measured by both change in DAS for 28 joints and EULAR response Andre Uitterlinden3 and Tim Spector1 criteria after 6 months. The same five SNPs were tested for association 1Twin Research, King’s College London, London, 2Acclarogen Ltd, with disease severity, measured by erosions or Larsen score in 345 St John’s Innovation Centre, Cambridge, UK, 3Department of Internal patients from the Norfolk Arthritis Register (NOAR). Medicine, Erasmus MC, Rotterdam, 4Department of Molecular Results: Testing 15 SNPs, previously associated with glycosylation, Epidemiology, Leiden University Medical Centre, Leiden, The revealed 14 SNPs with no evidence for association to RA suscept- Netherlands and 5VA Seattle Healthcare System, University of ibility. One SNP (rs9296009) did show a strong association with RA Washington, Seattle, WA, USA (P ¼ 6.92 10266), although it lies within the HLA region, modestly correlated with the lead SNP and unlikely to be the causal SNP in the Background: Lumbar disc degeneration (LDD) is an important cause region. Four regions of the genome did harbour SNPs associated for of episodes of severe and disabling low back pain, which is a common both traits, (shared loci), although statistical analysis indicated that the and costly problem to society. LDD is characterized by disc space associations observed for the two traits at these loci are independent. narrowing and osteophyte growth at the circumference of the disc. To Testing SNPs associated with glycosylation for association with date, the agnostic search of the genome by genome-wide association response to anti-TNF therapy showed no evidence of association. (GWA) to identify common variants associated with LDD has not been One SNP rs12342831 was modestly associated with Larsen score in fruitful. We performed a GWA meta-analysis of LDD in cohorts of patients meeting ACR criteria cumulatively after 5 years (n ¼ 342, Northern European extraction and searched for evidence of differential P ¼ 0.054). No association was seen with erosions. methylation in the most highly associated gene identified. Conclusion: In a large, well powered cohort of RA patients, a Methods: We have developed a continuous trait based on disc space Mendelian randomization approach showed no evidence to support narrowing and osteophytes growth which is measurable on all forms of the hypothesis that N-glycosylation of IgG is associated with imaging (plain radiograph, CT scan and MRI) and performed a meta- susceptibility to RA, anti-TNF treatment response or disease severity. analysis of five cohorts of Northern European extraction each having On the contrary, our analysis showed that SNPs driving levels of GWA data imputed to HapMap version 2. In a subset having glycosylation have no association to RA, indicating localization of information about whole blood methylation obtained using the associated SNPs should not be taken as shared genetic background. Illumina 27 k chip evidence of differential methylation was sought. Disclosure statement: R.P. is an employee of Merck. All other Results: This study of 4600 individuals identified four single nucleotide authors have declared no conflicts of interest. polymorphisms (SNPs) with P < 5 108, the threshold set for POSTER VIEWING III Thursday 30 April 2015 i151

261. A PROSPECTIVE STUDY EXAMINING THE SENSITIVITY OF ULTRASOUND DETERMINED MEDIAN NERVE CROSS- IMAGING SECTIONAL AREA WITH NERVE CONDUCTION INVESTIGATION IN THE DIAGNOSIS OF CARPAL TUNNEL SYNDROME

1 2 2,3 260. A BETA-BINOMINAL REGRESSION MODEL TO Beena Hameed , Tamim Khanbhai , Peter Resteghini and 3 PREDICT DOPPLER SCORE ON ULTRASOUND EXAMINATION Stephen Bourke 1 2 3 IN PATIENTS WITH INFLAMMATORY HAND JOINT PAIN Rheumatology, Sports Medicine and Radiology, Homerton University Hospital, London, UK Coziana Ciurtin1, Karol Wyszynski2, Jessica Manson1 and 2 Giampierro Marra Background: Diagnosis of carpal tunnel syndrome (CTS) with nerve 1 2 Department of Rheumatology and Department of Statistics, conduction studies (NCS) rests upon demonstrating impaired median University College London, London, UK nerve conduction across the carpal tunnel in the context of normal conduction elsewhere. Imaging techniques provide alternative means Background: US assessment of small joints is essential for the of diagnosis for CTS. The commonly applied techniques are; MRI and diagnosis of polyarticular inflammatory arthritis and guidance of the US. High-resolution US allows non-invasive imaging of the carpal therapeutic decisions in patients with established RA. The access to tunnel and its contents with several advantages over MRI, including US varies among hospitals and rheumatology services. Even if a being relatively fast and inexpensive and allowing additional dynamic considerable proportion of patients with hand joint pain or established and blood flow imaging with relatively little additional time. This study RA might have subclinical inflammation, it is not cost-effective to examines sensitivity of US in confirming CTS in comparison with NCS screen them all. The aim of our study was to build a statistical model to in patients with clinically defined CTS. assess the influence of several outcome measures (such as number of Methods: 28 patients (56 wrists; mean age 53 years, range 25–85 tender joints (TJC) and swollen joints (SJC) out of 28, global visual years) with CTS were enrolled. Clinical parameters were recorded at analogue scale (GVAS), CRP, ESR, presence of RF and anti-CCP one time point by Phalen’s test, sensory deficit and motor deficit in antibodies, disease duration and medication) on the presence of a median nerve distribution by two clinicians by consensus who were power Doppler signal at the US examination of hand joints. blinded to either NCS or US findings. US assessment (Grey scale and Methods: We proposed a regression model to assess the contribution power Doppler using GE Logic E9 and a ML6-15 Hz transducer) of the of every outcome measure to the risk of having active joint median nerve was performed [cross-sectional area (CSA) measure- inflammation as well as predict the power Doppler signal. We excluded ment at the proximal carpal tunnel, at the level of the pronator patients with a power Doppler signal present in more than 10/22 joints quadratus muscle and 12 cm proximally in the mid forearm] by two to ensure homogeneity in the data. We conducted a real-life study observers (radiologist or trained radiographer) by consensus; they including 276 patients referred for the suspicion of active joint were blinded to clinical or NCS examination of these patients. In inflammation (new referrals for the suspicion of inflammatory arthritis, addition the flexor retinaculum was assessed for degree of bowing and RA patients and patients with other inflammatory rheumatic condi- the median nerve was assessed for intra-neural hyper-vascularization. tions). We assessed 22 hand joints in every patient, irrespective of their The relation between each measure of median nerve assessment was hand symptoms, using the OMERACT scoring system for power determined by Spearman correlation analysis. Doppler signal. All patients had clinical assessments and laboratory Results: US diagnosed more wrists with median nerve pathology tests within 2 weeks from the US scan. The proposed regression 50/56 (88%) than EMG 38/56 (53%). Overall, no strong correlations model was based on a beta-binomial distribution (1, disease present; were found between clinical measures and either EMG or US (CSA). 0, disease absent) for the power Doppler score variable and a mix of US (CSA) co-related significantly with EMG (P ¼ 0.007). The wrist-to- main interaction effects for the outcome measures stated above. forearm (WFR) measures correlated weakly with the EMG (P ¼ 0.205). Negative interaction effects showed that the respective outcome was Conclusion: In CTS US examination performed over and above NCS associated with a lower number of joints with power Doppler signal. in confirming diagnosis. Milder cases where NCS reports normal Results: Table 1 summarizes the marginal effects of different variables examination may be diagnosed by US examination. Larger studies are on the number of joints with Doppler signal at the US examination in needed to determine the relative predictive power of US in diagnosing newly referred patients for the suspicion of inflammatory arthritis or mild CTS. previous diagnosis of RA, and patients with other inflammatory Disclosure statement: The authors have declared no conflicts of conditions. interest. Conclusion: Our statistical model suggested that patients with RA diagnosis treated with tocilizumab tend to have a lower power Doppler score than patients treated with other biologics or DMARDs, despite 262. PSORIATIC ARTHRITIS ULTRASOUND VS CLINICAL similar clinical and laboratory findings. The presence of RF increased EXAMINATION (PAUSE) STUDY the power Doppler score only in patients with clinical suspicion of inflammatory arthritis. CRP and ESR had almost no effect on Andrew I. Rutherford1, Cassandra Hong1, Bruce Kirkham1 and predicting power Doppler. Out of all three clinical outcomes, TJC, Toby Garrood1 SJC and GVAS, only the SJC correlated with an increased power 1Rheumatology, Guy’s and St Thomas’ NHS Foundation Trust, Doppler score and only in patients with RA. We plan to use this London, UK prediction model to improve the referral criteria to our US clinic and minimize the risk of underdiagnosing active inflammatory arthritis. Background: Anti-TNF therapy is standard second-line treatment for Disclosure statement: The authors have declared no conflicts of patients with moderate-to-severe PsA. Current UK (National Institute interest. for Health and Care Excellence) guidelines state that, as well as failing

260 TABLE 1. Marginal effects of a selection of outcomes on the power Doppler score (magnitude of effect and CI) RA status 0 0 1 Clinical suspicion of inflammatory 010 arthritis with no previously established diagnosis of a rheumatic condition RF 2.76 (2.32, 3.21) 0.11 (0.25, 0.46) 0.09 (0.23, 0.06) CCP 0.75 (1.07, 0.42) 0.01061559 (0.35, 0.37) 0.65 (0.50, 0.80) MTX NA NA 0.01 (0.12, 0.13) Adalimumab NA NA 0.79 (0.58, 1.01) Etanercept NA NA 0.01 (0.12, 0.13) Rituximab NA NA 0.62 (0.45, 0.79) Tocilizumab NA NA 1.81 (1.90, 1.72) CRP 0.0278 (0.0277, 0.0279) 0.004856 (0.004850, 0.004862) 0.0546 (0.0544, 0.0547) ESR 0.01551 (0.01548, 0.01555) 0.01880 (0.01871, 0.01889) 0.007728 (0.007725, 0.007731) TJC 0.00915 (0.00917, 0.00914) 0.02020 (0.02010, 0.02030) 0.0018359 (0.0018360, 0.0018357) SJC 0.100 (0.099, 0.102) 0.086 (0.0841, 0.0879) 0.214 (0.212, 0.216) GVAS 0.004594 (0.004590, 0.004597) 0.01021 (0.01024, 0.01019) 0.005323 (0.005324, 0.005321) GVAS: global visual analogue scale; SJC: swollen joint count; TJC: tender joint count. i152 Thursday 30 April 2015 POSTER VIEWING III

conventional DMARD treatment, patients must also have a minimum of addition, cluster analysis of patient observations was also performed in three swollen and three tender joints. The assessment of swollen joints order to identify homogeneous subgroups of patients in terms of can be quite subjective with large inter-observer variation. Existing comorbidities as represented by these variables. Subsequently, gout studies have demonstrated that US is more sensitive than clinical characteristics, lifestyle factors, comorbidities and medication use were examination for the detection of synovitis in early PsA patients not yet compared across the clusters. on DMARD treatment. The aim of this study was to investigate the Results: 1184 completed questionnaires were received (response presence of subclinical synovitis in established PsA patients with less 66%). Of these, 1024 consented to medical record review and had than three swollen joints but meeting all of the other eligibility criteria complete comorbidity data. Factor analysis revealed four distinct for anti-TNF therapy. clusters: F1 correlated with heart disease, diabetes and hyperlipidae- Methods: 15 participants with PsA, meeting classification of Psoriatic mia; F2 correlated with renal failure and hypertension; F3 correlated Arthritis Criteria (PsARC), were recruited from the rheumatology with obesity; and F4 correlated with liver disorders. With regards to department at Guy’s Hospital. All patients had clinically active disease clustering on patient observations, five comorbidity clusters (C1–C5) (three or more tender joints) despite at least two DMARDs. Each were identified. Cluster C1 (n ¼ 167, 16%) combined people with patient had a PsARC assessment completed. An US examination was obesity (n ¼ 167, 100%), hypertension (156, 93%) and metabolic carried out of 40 joints (shoulders, elbows, wrists, MCPs, proximal syndrome (125, 75%), had the most frequent gout attacks and history interphalangeals, knees, ankles and MTPs bilaterally). Greyscale of oligo/polyarticular attacks and was most likely to be prescribed scores of 2 or power Doppler scores of 1 were used as definitions allopurinol. C2 (n ¼ 279, 27%) was dominated by hypertension (233, of US synovitis. A selection of the images was reviewed by a second 84%). C3 (n ¼ 254, 25%) consisted of people with few comorbidities sonographer and inter-observer agreement was calculated using and was associated with daily alcohol consumption. C4 (n ¼ 212, 21%) Cohen’s k. HAQ and DAS for 28 joints (DAS28) assessments were had the greatest proportions of people with renal failure (134, 63%) also completed along with routine blood tests (ESR and CRP). A and diabetes (89, 42%). All participants in C5 (n ¼ 112, 11%) were Wilcoxon signed rank test was used to test for significant differences obese but had no other comorbidities. between inflamed joints as determined by US and clinical examination. Conclusion: In this primary care gout population, five different comorbid- Correlation between US joint counts and other measures was also ity clusters were identified. While hypertension and obesity occurred examined. across multiple clusters, distinct clusters were identified characterized by Results: 80% of the participants had evidence of subclinical synovitis renal failure and diabetes, and low levels of comorbidity. These clusters (defined as the presence of US synovitis in the absence of clinically may provide insights into the pathogenesis of comorbidity in gout and apparent swelling) in at least one joint. The mean US joint count was 3 guide which patients should be screened for comorbid conditions. compared with the mean swollen joint count of 0.73 (P ¼ 0.009). 5/15 Disclosure statement: The authors have declared no conflicts of participants would be eligible for anti-TNF treatment if US were used in interest. parallel with clinical examination to detect synovitis. There was a positive correlation seen between US joint count and DAS28 score 264. DISTRIBUTION OF HAEMOCHROMATOSIS (r ¼ 0.58, P ¼ 0.022) but not with other measures. The inter-observer ARTHROPATHY. HIGH ANKLE AND MIDFOOT PREVALENCE; correlation in grading the US scans was good with k ¼ 0.68. A DIAGNOSTIC CLUE? Conclusion: In this pilot study, US was superior to clinical examination at detecting synovitis in PsA. If US were used in addition to clinical Alex Richardson1 and Patrick D. W. Kiely1 examination to assess joint inflammation a third of the patients studied 1Rheumatology, St George’s Healthcare NHS Trust, London, UK would have been eligible for anti-TNF. Larger studies are needed to replicate this finding. These results suggest that US could be used to Background: Long delays in diagnosis of haemochromatosis are stratify patients with PsA for ant-TNF treatment, a hypothesis which frequent and lead to an adverse effect on hepatic and cardiac could be tested in prospective studies. outcome. Arthropathy is a highly prevalent and early feature, which Disclosure statement: B.K. has received consulting fees from could act as a trigger for diagnosis if sufficiently distinctive. We AbbVie, BMS, Celgene, Novartis and UCB. All other authors have conducted a survey of patients with haemochromatosis to assess the declared no conflicts of interest. prevalence and distribution of joint symptoms and their relation to the diagnosis. Methods: A questionnaire was sent to members of the UK Haemochromatosis Society (1300) in December 2013. Questions assessed how the diagnosis of haemochromatosis was made; METABOLIC AND CRYSTAL symptoms, duration, the prevalence and distribution of affected ARTHROPATHIES joints and the role of a rheumatologist. Results: Questionnaires were returned by 470 people with haemo- chromatosis, 97% white, 53% male. The genotype was C282Y homozygous 52%, C282Y/H63D heterozygous 7%, C282Y/wild-type heterozygous 5%, unknown 33%. The diagnosis was made at a mean 263. COMORBIDITY CLUSTERS IN PEOPLE WITH GOUT: A age of 56 years, following family member screening in 20%, well man/ PRIMARY CARE BASED OBSERVATIONAL STUDY woman screening in 23% and as result of symptoms in 57%. At Megan Bevis1, Milisa Blagojevic-Bucknall1, Christian D. Mallen1, diagnosis the most frequent symptoms attributed to haemochroma- Samantha L. Hider1 and Edward Roddy1 tosis were fatigue 65% and joint pain 60%, with a mean duration of 8 1Research Institute for Primary Care and Health Sciences, Keele years (0–65) and mean ferritin 1752 mg/l. The diagnosis was most University, Keele, UK frequently made by a general practitioner (38%), followed by a haematologist (24%), a gastroenterologist (21.5%) and a rheumatol- Background: Gout is the most prevalent inflammatory arthritis and is ogist (7%). 88% of respondents reported joint pain, stiffness or associated with considerable comorbidity, including obesity, hyperten- swelling. Joint symptoms preceded the diagnosis of haemochroma- sion, diabetes and cardiovascular disease. Inter-relationships between tosis by more than 5 years in 47%, by more than 1 year in 78.5% and different comorbidities in gout are poorly understood. A recent French post-dated the diagnosis in 14.5%. The most prevalent areas affected study described five distinct comorbidity clusters, but included were hand or wrist (66%), ankle or mid-foot (49%) and knee (44%). In participants from secondary care, reducing the generalizability of the the hands, the prevalence of symptoms was first CMC 60%, wrist results to most patients with gout, who are treated exclusively in primary 52%, MCP 47%, proximal interphalangeal (48%) and distal inter- care. The objective of this cross-sectional analysis was to investigate phalangeal joints (41%). No formal arthritic diagnosis was given to comorbidity clustering in patients with gout in UK primary care. 45% and a diagnosis of OA was given to 29% and haemochromatosis Methods: All adults aged 18 years registered with 20 general practices arthropathy to 11.5%. Dupuytren’s disease was reported by 13% of in the West Midlands who had consulted their general practitioner about men and 8% of women. Venesection was reported to have helped joint gout or been prescribed allopurinol or colchicine in the preceding 2 years symptoms in 5%, made no impact in 20% and in 51% new joints had were mailed a questionnaire and asked for consent to review their become affected following de-ironing. A negative impact on employ- medical records. Gout characteristics (duration, attack frequency, ment from arthropathy was reported by 21%, with 9% losing their job. history of oligo/polyarticular attacks), BMI and alcohol consumption Conclusion: In haemochromatosis, joint symptoms are highly pre- were assessed in the questionnaire. Comorbidities (via Read codes), valent at diagnosis, with the ankle and mid-foot involved in 49%. In prescriptions and presence of tophi were ascertained from primary care addition to MCP joint disease, an OA-like presentation at a relatively medical records of consenting participants over the preceding 2 years. young age in the hind or midfoot might be a distinguishing feature to Factor analysis was performed to obtain distinct clusters of variables prompt investigations leading to an earlier diagnosis. including hypertension, obesity, diabetes, hyperlipidaemia, heart failure, Disclosure statement: The authors have declared no conflicts of coronary heart disease, renal failure, liver disorders and cancer. In interest. POSTER VIEWING III Thursday 30 April 2015 i153

265. THE MANAGEMENT OF GOUT WITHIN PRIMARY AND severe subtype of JIA, is expected to be linked to an increase in SECONDARY CARE: A COMPARISON mortality compared with other subtypes although evidence is so far 1 2 lacking. The main objective was to calculate the standardized mortality Lauren Steel and Tom J. Walton rates (SMR) in children with severe JIA, defined as requiring biologic 1Rheumatology, Southend Hospital University NHS Foundation 2 therapy. Trust, Westcliff-on-Sea and Rheumatology, Colchester Hospital Methods: The study population comprised JIA subjects recruited to University NHS Foundation Trust, Colchester Hospital, UK the BSPAR Etanercept Cohort Study. Deaths were identified through regular follow up via hospital questionnaires and links to ONS. This Background: Gout is a potentially curable inflammatory arthritis analysis followed all patients from registration until death, last follow- caused by deposition of MSU crystals within the joint, typically up date, or 31 December 2012, whichever came first. Poisson causing a painful monoarthritis. British Society for Rheumatology regression calculated crude incidence rates per 1000 person-years guidelines provide a management framework and they apply to (p-years). SMRs were calculated using age- and gender-specific primary and secondary care settings. This is an audit of the manage- mortality rates in the UK population. ment of gout in Colchester, North Essex, within the hospital Results: Patients had a mean age of 11 years at entry to the study, rheumatology department and primary care. with a median disease duration of 4 years and treatment histories of Methods: This was a retrospective audit searching for gout over the numerous long-term medications. Patients with systemic JIA had past 3 years. In the rheumatology department, a search of BigHand longer mean follow up in the study (8 years vs 6 years). Seven deaths letters and exclusion of patients without gout as a diagnosis within the were reported in total, with an expected rate of 0.96. Four of the letter identified 84 patients. Within primary care, 88 patients were deaths occurred in systemic JIA patients. The incidence rate is 1.6 per identified on SystmOne with a coded gout episode. The following 1000 p-years with an SMR of 7.3 (95% CI 2.9, 15.0). Patients with criteria were subsequently applied: frequency and/or duration of acute systemic JIA and non-systemic JIA also had high SMRs (Table 1). flare; initial treatment proposed; check serum urate level; lifestyle Causes of death included macrophage activation syndrome, sepsis modification advised; medication review undertaken; assessment of and two in association with stem-cell transplants. cardiovascular risk (i.e. blood pressure/lipids/glucose); and implemen- Conclusion: In a select group of patients with severe JIA, there tation of urate-lowering therapy if indicated (i.e. >1 attack per year) appears to be a high mortality rate, particularly among those with Results: The results (Table 1) demonstrate that gout management can systemic disease, compared with a healthy paediatric population. be improved within both primary and secondary care. Similar criteria for While death is still a rare outcome, this study highlights the importance both general practitioners (GPs) and rheumatologists to address are of the diagnosis of JIA. documentation of flare frequency/duration, lifestyle advice and review of Disclosure statement: The authors have declared no conflicts of medications. GPs are less likely to measure serum urate than interest. rheumatologists as well as to start urate-lowering therapy.

Rheumatologists also more frequently assess cardiovascular risk. 266 TABLE 1. BSPAR: mortality rates in the BSPAR Etanercept Cohort Study Despite the gold standard investigation for the diagnosis of gout being confirmation of negatively birefringent urate crystals under polarized light Total JIA Systemic JIA Non-systemic microscopy, aspiration was undertaken in 25% of cases in hospital and cohort JIA 2% of cases in primary care. Moreover, the provision of written Subjects, n 693 99 594 information about the diagnosis was performed in 15.9% and 17% for Exposure, p-years 4475 795 3680 —Male 1500 329 1171 patients attending their GP and rheumatologist, respectively. —Female 2975 466 2509 Conclusion: Despite national guidelines for best practice gout Total deaths, n (%) 7 (1) 4 (4) 3 (0.5) management, both GPs and rheumatologists can improve their —Male, n (%) 1 (0.1) 0 1 (0.2) management according to this audit. Better documentation is required —Female, n (%) 6 (0.9) 4 (4) 2 (0.3) for flare frequency/duration, medication review and lifestyle advice by Expected deaths, n 0.96 0.18 0.78 all doctors treating gout. GPs should measure serum urate and —Male 0.46 0.10 0.35 implement urate-lowering therapy more frequently. Rheumatologists —Female 0.50 0.08 0.42 Mortality incidence 1.6 (0.6, 3.2) 5.0 (1.4, 12.9) 0.8 (0.2, 2.4) need to lead by example to educate colleagues on appropriately rate/1000 p-years managing this condition with patient involvement. (95% CI) Disclosure statement: The authors have declared no conflicts of —Male 0.7 (0.02, 3.7) — 0.9 (0.02, 4.8) interest. —Female 2.0 (0.7, 4.4) 8.6 (2.3, 22.0) 0.8 (0.1, 2.9) SMR (95% CI) 7.3 (2.9, 15.0) 21.7 (5.9, 55.4) 3.9 (0.8, 11.3) —Male 2.2 (0.06, 12.2) — 2.8 (0.07, 15.8) 265 TABLE 1. Compliance comparison between primary and secondary care —Female 11.9 (4.4, 25.9) 49.5 (13.5, 126.8) 4.7 (0.6, 17.0) Criterion Primary care Secondary care BSPAR: British Society for Paediatric and Adolescent Rheumatology; p-years: compliance, % compliance, % person-years. Flare duration/frequency 61.0 67.0 Initial treatment proposed 90.9 89.2 Serum urate measured 34.1 98.0 Lifestyle advice 52.3 56.4 267. TREATMENT PRESCRIBING PATTERNS IN A COHORT Medication review 34.1 60.0 OF PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS: DATA Cardiovascular risk assessment 63.6 90.5 FROM THE CHILDHOOD ARTHRITIS PROSPECTIVE STUDY Urate-lowering therapy (if indicated) 68.0 95.2 Rebecca Davies1, Roberto Carrasco1, Helen E. Foster2, Eileen M. Baildam3, Alice S. E. Chieng4, Joyce E. Davidson5, Yiannis Ioannou6, Lucy R. Wedderburn7, Wendy Thomson1, Kimme L. Hyrich1 on behalf of the Childhood Arthritis Prospective Study1 1Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, 2Musculoskeletal Research Group, Newcastle PAEDIATRIC AND ADOLESCENT University and Paediatric Rheumatology, Newcastle upon Tyne, RHEUMATOLOGY 3Department of Paediatric Rheumatology, Alder Hey Children’s Hospital NHS Foundation Trust, Liverpool, 4Department of Rheumatology, Royal Manchester Children’s Hospital, Manchester, 5Department of Paediatric Rheumatology, Royal Hospital for Sick 6 266. STANDARDIZED MORTALITY RATES ARE INCREASED Children, University of Glasgow, Glasgow, Arthritis Research UK Centre for Adolescent Rheumatology, University College London and IN PATIENTS WITH SEVERE JUVENILE IDIOPATHIC 7 ARTHRITIS Rheumatology Unit, Institute for Child Health, University College London and Great Ormond Street Hospital NHS Trust, London, UK Rebecca Davies1, Taunton Southwood2, Lianne Kearsley-Fleet1, Mark Lunt1, Kimme L. Hyrich1 on behalf of the British Society for Background: JIA is a heterogeneous disease, classified according to Paediatric and Adolescent Rheumatology ETN Cohort Study1 the ILAR. Initial treatment of the various presentations is based largely 1Arthritis Research UK Epidemiology Unit, University of Manchester, on disease severity; intra-articular injections for oligoarthritis, MTX for Manchester and 2Institute of Child Health, University of Birmingham, polyarthritis and systemic presentations. The recent licensing of Birmingham, UK biologic therapies for use in JIA has revolutionized treatment of the disease. It is not currently known what proportion of children who Background: Mortality rates in children with JIA are increased present with polyarthritis will require biologic therapy. Although not compared with the general population. Systemic arthritis, a more studied formally, it is also recognized a proportion of children with i154 Thursday 30 April 2015 POSTER VIEWING III

oligoarthritis will also require systemic therapy to control symptoms. problems. For example, negatively worded items led ‘incongruent The aim of the study was to describe prescribing patterns within a endorsement’ meaning that responses to these items reflected the cohort of patients with new onset JIA over the first 3 years following opposite response to the one intended. These results in addition to the presentation to rheumatology. thematic analysis determined the modifications of the IPQ-R and the Methods: Children with at least 3 years of follow up within the development of new items of the PPQ-YP. The participants who Childhood Arthritis Prospective Study, a prospective observational reviewed the PPQ-YP completed a detailed feedback questionnaire inception study of inflammatory arthritis, were included. For analysis, and this led to further modifications. 65 adolescents with juvenile children were placed into one of four groups based on physician- arthritis completed version 2, Cronbach’s alpha for the domains assigned ILAR category and number of active joints at first presenta- ranged from 0.60 for personal control to 0.93 for emotional tion (baseline): oligoarthritis (oJIA), polyarthritis (pJIA), systemic (sJIA) representation. Further validation and re-test reliability testing of this and enthesitis-related arthritis (ERA). Treatment exposures over 3 version of the PPQ-YP is currently underway. years were determined and categorized into NSAID, intra-articular Conclusion: Currently, there are no validated adolescent question- steroids and DMARDs including MTX and biologics including naires that capture the full range of pain beliefs related to JIA. The adalimumab (ADA), etanercept (ETN), infliximab (INF) and tocilizumab PPQ-YP is a theory-driven questionnaire consisting of nine domains of (TCZ). pain beliefs. By using a framework that clearly defines the relationship Results: 712 children were included (406 with oJIA, 221 with pJIA, 42 between beliefs outcomes it is hoped that data generated by the PPQ- with sJIA and 43 ERA; Table 1). Over a 3-year period, almost 100% of YP will provide stronger predictors of an adolescent’s behaviour by children with pJIA and 50% of children with oJIA went on to receive a facilitating better assessment of adolescent beliefs. This can lead to DMARD. 46% with pJIA and 17% with oJIA also received a biologic. the development of new interventions for adolescents with JIA. The most recent ILAR category among children with oJIA who Disclosure statement: The authors have declared no conflicts of subsequently received a biologic included 39% of those with extended interest. oJIA, 19% of those with pJIA, 4% of those with ERA and 11% of those with other subtypes; 27% had persistent oJIA. All sJIA patients were 269. FAT PATTERNING AND METABOLIC ABNORMALITIES treated with DMARDs with 36% receiving biologics (7% ADA, 33% IN CHILDREN WITH JUVENILE DERMATOMYOSITIS: ETN, 33% INF, 13% TCZ, 13% unknown). 63% of ERA patients DESCRIPTIVE STUDY received a DMARD with 26% going on to receive a biologic drug. Conclusion: Over a 3-year period, almost all patients with pJIA Anju Gupta1, R. Chethan1, Anil Bhalla1, Amit Rawat1 and received treatment with MTX and almost 50% required biologics. A Surjit Singh1 high proportion of children presenting with oJIA also received 1Paediatrics, Postgraduate Institute of Medical Education and DMARDs and biologics, with many children receiving such treatments Research, Chandigarh, India for persistent oJIA, despite the lack of clinical trial evidence for effectiveness in this subtype. Further studies on the effectiveness in Background: JDM is the most common idiopathic inflammatory this subtype should be undertaken to ensure appropriate use of myopathy in children affecting predominantly muscles and skin, and is advanced therapies in this population. also associated with long-term complications like lipodystrophy (LD), Disclosure statement: K.L.H. has received honoraria from AbbVie calcinosis and interstitial lung disease. LD is frequently associated with and Pfizer. All other authors have declared no conflicts of interest. insulin resistance and hyperlipidaemia. Diagnosis is usually made by physical appearance few years after initial diagnosis. We aimed to 267 TABLE 1. Treatment prescribing patterns within the CAPS cohort quantify and study the patterns of fat distribution and metabolic derangements in a cohort of patients with JDM. Arthritis pattern at presentation n Ever had a Ever had a DMARD, n (%) biologic, n (%) Methods: The study was approved by Institute Ethics Committee. Informed consent was obtained from cases as well as controls (or their Oligoarthritis 406 204 (50) 70 (17) Polyarthritis 221 217 (98) 98 (44) parents, as applicable) prior to inclusion in the study. Twenty-six Systemic JIA 42 42 (100) 15 (36) patients with JDM along with age and sex-matched controls were Enthesitis-related arthritis 43 27 (63) 11 (26) enrolled and divided into two groups: one less than 5 years of follow up after diagnosis and another more than 5 years of follow up after CAPS: Childhood Arthritis Prospective Study. diagnosis. Basic anthropometric parameters and subcutaneous skinfold thickness were measured in both patients and controls. Glucose tolerance test, serum lipid and leptin levels were measured 268. VALIDATING A PAIN PERCEPTION QUESTIONNAIRE only in the study group. FOR YOUNG PEOPLE WITH JUVENILE ARTHRITIS Results: The mean age of patients enrolled was 14.08 5.43 years Daniela Ghio1, Rachel Calam2, Kimme L. Hyrich3, Wendy Thomson1, with mean interval from initial diagnosis of 5.86 3.91 years. LD was Childhood Arthritis Prospective Study1,3 and Lis Cordingley1 present in 14 patients, equally distributed between two groups. 1NIHR Manchester Musculoskeletal Biomedical Research, 2School of Calcinosis, acanthosis and hirsutism were frequently seen in patients Psychological Sciences and 3Arthritis Research UK, Centre for with LD. JDM patients had lower mean weight and height compared Musculoskeletal Research, University of Manchester, Manchester, UK with controls. Medial calf thickness was significantly lower in patients (P ¼ 0.003). Lower BMI, triceps and subscapular skin fold thickness in Background: The ways in which people perceive their illness are addition to medial calf thickness was seen in the subgroup of patients known to affect long-term outcomes. The Common Sense-Self- with LD compared with respective controls. Hypertriglyceridaemia and Regulatory Model (CS-SRM) is used as a theoretical framework to high cholesterol and LDL levels were seen frequently in patients. Low investigate the influence of illness beliefs on outcomes and the leptin levels were seen in 10 patients; nine had LD. Revised Illness Perception Questionnaire (IPQ-R) is used to assess key Conclusion: LD was present in half of our patients. Medial calf illness beliefs. However, these approaches have rarely been used with thickness was significantly lower in patients with LD and in patients adolescents nor is there a validated adolescent version of the IPQ-R. with longer follow up. Periodic skin fold thickness measurements may The aim of this work is to develop an illness perception questionnaire provide inexpensive tool for the early diagnosis. High risk JDM patients for adolescents with JIA. should be screened for metabolic abnormalities, which are common in Methods: The first phase was a two-stage qualitative analysis of patients with LD. transcripts from cognitive interviews with 20 adolescents. It became Disclosure statement: The authors have declared no conflicts of clear that participants focused on their main symptom of JIA, in this interest. case pain, rather than JIA. Modifications to IPQ-R items were undertaken to devise the first version of the Pain Perception 270. HAEM OXYGENASE 1 DEFICIENCY: A MIMICKER OF Questionnaire for Young People (PPQ-YP). It was then sent to 18 CHILDHOOD VASCULITIS adolescents aged between 11 and 16 years to assess linguistic and 1 2 3 face validity. Participants were asked to think of a recent pain to Anju Gupta , Yachie Akihiro , Akshay K. Saxena , 4 1 answer the questionnaire and provide feedback on the language and Anish Bhattacharya and Surjit Singh 1 length. After further modifications, the PPQ-YP was sent to 65 patients Pediatrics, Postgraduate Institute of Medical Education and with JIA to test further psychometric properties. Research, Chandigarh, India, 2Pediatrics, Kanazawa University Results: The thematic analysis showed that episodic and unpredict- Hospital, Kanazawa, Japan, 3Radiodiagosis and 4Nuclear Medicine, able nature of JIA pain experiences meant that the existing adult Postgraduate Institute of Medical Education and Research, version of the IPQ-R did not adequately capture adolescents’ pain Chandigarh, India beliefs. Furthermore, the adolescents reported that their behaviour was determined by their pain experiences. The content analysis of Background: Haem oxygenase-1 (HO-1) deficiency is a rare genetic feedback about of the IPQ-R showed which items elicited the most disorder first described by Yachie et al in 1999. Deficiency of this POSTER VIEWING III Thursday 30 April 2015 i155

enzyme leads to extensive prooxidant stress resulting in multisystemic Disclosure statement: The authors have declared no conflicts of involvement. interest. Methods: A 20-month-old developmentally normal boy presented to us with fever of 4 weeks duration. He had history of passing cola coloured 272. HAND GRIP STRENGTH IN JUVENILE IDIOPATHIC urine for 2 days. Six months previously, he had had fever lasting for 10 days, and was found to have leucocytosis and thrombocytosis. Even ARTHRITIS AS PREDICTOR OF DISEASE ACTIVITY AND after the fever had subsided, he continued to have raised leucocyte and DISABILITY IN CLINICAL PRACTICE platelet counts. He was extensively investigated for the present episode Nevin Hammam1 and Ahmed Rashed1 of fever before being referred to us. Most investigations were negative 1Noha A.-W. Hassan, Rheumatology and Rehabilitation Department, except for urine microscopy showing subnephrotic proteinuria and Assiut University Hospital, Assiut, Egypt microscopic haematuria. Ultrasonography revealed mild hepatomegaly. CT revealed subcentimetric intra-abdominal lymph nodes. Bone marrow Background: JIA is a chronic inflammatory disease resulting in joints aspirate and trephine was normal. ANA and ANCA were negative. He arthritis and deformities in the hands and fingers. This leads to was referred to us with the suspicion of malignancy, sarcoidosis and decrease of joint mobility and strength of the hands which can lead to vasculitis. A physical examination was normal. Further investigations physical and functional hand disability and subsequent reduction in revealed a small spleen and undetectable serum bilirubin. Serum ferritin daily living activities. Despite the presence of indices to assess the was more than 2000 mg/l. Haptoglobin levels were raised despite hand function, grip strength assessment remains the strong predictor haemolysis. A direct Coomb’s test was negative. Viral serologies were of both hand and upper limb function. Hand grip strength (HGS) can be negative. What led to search of this uncommon disease was the measured quantitatively using a hand dynamometer. Although the role constellation of clinical and laboratory features which could not be of HGS in evaluating hand function in JIA has been studied, the use of explained by any one illness; to our surprise, all the manifestations could HGS as a predictor of disease activity and disability in JIA has not been be explained by HO-1 deficiency. The child was found to be explored. The aim of the study was to evaluate the HGS in JIA patients homozygous for c.130 C>T in exon 2 of the HO1 gene, confirming the using electronic hand dynamometer and to assess its relationship with diagnosis of HO-1 deficiency. Both parents were found to be JIA disease activity, disability and quality of life. heterozygous for the same mutation. Methods: Twenty-three patients with JIA (14 girls and 9 boys) Results: HO-1 is a rate-limiting enzyme catalysing oxidation of haem diagnosed according to ILAR classification criteria and 59 healthy to biliverdin, which is further converted to bilirubin by biliverdin children were enrolled in the study. The disease activity was assessed reductase. Its deficiency leads to increased haem concentrations with using Juvenile DAS (JDAS27). The Juvenile Arthritis Functionality Scale low bilirubin levels, leading to extreme oxidative stress. To the best of (JAFS) and Paediatric QOL Inventory (PedsQL) were used to assess our knowledge, this is the third child described in literature with HO-1 physical function and quality of life respectively. HGS was tested three deficiency and first such where diagnosis was made antemortem, times in each hand of every patient and control using an electronic however lack of specific therapy made our efforts futile with the patient hand dynamometer and the mean value was considered. succumbing to his illness within 3 months of diagnosis. Results: Patients with JIA showed low HGS in one or both hands Conclusion: Clinical presentation can be variable with incidentally compared with healthy children (P ¼ 0.001). Grip strength showed a picked up leucocytosis and thrombocytosis or with more severe significant inverse correlation with JDAS27 (P ¼ 0.003, r ¼ –0.591) and manifestations like intravascular haemolysis with peculiarly low with JAFS (total and after exclusion of hand component; P ¼ 0.001 and bilirubin levels, nephritis and features of systemic inflammation. All 0.002, r ¼ –0.650 and 0.608, respectively). Significant correlations these clinical features could point to an underlying autoimmune were observed between HGS and PedsQL (P ¼ 0.036). condition as was thought in this child and in the two other children Conclusion: Patients with JIA have reduced HGS when compared described previously. Asplenia or hyposplenia could be an important with healthy children. HGS may be considered as a noninvasive clue to this diagnosis and could explain significant leucocytosis and predictor of JIA disease activity and disability. Paediatric quality of life thrombocytosis. It is important for the treating physician to be aware of is adversely affected with decrease in HGS. HGS testing might be this entity and investigate accordingly. used a simple screening for disease activity in patients with JIA. Disclosure statement: The authors have declared no conflicts of interest. Disclosure statement: The authors have declared no conflicts of interest. 271. CARDIAC FUNCTION IN PATIENTS WITH JUVENILE DERMATOMYOSITIS ON FOLLOW UP 273. IN ADOLESCENT PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS, ANXIETY AND MOOD PREDICTS Biraj Parajuli1, Anju Gupta1, Manojkumar Rohit2 and Surjit Singh1 1 2 FUNCTION WHEREAS LIFE EVENT STRESSORS IN THE Pediatrics and , Postgraduate Institute of Medical OLDER ADOLESCENT PREDICTS INFLAMMATION Education and Research, Chandigarh, India Laura Hanns1, Linda Suffield1, Anna Radziszewska1, Debajit Sen2, Background: JDM is the commonest idiopathic inflammatory myo- Deborah Christie3 and Yiannis Ioannou1 pathy of childhood. While skin and muscle involvement are predomi- 1Rheumatology, University College London, 2Rheumatology, nant in acute phase, lipodystrophy and calcinosis are frequent long- University College London Hospital, 3Epidemiology & Public Health, term complications. Cardiac involvement is described in acute phase University College London, London, UK with involvement of cardiac muscles, pericardium and conduction system predominantly. Not much is known about cardiac involvement Background: It is often reported by patients and clinicians that during in long-term follow up of JDM. This study was aimed to assess the times of stress patients with inflammatory arthritis experience flares of cardiac function in patients with JDM on follow up for more than 5 disease. This is particularly prevalent during adolescence, a time of high years and compare with age and sex-matched controls. stress for many. There is increasing scientific evidence emerging that Methods: Twenty-one consecutive patients of JDM on follow up shows how stress, anxiety and depression can trigger changes to the underwent 12 lead ECG and echocardiography (ECHO; 2D and tissue immune system such as increased susceptibility to inflammation. Several Doppler). ECG was evaluated for heart rate, rhythm, P wave, PR studies have shown an association between psychological distress and interval, QRS axis, QRS duration, ST segment, QTc and T wave. ECHO worsened disease in RA in adults, yet this association has never been (by 2D and tissue Doppler) parameters including LV mass, LV mass explored in detail for patients with JIA or in a purely adolescent population. index, LA, LVEdD, RVEdD, IVSD, PWD, AO, EF, FS, E, A, E/A, IVRT, E’, Methods: 106 patients with JIA between the ages of 13 and 18 years A’ and E’/A’ were recorded. All parameters were compared with were recruited from University College Hospital, London, and gave controls and population-based norms. Data analysis was done using informed consent [median age 17 (interquartile range 2)], 50% male). SPSS statistical software (version 20.0 IBM SPSS statistics, USA). Each patient completed a questionnaire pack assessing chronic stress Results: The mean age of the enrolled cases was 16.90 4.52 years, (Coddington Life Event Scale – Adolescent Version), anxiety (State– with a range of 9–26 years. The mean interval from diagnosis to the Trait Anxiety Inventory) and depression (Short Mood and Feelings enrolment was 9.14 3.35 years, with a range of 5–16 years. Thirteen Questionnaire – Child Version). Disease activity measures explored patients had no disease activity at enrolment. ECHO parameters were the Childhood HAQ (CHAQ), ESR, CRP and swollen and limited showed high right ventricular end diastolic diameter (RVEDD), low joint counts. Data were analysed using the Spearman’s rank fractional shortening (FS) and E/E’ in cases compared with controls; correlation coefficient and the Mann–Whitney U test. but this difference did not achieve statistical significance. Results: We found that 55% of adolescents with JIA have anxiety, Conclusion: There was no significant difference in ECG and ECHO depression or life event scores over the upper limits as defined from parameters in cases of JDM compared with controls. A longer follow the population upon which these scales were validated. Increased up on a larger cohort may be useful in delineating cardiac involvement. anxiety (elevated state, trait and total anxiety scores) associated with Absence of population-based norms for tissue Doppler studies is increased CHAQ score (P ¼ 0.0149, r ¼ 0.2803). Lower mood asso- another limitation of the study. ciated with increased disability, particularly in older adolescents i156 Thursday 30 April 2015 POSTER VIEWING III

(P ¼ 0.0002, r ¼ 0.4612). However, increased life event scores asso- of uveitis starting either adalimumab or infliximab, and non-sJIA ciated with increased ESR, particularly in older adolescents patients with no history of uveitis starting a second anti-TNF, usually (P ¼ 0.0245, r ¼ 0.2831) who had significantly higher life event scores adalimumab or infliximab. (P ¼ 0.0041). There was no association with CRP or other core Conclusion: Although etanercept remains the most common biologic variables. There were no associations between subtype and disease prescribed for JIA in the UK, there has been a clear shift towards the activity or psychological parameters. use of alternative biologics as more become available. This includes Conclusion: Adolescents with JIA have a high risk of mental health use of unlicensed biologics in certain clinical scenarios, largely driven problems. This psychological risk also impacts on physical disease by disease subtype and history of uveitis. This channelling of children activity. Here we show that mood predicts level of disability, with certain disease phenotypes towards specific therapies needs to particularly in older adolescents and anxiety also predicts level of be considered carefully in future comparative effectiveness studies disability. Higher CHAQ scores could be due to patients over reporting and to guide ongoing research priorities within rheumatology. to express their distress or patients could be more anxious or Disclosure statement: H.E.F. has received honoraria, travel bursaries depressed because of level of disability. We also show that life event and educational unrestricted grants from Pfizer, AbbVie, Roche, stressors predict inflammation but only in older adolescents. This age Novartis and Schering-Plough for work unrelated to the present group experience a greater number of more stressful life events than abstract. T.R.S. has received a medical education grant from Pfizer. younger adolescents making them more susceptible to stress induced K.L.H. has received honoraria from Pfizer and AbbVie for work inflammation. Overall, this study underlines the relevance of the unrelated to the present abstract. All other authors have declared no assessment of psychological health and the importance of psycholo- conflicts of interest. gical support fully integrated into routine care of adolescents with JIA. Disclosure statement: The authors have declared no conflicts of interest. 275. PREDICTING TREATMENT RESPONSE TO ETANERCEPT IN JUVENILE IDIOPATHIC ARTHRITIS: RESULTS FROM THE BRITISH SOCIETY FOR PAEDIATRIC 274. FACTORS ASSOCIATED WITH CHOICE OF FIRST AND ADOLESCENT RHEUMATOLOGY ETANERCEPT BIOLOGIC AMONG CHILDREN WITH JUVENILE IDIOPATHIC COHORT STUDY ARTHRITIS: A COMBINED ANALYSIS FROM TWO UK 1 1 1 PAEDIATRIC BIOLOGIC REGISTERS Lianne Kearsley-Fleet , Rebecca Davies , Mark Lunt , Taunton R. Southwood2 and Kimme L. Hyrich1,3, on behalf of the British 1 1 2 Lianne Kearsley-Fleet , Rebecca Davies , Eileen Baildam , Michael Society for Paediatric and Adolescent Rheumatology Etanercept 2,3 4 5 W. Beresford , Helen E. Foster , Taunton R. Southwood , Cohort Study1 1,6 1,6 Wendy Thomson and Kimme L. Hyrich 1Arthritis Research UK Centre for Epidemiology, Manchester 1 Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Academic Health Science Centre, University of Manchester, Manchester, 2Department of Paediatric Rheumatology, Institute of 2 Manchester, Clinical Academic Department of Paediatric Child Health, Birmingham Children’s Hospital NHS Trust and Rheumatology, Alder Hey Children’s Foundation NHS Trust, University of Birmingham, Birmingham and 3NIHR Manchester 3 Institute of Translational Medicine (Child Health), University of Musculoskeletal Biomedical Research Unit, Central Manchester 4 Liverpool, Liverpool, Musculoskeletal Research Group, Institute University Hospitals NHS Foundation Trust and University of Cellular Medicine, Newcastle University, Newcastle upon Tyne, Manchester Partnership, Manchester, UK 5Department of Paediatric Rheumatology, Institute of Child Health, Birmingham Children’s Hospital NHS Trust and University of Background: Etanercept, licensed in Europe for use in children with Birmingham, Birmingham and 6NIHR Manchester Musculoskeletal JIA, is routinely prescribed after failure of other DMARDs. The Biomedical Research Unit, Central Manchester University Hospitals objectives of this study were to investigate the influence of etanercept NHS Foundation Trust and University of Manchester Partnership, on disease activity and explore factors associated with treatment Manchester, UK response in children and young people (CYP) with JIA over the initial year of treatment. Background: The management of JIA has been revolutionized by the Methods: This analysis included CYP with JIA starting etanercept in introduction of biologics. Etanercept is most often the first choice the British Society for Paediatric and Adolescent Rheumatology biologic in the treatment of JIA; however, there may be occasions Etanercept Cohort Study (BSPAR-ETN), with baseline and 1-year where etanercept is not the preferred choice, for either effectiveness or follow-up records available. Patients with a missing ILAR category safety. Understanding how biologics are being selected will help were excluded. Univariable and multivariable backward stepwise inform future practice and research. The objectives of this study were logistic regression was performed to identify factors associated with to describe patients starting first biologic therapy; describe changes in an excellent treatment response [ACR Pediatric 30 (ACR Pedi 90)) and patient characteristics over time among patients starting etanercept; achieving minimal disease activity (MDA) at 1 year. Patients who and describe patterns of second biologic therapy. stopped etanercept therapy for inefficacy were classified as non- Methods: The British Society for Paediatric and Adolescent responders; patients who stopped for remission were classified as Rheumatology Etanercept Cohort Study (BSPAR-ETN), established responders. Patients who stopped for an adverse event or unknown in 2004, and the Biologics for Children with Rheumatic Diseases reason were excluded from the model. Imputation was used to (BCRD) study, established in 2010, are ongoing prospective observa- account for missing baseline and one year disease activity measures. tional cohorts, collecting detailed information on children and young Results: A total of 496 CYP were included; 67% female, median age at people (CYP) starting biologic therapy for JIA. At start of therapy, start of etanercept therapy 11.2 years [interquartile range (IQR) 7.6– demographic and disease information is collected. Biologic-naive 13.7], disease duration at start of etanercept 3 years (IQR 2–7). One patients registered on or after 1 January 2010 starting their first child stopped taking etanercept within the first year due to remission, biologic were identified and baseline disease characteristics com- 17 stopped due to inefficacy, 9 stopped due to adverse events and 7 pared between therapies, using descriptive statistics. An additional stopped for other reasons. Median baseline juvenile arthritis DAS cohort of CYP starting etanercept before 2010 were also included to (JADAS)71 was 17 (IQR 12–24). At 1 year, this decreased to 3 (IQR 1–9; analyse changes in etanercept prescribing since initial approval. The P < 0.001). At 1 year, 77%, 72% and 39% had reached ACR Pedi 30, pathway of patients starting a second biologic was recorded in all 50 and 90, and 49% had achieved MDA. Independent predictors of patients from 1 January 2010. achieving ACR Pedi 90 at 1 year included shorter disease duration Results: Up to 26 August 2014, 931 patients were recruited starting a [odds ratio (OR) 0.91 (95% CI 0.85, 0.97)], no concurrent oral CS use first-line biologic (142 BCRD; 789 BSPAR-ETN (583 pre-2010, 206 (OR for oral corticosteroid use 0.48 [95% CI 0.29, 0.80]) and history of post-2010)). From 2010, CYP with systemic JIA (sJIA) were almost chronic anterior uveitis [OR 2.26 (95% CI 1.08, 4.71)]. Independent exclusively prescribed anakinra or tocilizumab. The choice between predictors achieving MDA at 1 year included younger age [OR 0.60 for anti-TNF therapies was largely associated with history of uveitis (5% age 9 years compared with <9 years (95% CI 0.38, 0.95)] and no etanercept vs 70% adalimumab and 73% infliximab). Only half of the concurrent oral CS use [OR for oral CS use 0.57 (95% CI 0.35, 0.93)]. patients starting etanercept received concomitant MTX compared with Conclusion: Among this real-world cohort of children with severe JIA, the other biologics (68–89%). Compared with etanercept patients pre- a significant proportion of children achieve an excellent ACR Pedi and 2010, CYP starting etanercept from 2010 had a shorter disease MDA response scores within 1 year of starting etanercept, although duration (P < 0.001), were less likely to have sJIA (P ¼ 0.007), had few clinical factors could predict this outcome. The finding of a greater lower prevalence of uveitis history (P ¼ 0.046) and were less likely to be response in younger children, and those with a history of uveitis, receiving corticosteroids (P < 0.001). A total of 161 patients were warrants further investigation and may relate to differences in disease recorded starting a second biologic after 1 January 2010. Similar phenotype, drug pharmacokinetics or adherence. stratification of these patients were seen with regard to sJIA patients Disclosure statement: T.R.S. has received a medical education grant starting either tocilizumab or anakinra, non-sJIA patients with a history from Pfizer. K.L.H. has received honoraria from Pfizer and AbbVie for POSTER VIEWING III Thursday 30 April 2015 i157

work unrelated to the present abstract. All other authors have declared 277. GROWTH DURING TOCILIZUMAB THERAPY IN no conflicts of interest. PATIENTS WITH POLYARTICULAR-COURSE JUVENILE IDIOPATHIC ARTHRITIS: 2-YEAR DATA FROM THE PHASE III CHERISH TRIAL 276. MULTICENTRE AUDIT OF DISEASE ACTIVITY ASSESSMENT IN JUVENILE IDIOPATHIC ARTHRITIS: Athimalaipet Ramanan1,2, Kamal N. Bharucha3, Hermine I. Brunner4, JUVENILE IDIOPATHIC ARTHRITIS TOPIC SPECIFIC GROUP Nicola Ruperto5, David A. Cabral4, Abraham Gedalia4, 5 5 4 1 2 2 1 Valeria Gerloni , Christian Jorgensen , Daniel J. Lovell , Flora McErlane , Gillian Armitt , Andrew Smith , Mark Friswell , 5 6 7 8 3 2 Alberto Martini , Jim Frane , Chris Wells and Fabrizio De Benedetti Helen E. Foster and Wendy Thomson 1 1 Paediatric Rheumatology, Bristol Royal Hospital for Children, Paediatric Rheumatology, Great North Children’s Hospital, 2 2 Bristol, Royal National Hospital for Rheumatic Diseases, Bath, UK, Newcastle, Arthritis Research UK Epidemiology Unit, University of 3 3 Medical Department, Genentech, South San Francisco, CA, Manchester, Manchester and Paediatric Rheumatology, Newcastle 4 University, Newcastle, UK Pediatric Rheumatology Collaborative Study Group, PRCSG, Cincinnati, OH, USA, 5Paediatric Rheumatology International Trials 6 Background: The assessment of disease activity is a key outcome in Organisation, Genoa, Italy, Consultant, Rheumatology Department, Santa Monica, CA, USA, 7Medical Department, Roche Products Ltd, JIA, of interest to clinicians, researchers and commissioners. A 8 standardized measure of disease activity would allow comparison Welwyn Garden City, UK and Department of Pediatric Medicine, between centres and clinical trial results, and enable outcome-based IRCCS Ospedale Pediatrico Bambino Gesu` , Rome, Italy commissioning of services. However, disease activity is difficult to define and measure in this heterogeneous, multidimensional group of Background: In patients with JIA, elevated IL-6 levels have been conditions with no national consensus. Little is known about the associated with low growth velocity. The efficacy of tocilizumab (TCZ), collection of disease activity-related data in the UK or the feasibility of an IL-6 receptor inhibitor, in patients with polyarticular-course JIA disease activity assessment tools in routine clinical practice. This audit (pcJIA) has been demonstrated up to 104 weeks (2 years) in the phase of current practice aims to benchmark assessment and documenta- III CHERISH trial. In CHERISH, growth was evaluated in patients with tion of disease activity across the UK. It will inform ongoing work pcJIA treated with TCZ, with data available for up to 2 years on towards deriving consensus around a standardized measure of treatment. disease activity for JIA. Methods: In CHERISH patients with active pcJIA for 6 months and Methods: A literature review of disease activity assessment tools inadequate responses to MTX received open-label (OL) TCZ intrave- informed an initial consultation process with the JIA Topic Specific nously every 4 weeks [randomly assigned 1:1 to receive 8 or 10 mg/kg Group. A range of disease activity assessment tools was identified for for body weight (BW) <30 kg or 8 mg/kg for BW 30 kg] for 16 weeks. inclusion in the audit. 14 UK Paediatric Rheumatology centres were At week 16, patients with JIA ACR30 response were randomly invited to participate. The audit tool included a retrospective case assigned 1:1 to receive placebo or to continue TCZ double-blind for 24 notes review of 15 patients using a pre-tested proforma derived from weeks. At week 40, all patients entered an OL extension and received the consultation process, and a more detailed centre review. TCZ according to BW through week 104. In patients with Tanner stage Results: 10/14 (71%) centres completed the audit with data available <4 (the subset of patients with the highest growth potential), height for 153 children (median age 12years, range 1–21). Although all centres velocity and height S.D. scores (SDS) were measured, unless patients intended to collect the majority of the single variables, there was wide were receiving the growth hormone somatotropin during the study variability in collection and documentation. (Table 1) Composite period. measures of disease activity were not routinely collected. All centres Results: From 188 patients receiving 1 dose of TCZ, 123 patients recorded data in multiple sites (JIA proforma (100%), clinic letters with Tanner stage <4 were included in the growth population (1 patient (90%), case notes (70%) and clinical and research databases (50 and received somatotropin and was excluded from the growth population). 40%)). At baseline, the growth population had a mean World Health Conclusion: Although there is consensus around important single Organization height SDS (S.D.) of 0.5 (1.2). Baseline height SDS measures of disease activity, collection and documentation is was not related to patient age or disease duration (Spearman’s rank inconsistent and unreliable. Understanding the reasons for missing correlations r ¼ 0.08 and r ¼ -0.12, respectively). For patients with data will inform future work. The variability across the UK emphasizes Tanner stage <4 at baseline and height data at year 2 (n ¼ 103), the need to include multiple centres in the ongoing consultation baseline mean height SDS increased significantly (by 0.40) from process to identify the optimal measure or measures of disease baseline to year 2 of treatment (P < 0.0001 vs baseline). At year 2, activity in JIA. The audit should be repeated following implementation 71.8% (74/103) of these patients had an increased height SDS of a standardized measure of disease activity across the UK. compared with their baseline height SDS. The mean height velocity in Disclosure statement: The authors have declared no conflicts of patients with Tanner stage <4 at baseline and height data at year 2 interest. was 6.7 (2.0) cm/year (n ¼ 103). For patients with available data at year 2(n ¼ 103), the mean daily oral CS doses (S.D.) at baseline and year 2 of treatment were 0.05 mg/kg (0.08) and 0.02 mg/kg (0.05), respectively. 276 TABLE 1. Disease activity data Conclusion: At baseline, the mean height SDS of patients with pcJIA Disease activity measure Centres intending Case notes with was below normal. The majority of patients (71.8%) who were Tanner to collect measure, % item available, % stage <4 at baseline and who received TCZ for up to 104 weeks, had Active joint count 100 87 an increased height SDS at year 2 (the end of the study). Limited joint count 100 79 Disclosure statement: K.N.B. is an employee of Genentech. H.I.B. Physician global 100 58 has acted as a consultant for Novartis, UCB, Genentech, Jansen, GSK Parent global 100 60 and Medimmune; and has participated in a Scientific Advisory CHAQ 100 58 Committee for a canakinumab programme in SJIA. N.R. has served ESR and/or CRP 100 52 on speakers’ bureaus on behalf of AstraZeneca, Novartis, BMS, Roche Pain 100 58 Uveitis 100 43 and Janssen Biologics B.V.; and has received research grants from Systemic features 90 20 Abbott, AstraZeneca, BMS, Centocor Research & Development, Eli Morning stiffness 70 30 Lilly and Company, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, JADAS 0 1.3 Regeneron, Roche, Sanofi-Aventis, Schwarz Biosciences, Xoma and 3-variable JADAS (JADAS3) 0 0 Wyeth Pharmaceuticals. D.J.L. has acted as a consultant for Minimal disease activity 0 1 AstraZeneca, Centocor, BMS, Abbott, Pfizer, Regeneron, Hoffman Inactive disease/remission 40 8 La-Roche, Novartis, UBC, Xoma and Genentech; and has served on CHAQ: Childhood HAQ; JADAS: juvenile arthritis DAS. speakers’ bureaus on behalf of Wyeth Pharmaceuticals. A.M. has i158 Thursday 30 April 2015 POSTER VIEWING III

served on speakers’ bureaus on behalf of AstraZeneca, Novartis, BMS symptoms. The role of vitamin D in FM is unclear: there is conflicting and GSK; and has received research grants from Abbott, AstraZeneca, evidence as to whether patients with FM or chronic widespread pain BMS, Centocor Research & Development, Eli Lilly and Company. J.F. have lower vitamin D levels than controls. Few controlled studies have is an employee of Genentech. C.W. is an employee of Roche. F.D.B. investigated the effect of vitamin D replacement in FM patients, and has acted as a consultant for BMS, Pfizer and Roche Pharmaceuticals; these have reported contradictory results. The aim of this study was to and has received research grants from Abbott, BMS, Pfizer, SOBI, examine the association between serum levels of vitamin D and a Novimmune, Roche Pharmaceuticals and Novartis. All other authors variety of clinical measures of FM symptoms. have declared no conflicts of interest. Methods: Patients attending a secondary care multidisciplinary FM clinic and meeting 2010 ACR preliminary diagnostic criteria and/or 1990 classification criteria had serum levels of 25(OH)-vitamin D measured as part of their routine clinical assessment. In addition patients were asked to complete questionnaires as follows: PAIN Widespread Pain Index (WPI), pain visual analogue score, GAD7 (anxiety), PHQ9 (depression), PHQ15 (somatization), FACIT-fatigue and the revised FM Impact Questionnaire (rFIQ). the Symptom Severity Score (SSS) and the tender point count were recorded by the treating physician (SSS and WPI are the components of the 2010 ACR 278. TRENDS IN LONG-TERM OPIOID PRESCRIBING IN preliminary diagnostic criteria for FM). Data were analysed using SPSS PRIMARY CARE PATIENTS WITH MUSCULOSKELETAL version 22 statistical software (IBM). Correlations between variables CONDITIONS: AN OBSERVATIONAL DATABASE STUDY were determined and corrected for age, sex, ethnicity and season. John Bedson1, Ying Chen1, Richard Hayward1 and Kelvin Jordan1 Statistical significance was set at P < 0.05. 1Primary Care and Health Sciences, Keele University, Keele, UK Results: Complete data sets were available for 146 patients. 85% of patients were female and 82% were white. Mean age was 45 years Background: 20% of adults in the UK present to primary care with a (range 16–79). 67 patients had vitamin D levels of <50 nmol/l; levels musculoskeletal condition each year. Guidelines such as those from were significantly lower in non-white patients. No significant correla- National Institute for Health and Care Excellence (NICE) advocate tions were seen between vitamin D and any clinical variables across using opioids, and musculoskeletal patients form the dominant group the whole group. When only patients with vitamin D <50 nmo/l who receive long-term opioids. In the USA there has been a (insufficient or deficient) were analysed significant correlations were 2 considerable increase in long-term opioid use. It is unclear if this seen between vitamin D and SSS (r ¼ 0.08, P ¼ 0.019), GAD7 (0.06, increase has also occurred in the UK, and whether national and 0.034), PHQ9 (0.13, 0.002) and rFIQ (0.09, 0.012). These remained international prescribing guidelines have influenced this. significant after correction for other variables as above. No correlations Methods: This was an observational database study undertaken in the were seen between vitamin D and objective or subjective measures of Clinical Practice Research Datalink (CPRD) from 2002 to 2013. pain. Patients aged 18 and over who consulted for a musculoskeletal Conclusion: We have shown small but significant correlations condition at the start of a long-term opioid episode were identified. A between vitamin D for a number of symptom domains of FM, most long-term opioid episode was defined as 90 days or more prescribed strongly with somatization, in patients with FM and low levels of medication initiated following a period of 6 months of no opioid use. vitamin D. No correlation with measures of pain was seen. The The episode ended if there was 6 months or more without such a direction of these associations is unclear. Only one small controlled prescription. Patients with cancer were excluded. Each year was study has examined the effect of vitamin D replacement on non-pain divided into quarters starting January–March 2002. The incidence of symptoms in FM and reported positive results. Larger studies are starting long-term opioid episodes was determined per quarter needed to focus on the effect of vitamin D on multiple symptom and stratified according to age, gender and type of opioid. Opioids domains in patients with FM and vitamin D insufficiency. were grouped as short or long-acting controlled or non- Disclosure statement: The authors have declared no conflicts of controlled drugs. Prescribing trends were analysed using Joinpoint interest. Regression. Results: From a total population of 5 167 159, 121 133 patients started at least one episode of long-term opioids between 2002 and 2013. The 280. THE UTILITY OF THE PAINDETECT QUESTIONNAIRE IN median episode length was 231 (interquartile range 99–681) days, with ASSESSING PAIN IN RHEUMATOID ARTHRITIS 38.2% having an episode lasting more than a year and 23.7% more Nidhi Sofat1, Abiola Harrison1 and Saqa Ahmed1 than 2 years. The number of patients starting a new episode of long- 1Rheumatology, St George’s, University of London, London, UK term opioids increased from the first quarter of 2002 (10 per 10 000 persons) to the third quarter of 2008 (15/10 000), then remained stable Background: RA is a chronic inflammatory autoimmune condition until decreasing from 2011 to 2013 (13/10 000). Those in the older age characterized by systemic inflammation targeted towards synovial group (>65) and females were more likely to start new episodes. The joints. A wide variety of immuno-modulatory drugs are now available increase in incident prescribing in 2008 coincided with the publication for treating RA e.g. MTX and biologic therapies including TNFa of NICE OA guidelines, and the decrease from 2011 with the US inhibitors. In many cases, disease-modifying therapies result in National Drug Control Policy to decrease prescribed opioid abuse. disease remission. However, despite the era of widespread use of There was a substantial increase in the prescribing of long-acting disease-modifying agents, there are significant groups of patients with controlled drugs from approximately 2% in 2002 to 16% in 2013. RA who continue to experience pain. Conclusion: The incidence of long-term opioid prescribing in the UK Methods: Our study formulated a pain assessment tool to be used in increased by 50% from 2002 to 2008 but declined from 2011 onwards. the arthritis clinic to assess feasibility of measurements including the An increase occurred at a time when guidelines advocated opioid use visual analogue scale (VAS) for pain, range 0–100 mm and for painful musculoskeletal conditions, while the decrease might reflect painDETECT questionnaires (range 0–38) to evaluate neuropathic a spill over from the US Government’s action plan to reduce features of pain in people with established RA (n ¼ 100). Clinical prescribed opioid abuse. Regulations to monitor prescribed opioids measures of disease activity [DAS for 28 joints (DAS28)], disease- use have now been actioned in the UK and further research is required modifying medication use, BMI and worst pain ever were also to determine if these are effective ways in which to promote effective recorded. Continuous data were described and analysed using and appropriate opioid prescribing. parametric statistics, with ANOVA and chi-squared tests for groups Disclosure statement: The authors have declared no conflicts of with three or more categories. interest. Results: People with RA reported relatively high pain levels, despite widespread use of disease-modifying drugs. The majority, 54%, 279. ASSOCIATION BETWEEN VITAMIN D AND MULTIPLE reported severe pain on the VAS, which identifies people with a VAS SYMPTOM DOMAINS IN FIBROMYALGIA of 54–100 mm as having the highest severity of pain. The mean DAS28 in the group was 2.09 0.96. The majority of subjects had a Priyanka Singh1, Amanpreet Singh Kahlon1, Katherine Irving1, diagnosis duration of greater than or equal to 5 years (84%), Geeta Hampson1 and Toby Garrood1 suggesting that pain was a persisting problem despite sustained use 1Rheumatology Department, Guy’s and St Thomas’ NHS Foundation of DMARDs. All participants evaluated had been stable on DMARD Trust, London, UK therapy for at least 3 months prior to completing the study and had not required a change in their treatment, or addition of corticosteroid Background: FM is a condition characterized by chronic widespread therapy during that time. Using the painDETECT questionnaire, 67% pain which in most patients is associated with other non-musculoske- of patients had unlikely neuropathic pain. A significantly high letal symptoms including fatigue, psychological disorders and somatic proportion of 28% subjects had possible neuropathic pain and 5% POSTER VIEWING III Thursday 30 April 2015 i159

had features of likely neuropathic pain by painDETECT scoring. We 1Centre for Rheumatology and 2Centre for Nephrology, Royal Free found a positive correlation between VAS and painDETECT. Of note, Hospital, London, UK the group who had likely or probable neuropathic pain also showed significantly increased pain reporting by VAS (BMI >30), had Background: Scleroderma renal crisis (SRC) is a severe complication statistically higher proportions of pain reporting (VAS 89.0 0.7) of SSc. Most SSc cases demonstrate a disease-specific ANA, for compared with subjects who had a normal BMI (VAS 45.2 21.8; example anti-RNA polymerase III, anti-fibrillarin (AFA), anti-topisome- P < 0.05). rase-1 (ATA) or ACA antibody. Previous studies have confirmed anti- Conclusion: Our findings suggest that a number of features of pain RNA polymerase III as a powerful serological predictor of SRC. We perception exist in RA, including neuropathic and sensitization developed an innovative approach to identify genetic susceptibility loci components, perhaps explaining why a subgroup of people with RA for SRC using an anti-RNA polymerase IIIþ cohort of SSc cases continue to experience ongoing pain, despite their apparent suppres- distinguished by occurrence of SRC. sion of inflammation. Methods: First we analysed SRC in a well characterized group of Disclosure statement: The authors have declared no conflicts of SSc cases followed at our centre (n ¼ 415). Informed by this, 50 interest. patients with confirmed SRC and anti-RNA polymerase IIIþ and another 50 SSc anti-RNA polymerase IIIþ that had never developed SRC were identified from our larger SSc cohort. These cases, all with 281. FACET JOINT INJECTIONS FOR BACK PAIN Northern European ancestry, were genotyped across approximately Laura Watts1 and David Grant2 one million SNPs using the Illumina Human Omni-express bead array 1Nuffield Department of Orthopaedics, Rheumatology and chip. All data underwent quality control checks for Hardy-Weinberg Musculoskeletal Sciences, Botnar Research Centre and 2Radiology equilibrium and genotyping rate in PLINK (HWE; P < 0.001 and a Department, Oxford University Hospitals NHS Trust, Oxford, UK genotyping rate of >90%). After filtering of SNPs, a logistic regression was performed in PLINK comparing patients with or Background: Injection of local anaesthetic and steroid into the facet without SRC to determine the genetic signature difference between joints can be used for both diagnostic and therapeutic purposes for these two groups of patients. chronic back pain. They are commonly performed in radiologically Results: Initial analysis confirmed a strong association between anti- þ proven degenerative facet joint disease and in our hospital, in patients RNA polymerase III and SRC with 30% anti-RNA polymerase III SSc with vertebral compression fractures, wherein successful pain relief developing SRC compared with 7% AFA, 4% ATA and 1% ACA þ can reduce the need for vertebroplasty. The effectiveness of these (P < 0.001). Moreover, in anti-RNA polymerase III cases almost all injections remains unclear. We present the results of a large cohort of SRC occurred within 18 months of disease onset, and SRC after 5 facet joint injections performed in our centre for degenerative disease, years of follow up was very rare. Thus we could define a group with compression fractures and alternative causes. SRC and another at very low risk. This dichotomy formed the basis of þ Methods: The radiological report, indication and patient pain diary our genetic analysis comparing anti-RNA polymerase III patients with from all fluoroscopy guided facet joint injections performed at our SRC history (Group A) to the control group, who had been followed for centre during the 3-year period from September 2011 to August 2014 >60 months without SRC (Group B). We performed genome-wide were retrospectively analysed. Facet joints were injected with a association study analysis on these two groups. Quality control checks combination of steroid and local anaesthetic with doses and volumes removed 2309 SNPs for missingness (GENO >0.1) and 77 122 failed determined by the operator. The sites of injection were determined minor allele frequency (MAF) filters (MAF <0.01). In total 641 489 SNPs by the site of maximal pain and tenderness, with radio-opaque were analysed. The logistic regression analysis identified a number of contrast typically used to confirm needle position. As is standard SRC associated SNPs within genes and gene regions. Top associa- 5 practice at our centre, all patients were issued with a pain diary tions were found in the complement region (P ¼ 1.66 10 ), and in 5 consisting of a visual analogue scale for pain (0–10) prior to the other genes including EPHA5 (P ¼ 1.87 10 ), GRIA3 5 5 procedure, immediately afterwards, at 1 and 2 days and at 2 weeks. (P ¼ 2.16 10 ), HECW2 (P ¼ 2.71 10 ) and CTNND2 5 They are also asked to monitor and rate their daily activities, (P ¼ 2.92 10 ). analgesic use and give an overall rating as to whether they found the Conclusion: We present a novel study using extreme phenotypes of þ procedure helpful. anti-RNA polymerase III SSc to identify genetic association of SRC in Results: 568 facet joint injections were performed over the 3-year cases that are serologically and clinically otherwise homogeneous. We period. 466 completed pain diaries were returned. Compared with pre- identified genes including catenin cadherin-associated protein delta 2 procedure score, patients had a highly significant decrease in pain (CTNND2), which is known to regulate adhesion molecules relevant to score immediately post-procedure, at day 1, day 2 and 2 weeks fibrosis. Genes identified from this analysis may have general (P < 0.001 at all time points). 68% of respondents reported that the relevance to SSc vasculopathy or other forms of hypertensive overall procedure was to some extent helpful. 51% of respondents thrombotic microangiopathy. Additional functional and genetic repli- reported that their daily activities were easier or much easier post- cation studies are needed. procedure, whereas less than 5% reported increased difficulty with Disclosure statement: The authors have declared no conflicts of daily activities. 46% reported a decrease in analgesic use. Comparing interest. data from those who underwent facet joint injection for compression 283. ENDOTHELIN RECEPTOR BLOCKADE PREVENTS fracture vs degenerative disease, no significant differences in mean DEVELOPMENT OF PULMONARY HYPERTENSION IN A change in pain scores between the two groups were observed at any MOUSE MODEL OF SCLERODERMA time point. Conclusion: We present the results of a large cohort of facet joint Emma Derrett-Smith1, Vincent Sobanski1, Sarah Trinder1, injections performed in our centre. While further prospective studies, Adrian Gilbane1, Marc Iglarz2, David Abraham1, Alan Holmes1 and with appropriate placebo/control groups and longer term follow up, are Christopher P. Denton1 needed, our patients demonstrated a highly significant improvement in 1Inflammation, Division of Medicine, University College London, pain score post-facet joint injection, and the majority felt that they London, UK and 2Pulmonary Hypertension, Actelion Pharmaceuticals derived some degree of benefit from the procedure. Ltd, Allschwil, Switzerland Disclosure statement: The authors have declared no conflicts of interest. Background: Pulmonary arterial hypertension (PAH) is an important complication of SSc that occurs in around 10% of cases. We have previously shown that a TGF-b dependent transgenic mouse strain (TbRIIÁk-fib) is susceptible to organ based pathology relevant to SSc including development of pulmonary hypertension (PH) after pharma- SCLERODERMA AND RELATED cological pulmonary endothelial injury by SU5416, a VEGF receptor DISORDERS inhibitor. In this study, we have prevented the development of PH in this mouse strain using macitentan, a novel dual ETA/B receptor antagonist recently licensed to treat PAH in CTD based upon a significant effect on morbidity and mortality in PAH. 282. DEFINING GENETIC RISK FOR SCLERODERMA RENAL Methods: SU5416, a VEGF receptor inhibitor, was administered to all CRISIS: A GENOME-WIDE ANALYSIS OF ANTI-RNA TbRIIÁk-fib transgenic (TG) mice and wild-type (WT) littermate POLYMERASE ANTIBODY-POSITIVE SYSTEMIC SCLEROSIS controls to induce endothelial injury with subsequent endothelial proliferation and PH in transgenic mice only. Mice were treated with Sandra G. Guerra1, Carmen Fonseca1, Svetlana I. Nihtyanova1, either 50 mg/kg macitentan daily by oral gavage or vehicle alone (n ¼ 8 Edward Stern1, David J. Abraham1, Aine Burns2, Mark Harber2 and for each group) either before SU5416 injection or on day 8 following Christopher P. Denton1 injection. The development of PH in each group was assessed by i160 Thursday 30 April 2015 POSTER VIEWING III

histology and immunohistochemistry of vessel architecture, in vivo 32 patients (67%); linear morphea of trunk and limbs in 4 patients haemodynamic studies and RV mass index measurements. (8.0%) and keloid/nodular morphea in 12 patients (25%). 28 out of 32 Biochemical responses to TGF-b, endothelin and VEGF stimulation patients with plaque morphea and 3 out of 4 patients with linear before and after macitentan were examined in cultured TbRIIÁk-fib morphea had limited cutaneous SSc, while 11 out of 12 subjects with lung fibroblasts. keloid/nodular morphea had diffuse cutaneous SSc (P < 0.001). There Results: Compared with WT littermates, after SU5416, all TG mice were no clear serological associations when correcting for subset. developed a prominent perivascular chronic inflammatory infiltrate and Black ethnicity, as could be expected, was prevalent in patients with smooth muscle layer hypertrophy, as previously described. RV mass keloid/nodular morphea (58% of keloid patients compared with 4% in index was elevated in TG animals receiving vehicle compared with our SSc cohort). Keloid nodules were localized on the upper chest, other groups (TG vehicle 0.29 0.007, TG macitentan 0.24 0.007, breast and upper limbs. Demographic, clinical and serological data are P < 0.05). The increase in RV systolic pressure in TG animals treated summarized in Table 1. Gene expression analysis defined key markers with SU5416 was also abrogated by macitentan (TG vehicle of matrix over expression compared with early stage or established 28.8 mmHg 0.72, TG macitentan 22.0 1.62, P < 0.001) without SSc lesional skin. any significant change in systemic arterial blood pressure in any Conclusion: This is the largest analysis of localized scleroderma in group. Treatment with macitentan after day 8 was sufficient to SSc to be presented. There are particular associations of subtypes of normalize haemodynamic consequences of SU5416 administration. localized scleroderma with subsets of SSc which are not related to There was obliterative pulmonary arteriolar occlusion in 21% of serology. Paired gene expression of keloid and non-keloid SSc skin vessels in TG mice treated with vehicle. In contrast, no vessels in will contribute to an understanding of pathogenesis of this rare but WT mice or TG mice treated with macitentan developed this important complication. histological change. Explanted TG lung fibroblasts showed an increase Disclosure statement: The authors have declared no conflicts of in proliferation and migration with upregulation of VEGF and TGF-b interest. signalling and downregulation of endothelin receptor A compared with WT littermates. Conclusion: Macitentan prevents the development of histological and 285. SYSTEMIC SCLEROSIS INPATIENT MORTALITY HAS haemodynamic PH in this mouse model of SSc. These findings NOT IMPROVED FROM 1995 TO 2011: RESULTS FROM A suggest a pivotal role for perturbed endothelin activity in the NATIONAL IRISH AUDIT OF SCLERODERMA CO- development of PH associated with altered TGF-b and VEGF MORBIDITIES signalling. Our results also validate this model as a platform for Len Harty1, Deirdre Fitzgerald2, Michael T. Henry2, John G. Ryan1 experimental therapeutic studies and provide further insight into and Sinead Harney1 pathogenic mechanisms of PAH in SSc. 1Rheumatology and 2Respiratory, Cork University Hospital, Cork, Disclosure statement: M.I. is an employee of Actelion Ireland Pharmaceuticals. All other authors have declared no conflicts of interest. Background: Despite the advent of potent immunosuppressive and vasoactive therapies it is not clear that longevity of patients with SSc 284. A STUDY OF MORPHEA IN SYSTEMIC SCLEROSIS: has improved. We sought to evaluate the age of death of SSc DEFINING LINKS BETWEEN LOCALIZED AND SYSTEMIC inpatients (inpts) relative to general inpts, the number of hospital inpt SCLEROSIS days and comorbidities in SSc patients. Methods: The Hospital In-Patient Enquiry system was evaluated from Nataliya Gak1, Emma Derrett-Smith2, Svetlana I. Nihtyanova1, 57 Irish hospitals from 1995 to 2011 for patients admitted with a Voon Ong1, Victoria S. Swale1, Cate H. Orteu1 and diagnosis of SSc. Age, length of stay (LOS), gender and indication for 2 Christopher P. Denton admission were recorded. Results are shown as totals and mean (S.D.). 1Royal Free London NHS Foundation Trust and 2Division of Trends were examined by logistic regression analysis; Mann–Whitney Medicine, University College London, London, UK U was used to compare groups. P < 0.05 was considered statistically significant. Background: Some patients with SSc develop skin features of Results: 2667 inpt admissions were reviewed; 4:1, F:M, mean age 59 localized scleroderma. One clinical subtype, keloid/nodular morphea, years (yrs; 15). On average, 157 (15) admissions occurred annually for is particularly challenging to treat and may offer insight into key SSc patients, without any annual difference (P ¼ 0.7). 146 patients died pathogenetic mechanisms. We have identified a cohort of SSc cases in hospital at an average age of 65 years (5), which did not improve with concurrent localized scleroderma and examined their clinical and annually (r2 ¼ 0.03, P ¼ 0.5; 1995–2011).SSc age of death was laboratory features and undertaken gene expression analysis to define significantly younger than age of death among general hospital inpts, the underlying pathogenic mechanism. (P < 0.0001) which has improved from 72 years in 1995 to 74 years in Methods: We examined a clinical database of 2200 patients with SSc 2011 (r2 ¼ 0.9, P < 0.0001). Male SSc inpts died significantly younger to identify all patients with a clinical or histological diagnosis of than their female counterparts [60 years (10) vs 66 years (6); localized scleroderma and SSc overlap. The demographics, clinical P < 0.01]. In contrast, men were on average 3 years younger than features and serology of these patients were examined in detail. We women at death among other hospital inpts (70 years v 73 years). SSc undertook gene expression analysis of forearm and keloid/nodular inpt LOS increased from 11 to 14 days (r2 ¼ 0.3, P ¼ 0.03). Autoimmune morphea lesional skin biopsies from six patients by RT-PCR for matrix disease (predominantly scleroderma) was the admitting diagnosis in genes including COMP and thrombospondin-1, skin biopsies from most inpts (n ¼ 945). Lung disease accounted for 383 inpt admissions patients with early or established diffuse cutaneous SSc provided a (170 infection, 62 pulmonary hypertension), CVS disease (n ¼ 397, 236 control group. limb/cardiac/cerebral ischaemic events, 51 heart failure, 32 arrhyth- Results: 49 patients (2.2%) had evidence of localized scleroderma mia), gastrointestinal disease (n ¼ 301, 18 infection), with 151 pts and SSc. Demographic and clinical data from this group were broadly admitted for rehabilitation and 120 for musculoskeletal pathologies, 89 comparable to the SSc cohort, excepting higher prevalence in females for blood disorders (52 anaemia) and 85 for renal disorders (51 failure, (female: male ratio 11:1). Limited: diffuse cutaneous SSc ratio was 2:1 19 infection). 16 pregnant patients were admitted, with two sponta- which is representative of this SSc cohort. Three subtypes of localized neous abortions and three episodes of pre-eclampsia recorded. scleroderma were prevalent in this patient group: plaque morphea in Diagnostic imaging was the most frequent principal procedure

284 TABLE 1. Demographic, clinical and serological characteristics of patients with keloid/nodular morphea and SSc Age Sex Ethnicity SSc subset Other disease Reactivity Systemic immunosuppressive treatment 52 F Black dcSSc SLE RNP MMF 53 F Black dcSSc Scl-70 MMF 51 F Black dcSSc Sarcoid Scl-70, Jo1 prednisolone 56 M Black dcSSc Psoriasis U3RNP MMF 48 F Black dcSSc U3RNP AZA 42 F Black dcSSc Scl70,Ro MTX 47 F Black dcSSc U3RNP MMF 40 F White dcSSc RNAp MMF 54 F White dcSSc Scl70,Ro AZA 46 F White dcSSc Scl70 MMF 76 F White lcSSc none MMF 39 M Asian dcSSc RNAp MMF dcSSc: diffuse cutaneous SSc; F: female; lcSSc: limited cutaneous SSc; M: male. POSTER VIEWING III Thursday 30 April 2015 i161

(n ¼ 346), followed by i.v. therapy (n ¼ 297), allied health professional Disclosure statement: A.M. was supported by the Arthritis Resarch UK intervention (n ¼ 277) oesophago-gastro-duodenoscopy (n ¼ 208), with (grant number 19465). I.P. received the Doctoral Training Partnership 62 patients undergoing limb amputation and 9 patients having kidney (ESPRC). All other authors have declared no conflicts of interest. transplants. Conclusion: Despite therapeutic advances, age of death among SSc 287. AN OBSERVATIONAL STUDY OF INTRAVENOUS inpts is not improving in contrast to unaffected inpts whose age of IMMUNOGLOBULIN THERAPY IN THE TREATMENT OF death is increasing. Furthermore SSc LOS is increasing whereas LOS GASTROINTESTINAL INVOLVEMENT IN SYSTEMIC for general inpts is decreasing. The burden of ischaemic disease SCLEROSIS among SSc inpts in particular is high and this supports the need for more therapeutics to address this aspect of SSc. Jasmin Raja1,2, Svetlana I. Nihtyanova1, Voon H. Ong1 and Disclosure statement: L.H. has received honoraria from Actelion; and Christopher P. Denton1 has received research grants from Pfizer and AbbVie. All other authors 1Centre for Rheumatology and Connective Tissue Diseases, have declared no conflicts of interest. University College London Medical School, London, UK and 2Rheumatology Unit, Department and Faculty of Medicine, University 286. PILOT STUDY OF MULTISPECTRAL IMAGING TO of Malaya, Kuala Lumpur, Malaysia MEASURE SKIN OXYGENATION IN HEALTHY CONTROLS AND PATIENTS WITH SYSTEMIC SCLEROSIS AND PRIMARY Background: IVIG is known to have beneficial effects in rheumato- RAYNAUD’S PHENOMENON logical conditions with inflammatory myopathy including myositis overlap in SSc. This study is aimed to assess the efficacy of IVIG Ian Poxon1, Jack Wilkinson2, Tonia Moore3,4, Joanne Manning3, across different aspects of internal organ involvement in refractory Mark Dickinson1, Ariane Herrick3,4 and Andrea Murray1,4 active SSc particularly the gastrointestinal system. 1Photon Science Institute, University of Manchester, Manchester, Methods: SSc patients at the Royal Free Hospital who remained 2Research and Development, 3Directorate of Rheumatology, Salford active and unresponsive to standard disease-modifying agents and Royal Hospital NHS Foundation Trust, Salford and 4Centre for subsequently received IVIG infusions were identified. Demographic, Musculoskeletal Research, Manchester Academic Health Science clinical and laboratory data were reviewed. The upper and lower Centre, University of Manchester, Manchester, UK gastrointestinal symptoms were assessed using the Reflux Disease Questionnaire (RDQ) and UCLA SCTC GIT 2.0 questionnaire. Medical Background: SSc is a multisystem CTD causing blood flow dysfunc- Research Council (MRC) Sum Score for muscle strength and modified tion in skin and internal organs. There is a drive to identify non-invasive Rodnan Skin Score (mRSS) were also assessed. Serial assessments measures of pathophysiology to facilitate clinical trials of novel drugs were undertaken at baseline prior to IVIG and post treatment. and to differentiate patients with SSc from those with primary Results: A total of 15 SSc patients (73% diffuse subset, 87% female) Raynaud’s phenomenon (PRP), which in contrast to SSc does not between March and October 2014 were consecutively recruited into this progress to irreversible tissue injury. Multispectral imaging (MSI) study. Mean (S.D.) age was 47.3 (12) years. Mean (S.D.) disease duration provides images taken at different wavelength bands allowing from onset of first non-Raynaud’s symptoms was 7 (3.9) years. Mean measurement of skin properties such as oxygenation. Our aim was duration of IVIG treatment was 2.3 years (range 3 months to 11 years), to ascertain whether MSI could be used to measure changes in with treatment frequency ranging from 6 weekly to 4 monthly. All patients oxygenation, in response to digital occlusion, in healthy controls (HCs) were receiving proton pump inhibitors, immunosuppressive agents and and patients with SSc and PRP. standard doses. compared with baseline, there was significant Methods: 17 patients with SSc, 3 with PRP and 10 HCs underwent improvement in gastroesophageal reflux disease (GERD) frequency multispectral imaging of the hand at baseline, during digital arterial mean scores (S.D.) [3.2 (1.79) and 1.93 (0.91) respectively, P ¼ 0.039]. occlusion (2 min, 200 mmHg), at occlusion release and 1 min after Significant improvement was also observed in GERD intensity mean release. Multispectral data (500–710 nm) were collected. All patients scores (P ¼ 0.021). Significant change in GIT 2.0 score from baseline gave informed consent. Data were analysed using custom software. mean score (S.D.) [1.07 (0.67) to 0.63 (0.46), P ¼ 0.003] was seen. Mean The change on release and 1 min later was compared between groups (S.D.) baseline MRC Sum Score was 51.5 (3.5) (maximal score 60), which using linear regression. Differences in overall response to the protocol increased to 56.5 (2.9) (P ¼ 0.001) at the end of the study. Baseline mean were assessed with a test of interaction in a generalized least squares and median creatine kinase level was 501.3 and 192, respectively (range model. 35–3192) with significant reduction to 112 and 77, respectively (range Results: All groups showed decreased oxygenation during occlusion 42–465, P ¼ 0.025). There was significant amelioration of mean basal from baseline (Table 1). Upon occlusion release, hyperaemic oxygena- mRSS (S.D.), 20 (13.9) to 9.14 (10) (P ¼ 0.003 after treatment). Basal tion increase was observed in all groups. The greatest decrease in mRSS assessment was undertaken at 1.6 years prior to IVIG initiation oxygenation under occlusion and largest reactive hyperaemia was in (range 3 months to 5 years), while post-treatment assessment was the HC group. The smallest decrease and smallest reactive hyper- performed at 2.7 years (range 3 months to 8.5 years). No improvement in aemia was in the SSc group. One minute after occlusion release lung function parameters, forced vital capacity and diffusing capacity of oxygenation levels were decreasing back to baseline in the HC and lung for carbon monoxide was seen. Disease duration at IVIG initiation, PRP groups but not the SSc groups. MSI was able to measure duration of IVIG therapy and SSc disease duration were not associated differences in the amount of change in oxygenation levels between with the response status at the end of the study. groups (P < 0.01). Conclusion: This study provides support that IVIG use is associated Conclusion: HC undergo significantly increased oxygenation during with improvement of clinical features in SSc patients who have been hyperaemic response and SSc groups experience a prolonged return refractory to other immunosuppressive therapies. This approach also to baseline; both may indicate structural vessel changes in patients suggests a specific potential benefit for immunomodulation in with SSc. MSI is able to detect differences in oxygenation changes established gastrointestinal complications. between groups implying sensitivity to change and is a suitable Disclosure statement: The authors have declared no conflicts of technique for skin oxygenation measurement. interest.

286 TABLE 1. Mean skin tissue oxygenation measurements Group Baseline Oxygenation under Oxygenation change Oxygenation change 1 min oxygenation occlusion on release of occlusion post occlusion (1 min-release) (release-occlusion) Healthy, median (IQR) 0.28 (0.06 to 0.56) 1.32 (–1.50 to 1.14) 3.5 (3.3 to 3.5) 0.9 (–1.1 to 0.6) PRP, median (IQR) 0.41 (0.32 to 0.50 0.87 (–0.93 to 0.66) 2.5 (2.0 to 2.9) 0.5 (–0.7 to 0.3) Limited SSc, median (IQR) 0.63 (0.22 to 1.04) 0.70 (–1.06 to 0.51) 2.0 (0.5 to 2.2) 0.2 (-0.2 to 0.4) Diffuse SSc, median (IQR) 0.52 (–0.07 to 0.88) 0.77 (–1.36 to 0.51) 2.2 (1.1 to 2.3) 0.1 (–0.1 to 0.7) IQR: interquartile range; PRP: primary RP. i162 Thursday 30 April 2015 POSTER VIEWING III

288. INTERLEUKIN-31 IS ELEVATED IN DERMAL has been shown to affect the clinical course and outcome of the INTERSTITIAL FLUID IN SYSTEMIC SCLEROSIS AND MAY BE disease. Herein, we aimed to define the differences in clinical A KEY MEDIATOR OF ITCH IN BOTH DIFFUSE AND LIMITED characteristics and organ damage between patients with juvenile- CUTANEOUS DISEASE onset (jo-SLE) and adult-onset (ao-SLE) SLE followed up in two tertiary referral centres. Sara Zafar1, Bahja A. Abdi1, Fiona Xing1, Oseme Etomi1, 1 1 1 Methods: This analysis included 935 patients 846 of whom attended Charlotte Wong , David Abraham , Christopher P. Denton and the lupus outpatient clinic at Istanbul faculty of medicine between 1975 Richard J. Stratton1 1 and May 2012 and 89 of whom were followed in the paediatric Department of Inflammation, Centre for Rheumatology and rheumatology outpatient clinic at Cerrahpas a Faculty of Medicine Connective Tissue Diseases, Royal Free Hospital, London, UK between 2004 and 2013. The data presented were the cumulative clinical and serological manifestations throughout the follow-up Background: Severe, intractable pruritus is a debilitating symptom in period. Seven hundred and nineteen (76.9%) patients with ao-SLE approximately 40% of SSc cases. It has been particularly associated and 216 (23.1%) patients with jo-SLE were examined. Demographic with severe diffuse skin disease and resolution often coincides with characteristics, clinical features, autoantibody profiles and damage clinical improvement in cutaneous sclerosis. Resistance of itch to data [Systemic Lupus International Collaborating Clinics (SLICC) treatment with classical anti-histamine based-therapy makes it damage index] were compared between the groups. especially challenging. The pathophysiology of itch is complex, Results: Comparison of demographics revealed significant differences involving several immuno-neurological factors. One novel cytokine, in age at onset (13.5 3.5 vs 34 11.3 years) and duration of disease IL-31, produced by dermal mast cells and most notably, differentiated þ (86.5 96.2 vs 111.6 83.9 months) between juvenile and adult activated CD4 T helper 2 cells, has been implicated in mediating groups respectively (P < 0.05). Of clinical symptoms, photosensitivity allergy and atopy. Studies have demonstrated elevated serum IL-31 (71.6 vs 56.5%), malar rash (73.6 vs 45.6%) and oral ulcers (23.1 vs and upregulated IL-31 mRNA, in patients with severe itch due to 15.4%) were significantly more frequent in jo-SLE (P < 0.05). As was chronic dermopathies such as atopic eczema, allergic contact previously reported, renal involvement was significantly more pre- dermatitis and nodular prurigo. In some cases, IL-31 levels correlated valent in the jo-SLE affecting 53.2% of the patients compared with with disease activity. Studies of transgenic mice have suggested IL-31 patients with ao-SLE (38.9%; P < 0.05). Autoimmune haemolytic induces severe pruritus and serum levels correlate with scratching anaemia (AIHA) did also occur more often in the jo-SLE (33.3 vs behaviour. In this study, we explore the role of IL-31 in the 9.5%, P < 0.05) whereas reverse was true for pleuritis (11.6 vs 18.4%, pathophysiology of itch in patients with SSc and consider the cytokine P < 0.05). Of the autoantibodies, a higher frequency of anti-dsDNA a novel target for therapeutic modulation. (78.7 vs 69%), anticardiolipin IgG (31.9 vs 21%) and IgM (36.6 vs Methods: IL-31 levels in dermal blister-fluid and serum samples were 19.3%) were observed in the jo-SLE group. However, there were measured using ELISAs in a cohort of SSc cases and healthy controls. significantly more patients with anti-Sm positivity in ao-SLE (19.6 vs SSc cases with pruritus were asked to complete the standardized 5D- 10.2%, P < 0.05). According to the SLICC damage index, renal Pruritus questionnaire to enable quantitative analysis of itch severity. RT- damage was significantly more frequent in the jo-SLE (43%) than the PCR was employed to determine IL-31 and IL-31 receptor expression, ao-SLE (17.5%, P < 0.05). However, damage in musculoskeletal using messenger RNA extracted from dermal keratinocytes. Flow system, namely avascular necrosis was more prominent in the ao- cytometry will be performed to analyse intracellular IL-31 expression SLE (30 vs 15.8%, P < 0.05). and clinical correlation will be undertaken, to evaluate the relationship Conclusion: Our study confirms that clinical and serological differ- between itch severity, disease characteristics and IL-31 levels. ences exist between jo-SLE and ao-SLE. jo-SLE was associated with a Results: IL-31 expression was significantly increased in the dermal higher frequency of renal involvement and damage. We also report a blister-fluid of some of the 26 SSc cases, with a mean IL-31 higher frequency of cutaneous symptoms, oral ulcers, AIHA and anti- concentration 125.7 pg/ml vs 2.3 pg/ml in the 15 healthy controls dsDNA positivity in the jo-SLE. As renal involvement is a major (Z ¼ -2.54, P ¼ 0.006). Subgroup analysis revealed that the 12 limited predictor of prognosis and outcome, this study highlights the cutaneous SSc cases in this study had a mean interstitial fluid IL-31 of importance of awareness of the age of onset of SLE and supports 80.1 pg/ml, compared with a mean of 164.8 pg/ml in the 14 diffuse the necessity of vigilant follow up of this subgroup. cases (P > 0.05). In addition, 90 serum samples were analysed for IL- Disclosure statement: The authors have declared no conflicts of 31 concentration; a mean of 196 pg/ml was found in the 27 healthy interest. controls, compared with 1914 pg/ml in the 63 SSc patient samples, with a trend to statistical significance (Z ¼1.64, P ¼ 0.05). Preliminary data havw demonstrated a 3.7-fold increase in IL-31 receptor gene 290. LONG-TERM OUTCOME OF TREATMENT WITH expression between SSc and control RNA. MYCOPHENOLATE MOFETIL FOR LUPUS NEPHRITIS Conclusion: Together, these results suggest that IL-31 may be 1,2 2 2 increased in SSc and that this difference is especially seen in dermal Caroline Gordon , Philip R. Harvey , Samaresh Mazumdar , Chee- Seng Yee1,3 and Peter Hewins4 interstitial fluid. This makes IL-31 a key candidate mediator for the 1 2 intractable itch that may be a hallmark of active SSc skin disease and Rheumatology, University of Birmingham, Rheumatology, Sandwell 3 may represent a novel therapeutic target. Furthermore, the IL-31 axis and West Birmingham Hospitals NHS Trust, Rheumatology and 4 may play a role in other aspects of the pathophysiology of SSc; thus, Nephrology, University Hospital Birmingham NHS Foundation Trust, further evaluation is warranted. Birmingham, UK Disclosure statement: The authors have declared no conflicts of interest. Background: MMF is increasingly being used as an alternative to CYC for induction and maintenance therapy in LN. However, there are few long-term outcome data. The aim of this audit was to assess the efficacy of MMF on renal outcomes over 5 years and to compare the results with non-MMF regimes. SYSTEMIC LUPUS ERYTHEMATOSUS Methods: Lupus patients with biopsy-confirmed LN without previous AND ANTIPHOSPHOLIPID SYNDROME CYC or MMF use in the preceding year and no prior rituximab use were assessed. Data were collected from medical records, biopsy reports and electronic laboratory data. Patient groups were defined as MMF or non-MMF (mostly CYC). Patients were analysed on the basis 289. COMPARISON OF DISEASE CHARACTERISTICS AND of intention to treat. The primary endpoint required all three of: ORGAN DAMAGE IN PATIENTS WITH JUVENILE AND ADULT- reduction of proteinuria (<0.5 g/24 h or ACR<30 mg/mmol) and stable ONSET SYSTEMIC LUPUS ERYTHEMATOSUS IN A LARGE creatinine (normal or <110% baseline) without treatment failure (new COHORT FROM TURKEY immunosuppressive, end-stage renal failure or death). Secondary outcome measures included serology, steroid dose, proteinuric flare Bahar Artim-Esen1,O¨ zgu¨ r Kasapc¸ opur2, Sezgin Sahin2, and renal function. Kenan Barut2, Ahmet Omma1, Yasemin Sahinkaya1, Sevil Kamali1, Results: Ethnicity and biopsy class were comparable between groups Lale Ocal1 and Murat Inanc1 consisting of 46 patients each in MMF and non-MMF groups, with 1Department of Internal Medicine, Division of Rheumatology, Istanbul median follow up of 5 years. Primary endpoint was achieved by 74% in University, Istanbul Faculty Of Medicine and 2Department of MMF and 48% in non-MMF group (P ¼ 0.015). Achievement of Paediatrics, Division of Rheumatology, Istanbul University, prednisolone dose 10 mg without treatment failure was 78% in the Cerrahpas a Faculty Of Medicine, Istanbul, Turkey MMF and 42% in the non-MMF group (P ¼ 0.0005). In MMF group, 8/ 32 (25%) patients following response had a proteinuric flare compared Background: SLE is a multisystemic disease that may cause a broad with 11/20 (55%) in the non-MMF group, but the flare occurred earlier spectrum of clinical and immunological manifestations. Age at onset in MMF group (median 16.5 vs 21 months). Only 1/11 in non-MMF POSTER VIEWING III Thursday 30 April 2015 i163

group had a second proteinuric flare compared with none in MMF weeks gestation. One-off measurements of systemic resistance were group. The median baseline estimated glomerular filtration rate (eGFR) taken in non-pregnant women with SLE (n ¼ 34). was >80 ml/min per 1.73 m2 in both groups. Abnormal renal function Results: Diastolic blood pressure was higher in the SLE cohort at 17 was observed at baseline in 7 (17%) MMF and 9 (21%) non-MMF weeks gestation compared with healthy pregnant controls (P < 0.05). patients, of which 6 (86%) in the MMF group and 7 (78%) in the non- PWV was reduced from 16 to 22 weeks of pregnancy in the SLE cohort MMF group returned to normal within median of 3 months for both then gradually increased thereafter (ANOVA; P < 0.04). A similar non- groups. The one MMF patient whose eGFR did not improve was on significant pattern was seen in the healthy pregnant group. No AZA due to side effects on MMF. Of the two non-MMF patients who differences in PWV were defined between study groups at any failed to improve, one required haemodialysis. Of the patients with matched gestation. SI was unchanged across pregnancy in both normal baseline renal function, 4 (12%) patients in each group cohorts. In pregnant SLE cases, SI was lower than their non-pregnant deteriorated; median time to deterioration 9 months in the MMF and counterparts at 17 (P < 0.04) and 22 weeks gestation (P < 0.03). 2.5 years in the non-MMF group. There was one death in each group, Uterine artery Doppler indices in pregnant SLE patients were equal to both within 6 months of biopsy. healthy controls. No differences in gestation at delivery or individua- Conclusion: Over 5 years, MMF appears to be more effective than lized birthweight ratio were recorded between study groups. non-MMF in LN. This analysis supports the use of MMF in the Conclusion: In this study, women with SLE adapted to pregnancy as treatment of LN for induction and maintenance. effectively as their non-SLE counterparts, suggesting that pregnancy Disclosure statement: C.G. has received consultancy payments from in cases of mild/controlled SLE may be under less vascular Aspreva/Vifor Pharma, BMS, GSK, MedImmune, Roche and UCB; has compromise than previously thought. served on speakers’ bureaus on behalf of GSK and UCB; and has Disclosure statement: H.K. has received research funding from received an unrestricted educational grant for research from Aspreva/ SPARKS. All other authors have declared no conflicts of interest. Vifor Pharma. C.Y. has received consulting fees from Crysalis. All other authors have declared no conflicts of interest. 293. ALTERATIONS IN B CELL SUBSETS AND BAFF LEVELS IN AUTOIMMUNE RHEUMATIC DISEASES TREATED WITH B 291. LUPUS-LIKE AUTOIMMUNITY AND STILLBIRTH CELL DEPLETION THERAPY RITUXIMAB Hannah Kither1, Edward Johnstone1, Ian Bruce2,3, Clare Tower1 and Pamela M. K. Lutalo1,2, David D’Cruz1 and Jo Spencer2 Ian Crocker1 1Louise Coote Lupus Unit, Guy’s and St Thomas’ Hospitals NHS 1Fetal and Maternal Health, 2Arthritis Research UK Centre for Foundation Trust and 2Peter Gorer Department of Immunobiology, Epidemiology, University of Manchester and 3The Kellgren Centre for King’s College London, London, UK Rheumatology, Manchester Academic Health Science Centre, Manchester, UK Background: SLE and granulomatosis with polyangiitis (GPA) are autoimmune diseases which develop secondary to immune self- Background: The prevalence of SLE in pregnancy is 0.05%. Women tolerance failure. Both diseases are characterized in part by the with SLE have a 3.6% chance of their pregnancies ending in stillbirth. production of pathogenic autoantibodies. Although they are different SLE has a prolonged subclinical phase, characterized by autoantibody clinically, genetically and immunologically, SLE and GPA may be production. Currently many stillbirths remain unexplained. It is there- treated successfully with rituximab, an anti-CD20 mAb. The timing of B fore plausible that some idiopathic stillbirths can be attributed to cell repopulation post-rituximab may differ in these autoimmune undiagnosed SLE or lupus-like autoimmunity, before these women diseases and may be associated with serum factors, such as B-cell became pregnant. activating factor (BAFF), which promotes B cell survival or with Methods: We performed a provisional search of local GP data using characteristics of specific B cell subsets. FARSITE (NorthWest EHealth). Search terms were derived from a Methods: A prospective longitudinal study of 12 SLE and 12 GPA READ code dictionary, mapping terms for live-birth, stillbirth and SLE. patients pre-rituximab and at set intervals post-rituximab was Differences between groups were analysed by z test. conducted. Demographic, clinical and laboratory data were obtained Results: Our FARSITE search of 630 308 individuals yielded 23 603 with comparison with healthy controls. Flow cytometry analysis of pregnancies (556 stillbirths and 23 047 live births).The prevalence of transitional B cell, naive mature B cell and memory B cell subsets was SLE was significantly exaggerated in the stillbirth compared with live- conducted in experiments staining isolated peripheral blood mono- birth cohort [7.3% (n ¼ 41) vs 3.0% (n ¼ 706), P < 0.0002]. The odds nuclear cells with antibodies to CD19, IgD, CD27, CD24 and CD38. ratio for SLE and stillbirth was 2.41 (95% CI 1.73–3.33, P < 0.0001). The expression of a4b7 integrin by B cell subsets was analysed. Applying the UK background prevalence of stillbirth at 0.05%, this Plasma BAFF levels were measured by ELISA at baseline, 3 months implies that 6.8% of all stillbirths (explained or otherwise) are SLE and 6 months post-rituximab. Statistical analysis was done using related. Moreover, removing the stillbirth prevalence in established GraphPad Prism version 5. SLE (3.6%), this leaves a conservative estimate that 3.2% of all Results: B cells were found to repopulate the blood earlier after stillbirths may result from currently undiagnosed SLE. rituximab in some SLE patients compared with GPA. There was no Conclusion: Women who suffer a stillbirth are more likely to develop difference between the pre-rituximab CD19þ B cell percentage of total SLE than their live-birth counterparts, with the potential for undiag- lymphocytes in SLE and GPA (P ¼ 0.37); however, at 3 months and 6 nosed SLE to be a stillbirth cause. We hope that nationwide months post-rituximab SLE patients had a greater population of confirmation, using the Clinical Practice Research Database (with full peripheral blood CD19þ B cells compared with GPA patients (P ¼ 0.02 time/event analysis), will be possible for these provisional findings, and P ¼ 0.001, respectively). Early repopulation was found to be perhaps justifying antenatal screening for SLE for stillbirth prevention. independent of serum factors, but was related to the expression of Disclosure statement: H.K. has received research funding from a4b7 integrin by subsets of B cells. a4b7 integrin expression by SPARKS. All other authors have declared no conflicts of interest. transitional B cells, naive mature B cells and memory B cells was significantly lower in SLE compared with GPA pre-rituximab (P ¼ 0.0001, P ¼ 0.0003, P ¼ 0.0008 and P ¼ 0.0005, respectively). A 292. CHARACTERIZING PREGNANCY VASCULAR CHANGES separate analysis revealed significantly lower a4b7 integrin expression IN SLE in the early repopulation group, defined as B cell count>5 cells/ml3 Hannah Kither1, Louise Stephens1, Ian Bruce2,3, Clare Tower1 and months post-rituximab, compared with SLE patients who repopulated Ian Crocker1 the peripheral B cell pool later (P ¼ 0.004, P ¼ 0.004 and P ¼ 0.003, 1Fetal and Maternal Health, University of Manchester, 2The Kellgren P ¼ 0.7, respectively). Plasma BAFF levels were elevated in SLE and Centre for Rheumatology, Manchester Academic Health Science GPA pre-rituximab compared with HC (P ¼ 0.008 and P ¼ 0.001, Centre and 3Arthritis Research UK Centre for Epidemiology, respectively), with a rise in BAFF levels detected in SLE 3 months University of Manchester, Manchester, UK post-rituximab (P ¼ 0.006) but no difference in SLE 6 months post- rituximab (P ¼ 0.25). Plasma BAFF levels did not change significantly in Background: Patients with SLE are at increased risk of pregnancy the GPA cohort post-rituximab. Plasma BAFF levels were positively complications and hypertension and vascular stiffness outside of correlated with percentage transitional B cells (r ¼ 0.44, P ¼ 0.04). pregnancy. This study has defined changes in the maternal vascu- Conclusion: There may be an association between the early lature, systemically and locally within the uterus, in SLE-affected repopulation of the peripheral blood B cell pool, a4b7 integrin pregnant women (n-65) and healthy pregnant controls (n ¼ 32). expression by subsets of B cells and rise in BAFF levels in a cohort Methods: Pulse wave velocity (PWV) and small/large artery stiffness of SLE patients. (SI/RI) were recorded by arteriography and PulseWave plethysmo- Disclosure statement: D.P.D. has received honoraria from graphy, respectively. Brachial blood pressure and uterine artery GSK, Roche and Lilly. All other authors have declared no conflicts of Doppler resistance were likewise investigated at 17, 22, 28 and 36 interest. i164 Thursday 30 April 2015 POSTER VIEWING III

294. THE CHALLENGE OF ACHIEVING COMPLETE by British Isles Lupus Assessment Group (BILAG) 2004 for SLE REMISSION: A 32-YEAR RETROSPECTIVE ANALYSIS OF A patients and DAS for 28 joints for RA patients. LUPUS COHORT Results: Siglec-1 was found significantly higher in SLE and RA 1 2 patients than in HCs (P ¼ 0.03; ANOVA test). However, no significant Carmen Medina-Quin˜ ones , Lucı´a Ramos-Merino , Pablo Ruiz- difference was found between RA and SLE siglec-1 expression. In SLE Sada3 and David A. Isenberg4 1 2 patients, siglec-1 was found significantly higher in patients with high Rheumathology, Ramo´ n y Cajal Hospital, Madrid, Internal BILAG score (n ¼ 6) than those with low BILAG (n ¼ 17, P ¼ 0.0002; Medicine, Complejo Hospitalario A Corun˜ a, La Corun˜ a, 3Internal 4 Mann–Whitney test). Moreover, siglec-1 expression significantly Medicine, Hospital de Basurto, Bilbao, Spain and Rheumathology, correlated with levels of autoantibodies in SLE patients (P ¼ 0.0175, University College London Hospital, London, UK r ¼ 0.634; Spearman); the number of autoantibody positivity was associated with higher siglec-1 expression on monocytes. Although Background: SLE is an unpredictable disease with many periods of the BILAG score significantly correlated with percentage of PB in SLE exacerbations and remissions. There are various methods to measure patients’ blood (P ¼ 0.008, r ¼ 0.681; Spearman R), we found no disease activity, but there is no an agreement about the optimal criteria significant correlation between PB numbers or other cell subsets and for SLE remission. The principal endpoint of this study was to identify the siglec-1 levels on monocytes. Interestingly, CD64 on monocytes was number of lupus patients achieving a complete remission (absence of also upregulated in SLE and significantly correlated with siglec-1. clinical and serological features and without therapy for 3 years) in a Conclusion: Monocyte siglec-1 expression level as a measure of type single cohort followed for a period of up to 32 years. The secondary I IFN activity correlated with the disease activity and the number of endpoint was to assess patients in clinical but not serological remission positive autoantibodies in SLE. However, it does not explain the [serologically active, clinically quiescent disease—Student Adaptation to characteristic changes in B cell differentiation. Moreover, it does not College Questionnaire (SACQ)] and serological remission only. We also act as a disease-specific marker since it was invariably high in the evaluated the factors associated with complete remission. active state of both diseases. Methods: This observational and retrospective study included lupus Disclosure statement: The authors have declared no conflicts of interest. patients who were followed up in the University College Hospital from January 1978 until December 2010 for a minimum period of 3 years. Complete remission was defined as a period of at least 3 years with 296. A STUDY OF THE INFLUENCE OF ETHNICITY ON clinical inactivity (BILAG scores of C, D or E only) and normal SEROLOGY AND CLINICAL FEATURES IN LUPUS laboratory tests (no antibodies or dsDNA and normal complement 1 2 levels) and being off-treatment with corticosteroids and immunosup- Sandra A. Morais and David A. Isenberg 1Internal Medicine, ULSM – Hospital Pedro Hispano, Matosinhos, pressants. Antimalarials and NSAIDs were allowed. 2 Results: Of the 532 eligible patients, 77 patients (14.5%) achieved Portugal and Centre for Rheumatology, Department of Medicine, complete remission for at least 3 years, and 23 (4.3%) achieved University College London Hospitals, London, UK complete remission for a minimum period of 10 years. Ten of these 77 patients were subsequently lost to follow up, and interestingly flares Background: SLE is an autoimmune rheumatic disease with diverse occurred subsequently in 15 of the 67 remaining patients (22.4%). clinical and immunological manifestations. Its pathogenesis and Three patients relapsed after the tenth year of remission. Forty-five expression are influenced by genetic, environmental or socio- (8.5%) patients fulfilled the requirement for SACQ, and 66 (12.4%) demographic factors. This multiplicity helps to explain the variability patients achieved only serological remission. Achieving remission is observed in the expression of the disease, not only between negatively influenced by renal (P < 0.001), neurological (P ¼ 0.002) and individuals, but also between ethnic groups. Our objectives were to cardiopulmonary involvement (P < 0.001). Patients who went into review the influence of ethnicity on the serology and clinical expression complete remission were older at the time of diagnosis (P < 0.001) in lupus patients, in a single cohort over a 36 year follow-up period. and had a longer disease duration (P < 0.001). Methods: An audit of all SLE patients followed up long term at Conclusion: We found that 14.5% of lupus patients achieved a University College London Hospitals between January 1978 and complete remission after 3 years. However, relapses may continue to December 2013 was performed. Demographic, clinical and serological occur even beyond 10 years of remission. Long-term monitoring data were collected and reviewed. Standard methods were used for strategies are needed for better control of lupus activity. Factors such laboratory testing. Descriptive results are presented as frequencies or as renal, cardiopulmonary and neurological involvement did not favour mean (S.D.). Student’s t-test and Mann-Whitney U test were used for the achievement of complete clinical remission. Our findings confirmed continuous variables, and the chi-squared and Fisher’s exact test were that those who had an increased probability of complete remission used for categorical variables. Values of P < 0.05 were considered were older at the time of diagnosis and had longer disease duration. statistically significant. Disclosure statement: The authors have declared no conflicts of interest. Results: A total of 624 SLE patients were studied. 571 were women [91.5%; mean age at diagnosis 29.0 (6.5) years] and 53 men [8.5%; mean age 29.4 (15.3) years]. Ethnically, 369 patients were Caucasian, 295. FLOW-BASED CELL-SPECIFIC INTERFERON 135 were Afro-Caribbean, 73 were South Asian, 26 were Chinese and SIGNATURE AS A BIOMARKER IN SYSTEMIC LUPUS 21 were of other ethnicities (Table 1). South Asian and Chinese ERYTHEMATOSUS patients developed the disease younger than Caucasians or Afro- Caribbeans (P ¼ 0.00001–0.038). The Caucasian group was signifi- Alaa A. A. Mohamed1,2, Yasser M. El-Sherbiny1,2, Md Yuzaiful Md cantly associated with the presence of rash and photosensitivity. In Yusof1,2, Edward M. Vital1,2 and Paul Emery1,2 contrast, non-Caucasian patients had more alopecia and renal 1Leeds Institute for Rheumatic and Musculoskeletal Medicine, involvement. Afro-Caribbeans had the highest prevalence of anti-Sm University of Leeds and 2NIHR Leeds Biomedical Research Unit, antibodies, and both they and the Chinese patients had a higher Leeds Teaching Hospitals NHS Trust, Leeds, UK prevalence of anti-Ro and anti-La antibodies (P ¼ 0.001–0.044). Interestingly, anti-RNP antibodies and low C3 presentation were Background: Type I IFNs have been confirmed to play a pivotal role in significantly associated with being non-Caucasian; the latter was the pathogenesis of SLE and RA. IFN activity is usually monitored commonly found in the Chinese patients (P ¼ 0.001–0.036). Curiously, using a whole blood signature of IFN-responsive genes. However, Chinese and Afro-Caribbeans with rash and photosensitivity more these signatures do not correlate with disease activity and do not commonly had low C3 compared with the Caucasians. Rash, joint and predict the response to anti-IFN therapy. This may be because the IFN renal involvement was significantly associated with the presence of response varies in different cell populations whose frequency varies in anti-ENA in Afro-Caribbeans. In addition, there was an association of different disease states. We therefore sought a cell-specific IFN joint and renal involvement with anti-Ro and anti-La antibodies in signature using surface expression of the IFN response protein, siglec- Chinese patients. Caucasians with renal involvement or thrombocyto- 1 (sialoadhesin, CD169), which represents type I IFN activity on penia were significantly associated with the presence of lupus monocytes. B cells are involved in both diseases and have been target anticoagulant. of therapy by different biologics. Changes in B cell subsets [especially Conclusion: The key findings in this audit of ethnic differences in an plasmablast (PB) expansion] are associated with disease activity. SLE cohort followed for up to 36 years were that South Asian and Hence, we investigated the correlation of different B cell subsets with Chinese patients developed the disease younger then Caucasians and the level of siglec-1 in RA and SLE patients. Afro-Caribbean. Anti-ENA antibodies were showed to be more Methods: Peripheral blood was collected from 27 SLE patients, 18 RA prevalent in the Afro-Caribbeans, and the disease was commonly patients and 5 healthy controls (HCs) and was analysed for the level of accompanied by low C3 in Chinese patients. Renal involvement was siglec-1 expression on monocytes as well as for the numbers of naı¨ve, more frequent in non-Caucasians and frequently associated with anti- memory and PB B cell subsets using multiparameter flow cytometry ENA antibodies in Afro-Caribbeans. Understanding the influence of using panels including CD19, CD27, CD38, CD3, CD4, CD8, CD16, ethnicity in disease expression facilitates an individualized approach to CD14, CD56, CD64, CD69 and CD169. Disease activity was measured risk assessment, management and monitoring of SLE. POSTER VIEWING III Thursday 30 April 2015 i165

296 TABLE 1. Demographic, serological and clinical characteristics of SLE patients per ethnic group Ethnic group Caucasian Caucasian South Asian Chinese P-value Patients, n (%) 369 (59.1) 135 (21.6) 73 (11.7) 26 (4.2) Age at diagnosis, mean (S.D.) 30.6 (13.2) 29.1 (10.8) 22.9 (10.8) 25.1 (10.8) Rash, % 70.9 52.6 0.0002 Photosensitivity, % 49.2 16.7 35.6 0.039–0.0001 Alopecia, % 16.0 35.6 34.2 <0.001 Joint involvement, % 85.8 95.9 0.032 Renal involvement, % 24.1 38.8 46.6 53.8 <0.01 Anti-Smith, % 9.5 32.8 15.7 0.001–0.012 Anti-Ro, % 32.2 51.1 30.4 61.5 0.001–0.044 Anti-La, % 11.7 19.8 10.1 30.8 0.011–0.026 Anti-RNP, % 20.3 47.3 33.3 0.001–0.026 Low C3, % 38.9 52.2 52.8 80.8 0.001–0.036 Rash and anti-Smith, % 9.2 27.9 10.9 0.0002–0.035 Rash and anti-RNP, % 19.2 48.5 0.0001 Rash and anti-Ro, % 33.0 50.0 60.0 0.011–0.048 Rash and anti-La, % 12.6 23.5 0.034 Rash and low C3, % 36.9 56.5 80.0 0.0016–0.0038 Photosensitivity and low C3, % 35.8 90.9 0.0004 Alopecia and low C3, % 40.7 66.7 72.0 100 0.011–0.016 Joints and anti-Smith, % 9.7 31.6 14.9 0.0001–0.014 Joints and anti-RNP, % 19.6 46.5 33.3 0.0001–0.022 Joints and anti-Ro, % 31.9 48.2 30.3 56.5 0.0023–0.043 Joints and anti-La, % 11.1 21.1 10.6 30.4 0.011–0.042 Joints and low C3, % 38.1 51.7 51.5 82.6 0.0001–0.043 Renal and anti-Smith, % 11.2 37.3 0.0004 Renal and anti-RNP, % 18.0 49.0 0.0002 Renal and anti-Ro, % 36.0 24.2 64.3 0.0001–0.018 Renal and anti-La, % 7.9 28.6 0.041 Renal and LAC, % 23.3 7.8 0.022 Thrombocytopenia and LAC, % 35.2 7.1 0.049 LAC: lupus anticoagulant.

Disclosure statement: The authors have declared no conflicts of results. This may have been due to peer support and goal setting. interest. Increased group attendance appeared to affect the outcomes in all areas except fatigue severity. A larger scale study would need to be carried out to investigate this further. 297. IMPACT OF A FATIGUE AND ACTIVITY MANAGEMENT Disclosure statement: The author has declared no conflicts of interest. EDUCATION PROGRAMME ON INDIVIDUALS WITH SYSTEMIC LUPUS ERYTHEMATOSUS 298. EARLY SYMPTOMS IN SYSTEMIC LUPUS 1 Ruth O’Riordan ERYTHEMATOSUS: CAN THEY BE USED TO PREDICT 1 Occupational Therapy, St James’s Hospital, Dublin, Ireland DIAGNOSIS?

1,2 1 1,2 Background: Fatigue is one of the most prevalent symptoms of SLE Frances Rees , Michael Doherty , Peter Lanyon , 3 1 4 affecting up to 90% of individuals, even when the disease is in Graham Davenport , Weiya Zhang and Matthew Grainge 1 remission. Previous studies have shown that up to 50% of individuals Division of Rheumatology, Orthopaedics and Dermatology, with SLE consider fatigue to be their most disabling symptom. University of Nottingham, 2Rheumatology, Nottingham University Methods: Three Fatigue and Activity Management (FAME) pro- Hospitals NHS Trust, Nottingham, 3Arthritis Research UK Primary grammes were run from January 2013 to September 2013. The Care Centre, Keele University, Keele and 4Division of Epidemiology sample size was 21. The three programmes varied in size, with 4 in the and Public Health, University of Nottingham, Nottingham, UK first, 5 in the second and 12 in the third. FAME consists of a 6-week 2 h educational group session. The first hour consists of an educational Background: SLE is a complex multisystem disease which can be component and the second hour focuses on goal setting. Educational difficult to diagnose early. Studies have found long delays between topics include, fatigue, energy conservation, exercise, stress, pain first symptom and SLE diagnosis, but it is not clear why these delays management, joint protection and nutrition. A mixed methods design occur. It could be that people with SLE are not presenting to primary was used comprising of a quasi-experimental design. Quantitative care, presenting with non-specific symptoms, or being diagnosed with data were collected using outcome measures administered immedi- alternative rheumatic diseases. If SLE diagnosis could be made earlier ately before intervention (T1), immediately post (T2) and 8 weeks post outcomes may be improved. Our aims were to examine consultation intervention (T3). Qualitative data were collected through focus groups rates, presenting symptoms and previous diagnoses in primary care in and individual interviews. Non-parametric statistics were used to the 5 years preceding SLE diagnosis compared with controls; and to analyse the differences based on group size and number of sessions produce a risk prediction model to predict earlier SLE diagnosis. attended. Thematic analysis was carried out on the qualitative data Methods: A case–control study was conducted using the UK Clinical Results: Group size appeared to impact on results. Statistically Practice Research Datalink, an anonymized database of general significant improvements were seen in the largest group only (n ¼ 12) in practice records for approximately 12 million people. Incident SLE Fatigue Severity Scale (FSS) scores betweenT1 and T3 (P ¼ 0.035) and cases diagnosed between 1999 and 2012 were practice-matched to LupusQol subscales of physical health (P ¼ 0.008) between T1 and T2 four controls. Participants were randomly separated by practice to a and of fatigue between T1 and T3 (P ¼ 0.043). No significant changes development (two-thirds) or validation dataset (one-third). Univariate were seen in the smaller groups. Group attendance appeared to odds ratios were calculated for age, gender, consultation rate, impact the results. A statistically significant improvement was seen in selected presenting symptoms and previous diagnoses in the 5 the FSS between T1 and T2 for participants that attended four or less years preceding SLE diagnosis. Backward stepwise logistic regression sessions (P ¼ 0.046). For participants that attended five or more was used to develop a risk prediction model from selected variables. sessions statistically significant improvements were seen in anxiety Model discrimination was tested using receiver-operating character- betweenT2 and T3 (P ¼ 0.023), depression between T1 and T3 istic (ROC) curves. (P ¼ 0.005), self-efficacy between T1 and T2 (P ¼ 0.046) and in the Results: In the 5 years preceding diagnosis, people with SLE had a LupusQol subscales burden to others between T1 and T3 (P ¼ 0.023) significantly higher consultation rate compared with controls (median and fatigue between T1 and T2 (P ¼ 0.036) and T1 and T3 (P ¼ 0.008). 9.2 vs 3.8 consultations per year). They were significantly more likely to Thematic analysis revealed an improved sense of acceptance and be female and present with symptoms suggestive of SLE (Table 1). reduction of guilt in relation to SLE and fatigue. An increase in They were also more likely to have been previously diagnosed with confidence in communicating with health professionals was described. another rheumatic disease (Table 1). A risk prediction model was Conclusion: An occupational therapy educational behavioural group developed using age, gender, eight symptoms and consultation rate, programme may facilitate an improved ability to manage fatigue and which had good discrimination in both the development (ROC 0.8528) participation in activities. Group size appeared to show more positive and validation datasets (ROC 0.8489). i166 Thursday 30 April 2015 POSTER VIEWING III

Conclusion: In the 5 years prior to diagnosis, people with SLE consult were given an index date the same as the diagnosis date of the their general practitioner more frequently and with symptoms matched case. The incidence of CVD, stroke, ESRF, cancer, attributable to SLE. This confirms that there are potential opportunities osteoporosis and infection were calculated per 1000 person-years for earlier diagnosis. A risk prediction model has been developed and stratified by age and gender. Incidence rate ratios (IRR) were used which may assist this in clinical practice but which requires external to compare cases with controls. A global measure of comorbidity, the validation before use. Charlson Index, was calculated for cases and controls at baseline and Disclosure statement: M.D. has received personal fees from ad hoc 10 years following diagnosis or matched index date. Charlson Index advisory boards for gout and OA for AstraZeneca, Menarini, Nordic was categorized into four groups and compared using the chi-squared Biosciences, Novartis and Pfizer, outside the submitted work. P.L. has test for trend. served on speakers’ bureaus on behalf of Pfizer (unconnected to SLE); Results: Comparing the 7732 prevalent cases of SLE with matched and has served on an advisory board for Eli Lilly. G.D. has received controls the IRR for CVD was 2.49 (95% CI 2.14, 2.89), stroke 2.27 personal fees from advisory boards and presentations at meetings (95% CI 1.88, 2.73), ESRF 10.96 (95% CI 6.64, 18.07), cancer 1.57 from MSD, Pfizer, Lilly, Menarini, Servier, Prostrakan, Amgen, GSK and (95% CI 1.44, 1.72), osteoporosis 3.07 (95% CI 2.76, 3.42) and Consilient. W.Z. has received honoraria from Savient for Pegloticase infection 1.87 (95% CI 1.77, 1.97). All were significantly higher in and from Daiichi Sankyo for topical loxoprofen patches. All other people with SLE (P < 0.001). Men with SLE had higher rates of CVD, authors have declared no conflicts of interest. stroke and cancer than women with SLE, whereas women had higher rates of infection and osteoporosis. Except for infection, those at 298 TABLE 1. Univariate analysis younger ages had the greatest risk of comorbidity compared with Variable Cases, % Controls, % Univariate P-value controls. Both at diagnosis and 10 years cases had a significantly (n ¼ 1739) (n ¼ 6952) odds ratio higher Charlson Index than controls (P for trend <0.001). (95% CI) Conclusion: People with SLE have a greater burden of comorbidity Gender 1465 (84.2) 3515 (50.5) 5.23 (4.56, 6.00) <0.001 than people without SLE both before and after diagnosis. People with Symptom SLE are more likely to develop CVD, stroke, ESRF, cancer, Arthritis or arthralgia 622 (36) 727 (10) 4.77 (4.21, 5.40) <0.001 osteoporosis and infection than people without SLE. This increased Rash 744 (43) 685 (10) 6.84 (6.05, 7.74) <0.001 risk is apparent at all ages, but is highest in young people. Fatigue 291 (17) 472 (7) 2.76 (2.36, 3.23) <0.001 Disclosure statement: M.D. has received personal fees from ad hoc Alopecia 66 (4) 57 (1) 4.77 (3.33, 6.83) <0.001 advisory boards for gout and OA for AstraZeneca, Menarini, Nordic Sicca 102 (6) 86 (1) 4.97 (3.72, 6.66) <0.001 RP 77 (4) 21 (0) 15.29 (9.41, 24.85) <0.001 Biosciences, Novartis and Pfizer, outside the submitted work. P.L. has Serositis 72 (4) 59 (1) 5.05 (3.56, 7.15) <0.001 served on speakers’ bureaus on behalf of Pfizer; and has served on Non-specific symptoms 156 (9) 149 (2) 4.50 (3.57, 5.67) <0.001 advisory board for Eli Lilly. G.D. has received personal fees from Nephrotic syndrome 8 (0) 1 (0) 32.12 (4.02, 257.01) <0.001 advisory boards and presentations at meetings from MSD, Pfizer, Lilly, Peripheral oedema 151 (9) 323 (5) 1.95 (1.60, 2.39) <0.001 Menarini, Servier, Prostrakan, Amgen, GSK and Consilient. W.Z. has Proteinuria 13 (1) 32 (0) 1.63 (0.85, 3.11) 0.14 received honoraria from Savient for Pegloticase and from Daiichi Thrombosis 58 (3) 50 (1) 4.76 (3.25, 6.98) <0.001 Sankyo for topical loxoprofen patches. All other authors have declared Fever 51 (3) 62 (1) 3.36 (2.31, 4.88) <0.001 Lymphadenopathy 54 (3) 74 (1) 2.98 (2.09, 4.25) <0.001 no conflicts of interest. Abnormal weight loss 21 (1) 26 (0) 3.26 (1.83, 5.80) <0.001 Mouth ulcers 58 (3) 64 (1) 3.71 (2.59, 5.32) <0.001 Headache 296 (17) 648 (9) 2.00 (1.72, 2.32) <0.001 300. LUPUS MYOCARDITIS: CLINICAL, SEROLOGICAL, AND Depression 348 (20) 784 (11) 1.97 (1.71, 2.26) <0.001 IMAGING PREDICTORS OF TREATMENT RESPONSE Seizure 13 (1) 20 (0) 2.61 (1.30, 5.26) 0.01 1 1 1 Psychosis 2 (0) 9 (0) 0.89 (0.19, 4.11) 0.88 Shirish R. Sangle , Leena J. Yalakki , Kaushik Sanyal , 1 1 1 Confusion 10 (1) 27 (0) 1.48 (0.72, 3.07) 0.29 Hanna Blakey , Sethu Mani-Babu , Andrew Rutherford , Miscarriage 1 (0) 1 (0) 4.00 (0.25, 63.97) 0.33 Valentina Puntmann2, Gerry Carr-White3 and David P. D’Cruz1 Anaemia 151 (9) 190 (3) 3.38 (2.71, 4.22) <0.001 1Louise Coote Lupus Unit, 2Cardiovascular Imaging and 3Cardiology, Thrombocytopenia 15 (1) 5 (0) 12.09 (4.39, 33.31) <0.001 Guy’s and St Thomas’ NHS Foundation Trust, London, UK Lymphopenia 2 (0) 0 (0) Myalgia or myositis 0 (0) 0 (0) Transverse myelitis 0 (0) 0 (0) Background: To describe the clinical, serological and radiological Previous diagnosis features of myocarditis in SLE. Chronic fatigue 19 (1) 12 (0) 6.39 (3.10, 13.19) <0.001 Methods: We retrospectively analysed 19 patients with SLE and APS syndrome with a clinical diagnosis of myocarditis based on clinical, serological FM 33 (2) 17 (0) 7.89 (4.39, 14.20) <0.001 and imaging studies. All patients fulfilled ACR classification criteria for RA 80 (5) 31 (0) 10.77 (7.09, 16.35) <0.001 lupus and Sydney consensus criteria for APS. There were 17 patients Other CTD 112 (6) 22 (0) 21.68 (13.69, 34.36) <0.001 Epstein–Barr virus 2 (0) 6 (0) 1.33 (0.27, 6.61) 0.73 with SLE, 2 with SLE and RA overlap and 2 with APS (1 with SLE). The data collected included disease duration, organ involvement, serolo- gical markers, troponin, NT-proBNP levels and cardiac imaging. Results: There were eight Caucasians, six Asians and five Afro- 299. THE BURDEN OF COMORBIDITY IN SYSTEMIC LUPUS Caribbean patients. The median age was 42 (25–66) years; 16 were ERYTHEMATOSUS female and 2 were male. The median SLE duration was 8.5 years (4–24). Cutaneous involvement was seen in 14 patients (68%), arthritis 1,2 1 3 Frances Rees , Michael Doherty , Matthew Grainge , in 14 (68%), renal involvement in 13 (63%), haematological abnorm- 1,2 4 1 Peter Lanyon , Graham Davenport and Weiya Zhang alities in 9 (43%), neurological involvement in 6 (28%) and pulmonary 1 Division of Rheumatology, Orthopaedics and Dermatology, involvement in 1. Seventeen were positive for ANAs, 15 anti-dsDNA University of Nottingham, 2Rheumatology, Nottingham University antibodies, 2 RF and anti-CCP antibodies. Eight were positive for anti- Hospitals NHS Trust, 3Division of Epidemiology and Public Health, Ro antibodies, eight had anti-RNP antibodies and seven had anti-Sm University of Nottingham, Nottingham and 4Arthritis Research UK antibodies. Antiphospholipid antibodies were present in eight patients Primary Care Centre, Keele University, Keele, UK and two had APS with previous thrombosis. Low C3 and C4 were observed in 12 and 10 patients, respectively. Median troponin levels in Background: SLE, a chronic autoimmune disease, is associated with 16 patients were 92 (2–694) ng/l. Twelve (55 %) had abnormal significant comorbidity which can impair quality of life. The risk of echocardiography with median EF of 36% (31–65%), seven had left cardiovascular disease (CVD) and stroke for people with SLE is ventricular dysfunction, two had global systolic dysfunction, two had recognized, but some studies only found an increased risk in young ventricular dyskinesia, three had left ventricular hypertrophy and two people. The risk of malignancy in people with SLE is controversial. The had biatrial dilatation. Six out of seven (35 %) patients had abnormal incidence of osteoporosis and end-stage renal failure (ESRF) in people MRI scans. Four had left ventricular dysfunction, two had transmural with SLE in the UK is unknown. Infection is a major cause of morbidity scars and one had myocarditis with pericardial effusion. Cardiac failure in SLE, but analysis from a community perspective has not been was seen in five patients (25%). Median NT-proBNP levels in seven undertaken. We aimed to estimate current comorbidity in people with patients was 3750 (17–70 000) ng/l. Four patients had pericardial SLE in the UK for the period 1999–2012, with particular reference to effusions. Fifteen (70%) patients had three or more organs involved CVD, stroke, ESRF, cancer, osteoporosis and infection. based on British Isles Lupus Assessment Group scores of B and A. Methods: A retrospective cohort study was conducted using the Thirteen (60%) patients had three or more serological markers. Five Clinical Practice Research Datalink (CPRD), a longitudinal database of patients received CYC and seven received MMF as remission- general practice records deemed to be representative of the UK inducing therapy; one required IVIGs. Nine patients were maintained population. Between 1999 and 2012, prevalent cases of SLE were on MMF, AZA and MTX along with corticosteroids. Two patients identified and matched by age, sex and practice to four controls who received rituximab. Twelve patients received ACE inhibitors, 11 POSTER VIEWING III Thursday 30 April 2015 i167

received b-blockers, three received diuretics and two were on Background: To determine the length of stay, cost of hospitalization anticoagulation. Two patients died, one having failed all therapies and discharge disposition among patients hospitalized with ischaemic including rituximab. All others had good recovery. stroke with SLE in comparison with the general ischaemic stroke Conclusion: Lupus myocarditis may be more prevalent in patients population. with multi-organ involvement. Patients with triple or more serology Methods: We queried the Healthcare Cost and Utilization Project’s markers and low complement levels may be at high risk of lupus (HCUP) Nationwide Inpatient Sample (NIS) between 2004 and 2010 myocarditis. Response to immunosuppressive therapy is encouraging. and separated the hospitalizations due to or with ischaemic stroke Disclosure statement: The authors have declared no conflicts of interest. using International Classification of Diseases 9 diagnostic codes previously established by HCUP. Among this population, we identified the patients with SLE and calculated the average length of stay and 301. HYPERHOMOCYSTEINAEMIA IN PATIENTS WITH cost of hospitalization and compared it to the general ischaemic stroke ANTIPHOSPHOLIPID SYNDROME: ITS RELATIONSHIP WITH population. In addition, we also compared the discharge disposition THE STATE OF CARDIOVASCULAR SYSTEM among these populations. Using SAS version 9.2, survey procedures Sergii Shevchuk1, Inna Kuvikova1, Iuliia Segeda1 and were used to identify univariate predictors of ischaemic stroke. Olena Galiutina1 Results: A total of 790 912 (weighted n ¼ 3 900 707) patients who were 1Rheumatology, Institute of Invalid Rehabilitation, Vinnitsya, Ukraine hospitalized with ischaemic stroke were available for analysis, of which 3428 (weighted n ¼ 16 828) had SLE. On univariate analysis, the Background: The appearance, formation and progression of cardio- average length of stay for SLE patients was 8.4 0.17 compared with vascular pathology are not always associated with the presence of 7.0 0.01 in the general population (P < 0.0001). The average cost of well-known traditional risk factors. States such as myocardial hospitalization among patients with SLE was 62 029 1775 US dollars infarction, stroke, peripheral vascular lesions may occur in the compared with 45 510 85 US dollars for the general population absence of well-known genetic and environmental risk factors, (P < 0.0001). In the general population, 44.8% of the patients were indicating the necessity of finding another factor able to cause discharged home and 46.1% were discharged to a facility (data cardiovascular diseases. Hyperhomocysteinaemia (HHcy) may be missing for 9% of the population); in patients with SLE, 52.4% were among these factors because it is involved in remodelling of the discharged home and 38.7% were discharged to a facility (data heart and thrombosis. The frequency of HHcy in patients with APS is missing for 8.9% of the population; P < 0.0001). not clear. It is still unexplored the role of HHcy in formation of Conclusion: There are significant discrepancies in the length of endothelium dysfunction in patients with APS. The aim of the study hospitalization, cost of hospitalization and the discharge disposition was to examine the frequency of HHcy in patients with different types among SLE population hospitalized with ischaemic stroke compared of APS and to evaluate its place in the formation of endothelium with the general population. The increased cost of hospitalization may dysfunction and atherosclerotic vascular lesions. be related to the increased length of stay and the increased amount of Methods: The study involved 82 patients: 34 (41.6%) patients with diagnostic workup SLE patients might be getting in the hospitals. primary APS (PAPS) and 48 (58.4%) with secondary APS (SAPS). The Fewer patients with SLE are discharged to a facility, which could be control group comprised 37 healthy individuals. The total homocys- related to lower morbidity of ischaemic strokes due to SLE. This could teine (Hcy) level, soluble thrombomodulin (sCD141) and endothelin-1 be explained by the vasculitic component of SLE, which tends to level were determined by ELISA. The carotid intima-media thickness cause smaller infarction with better prognosis. (IMT) was evaluated in all patients. Disclosure statement: The authors have declared no conflicts of interest. Results: In patients with APS average Hcy level was significantly higher at 52.5 (95% CI 8.61, 25.0 mmol/l) than in the control group. The 303. PREDICTORS OF BONE LOSS OVER TIME IN PATIENTS frequency of optimal Hcy level (less than 10 mmol/l) was 5.2 times WHO HAVE SYSTEMIC LUPUS ERYTHEMATOUS lower, and the frequency of patients with extremely high (10–15 mmol/ Richa Sinha1 and Marwan Bukhari1 l) and high Hcy (above 15 mmol/l) 3.0 and 4.1 times higher than in the 1 control group. The average Hcy level was higher by 13.7% in patients Rheumatology, Royal Lancaster Infirmary, Lancaster, UK with SAPS compared with those with PAPS. The development of HHcy in patients with APS was associated with a significant increase in Background: Research shows that BMD over time occurs in patients endothelial dysfunction. In patients with HHcy, thrombomodulin and with SLE who were taking steroids. No study has shown bone density endothelin-1 levels were significantly higher (1.6 and 2.2 times) than in loss over time independent of steroids. The aim of this observational patients with optimal Hcy levels. Also, the study has shown the study was to investigate predictors of bone loss over time in the presence of a significant association between the level of thrombo- lumbar spine and femoral neck in patients who have SLE. modulin and enlotelinu-1 (r ¼ 0.45, 0.44 and r ¼ 0.38, 0.33, respec- Methods: Data from male and female patients who had SLE attending for tively) with serum Hcy level. HHcy formation in patients with APS was more than one DXA assessment between 2004 and 2014 in the North also associated with a significant increase of IMT. West of England were used. The rate of bone loss over time was Conclusion: Thus the high frequency of HHcy and its close relation- calculated in change in BMD per year for both the spine and femoral neck. ship with cardiovascular injury can be seen as an important risk factor Univariate and a stepwise multivariate regression was fitted including age, of cardiovascular disease in patients with APS. BMI, first BMD, steroid therapy, smoking, and excess alcohol history. Disclosure statement: The authors have declared no conflicts of interest. Results: 83 patients were included in the study. The mean age of patients was 47.21 (interquartile range 41.00–54.48). 95% of the patients were female. The mean bone loss rate in the lumbar spine was 0.004 g/cm2/ year. In the univariate and multivariate analysis looking at bone loss rate in 302. DIFFERENCE IN LENGTH AND COST OF the lumbar spine, first BMD and smoking were found to be statistically HOSPITALIZATION AND DISCHARGE DISPOSITION AMONG significant and therefore had a role in predicting bone loss. In the femoral SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS neck, smoking was the only significant predictor of bone loss. Table 1 HOSPITALIZED WITH ISCHAEMIC STROKE COMPARED WITH shows the coefficients for both the univariate and multivariate analyses THE GENERAL POPULATION: A NATIONWIDE ANALYSIS done on lumbar spine (L1–L4) and femoral neck (left). Khushboo Sheth1, Tapan Mehta2, Vishad Sheth3, Ronak Soni4, Conclusion: In conclusion, the common predictor of bone loss over Kathan Mehta5 and Christopher Scola6 time in patients with SLE was smoking. All other variables were found 1Internal Medicine, 2Neurology, University of Connecticut, Hartford, to be insignificant in the multivariate analysis including steroid therapy. CT, 3Internal Medicine, Mercy Catholic Medical Center, Yeadon, PA, This has not previously been reported on and further research is USA, 4Internal Medicine, Government Medical College, Surat, India, needed to investigate this. 5Internal Medicine, University of Pittsburgh, Pittsburgh, PA and Disclosure statement: The authors have declared no conflicts of 6Department of Rheumatology, Hartford Hospital, Hartford, CT, USA interest.

303 TABLE 1. The coefficients for univariate and multivariate analyses looking at predictors of bone loss in SLE Predictor Univariate coefficient Multivariate coefficient Univariate coefficient Multivariate coefficient (lumbar spine) (lumbar spine) (femoral neck) (femoral neck) Smoker 0.0096 (P ¼ 0.02) 0.0086 (P ¼ 0.04) 0.0070 (P ¼ 0.01) 0.0070 (P ¼ 0.01) Age 0.0002 (P ¼ 0.30) 0.0001 (P ¼ 0.53) First bone density 0.0283 (P ¼ 0.046) 0.0240 (P ¼ 0.09) 0.0168 (P ¼ 0.11) BMI 0.6099 (P ¼ 0.87) 0.6433 (P ¼ 0.79) Steroid use 0.0079 (P ¼ 0.42) 0.0032 (P ¼ 0.62) Excess alcohol 0.0094 (P ¼ 0.49) 0.0052 (P ¼ 0.56) i168 Thursday 30 April 2015 POSTER VIEWING III

remaining 34 who did not have LVV, 4 received a new diagnosis of malignancy and 2 were diagnosed with atheromatous disease (not VASCULITIS classified as LVV). LVV was demonstrated in 2/7 of the patients with known GCA and in 1/9 of the patients with known PMR. Of the patients with positive scans, four were receiving prednisolone (range 2.5– 40 mg) at the time of the scan, but only two of them were receiving 304. UTILITY OF FLUORO-DEOXY-GLUCOSE POSITRON 10 mg or more. The mean dose of prednisolone was 6 mg in those with EMISSION TOMOGRAPHY IN DIAGNOSING LARGE VESSEL a positive result (LVV) and 12 mg in those with negative scan (no LVV). VASCULITIS: PRELIMINARY DATA FROM A UK CENTRE The cumulative prednisolone dose in the 4 weeks prior to the scan was 160 mg and 201 mg, respectively. CRP: Of the patients with positive Benjamin Clarke1, Ritu Malaiya1, Helen Linklater1 and Sanjeev Patel1 scans, 2 had CRP levels of <10 mg/l. The mean (range) CRP level was 1Rheumatology, Epsom & St Helier NHS Trust, Carshalton, UK 64.1 (<5 to 149) mg/l in those with a positive scan and 36.9 (<5 to 95) in those with a negative scan. Patients with CRP levels <10 mg/l and Background: PET has uncertain utility for the diagnosis of large vessel positive FDG-PET-CT were not receiving high-dose prednisolone. vasculitis (LVV). We reviewed our patient cohort with suspected LVV Conclusion: During the audit period, about 1 in 5 FDG PET-CTs who underwent PET scanning, and examined the data to determine done for non-oncological reasons revealed LVV, and about 1 in 10 whether there were helpful patient characteristics to predict positive revealed an unexpected malignancy. Most, but not all, of the scans. patients for whom PET-CT revealed LVV were receiving <10 mg Methods: All PET requests for suspected LVV over the preceding 12- prednisolone at the time of the scan and had a CRP level of month period were reviewed. Data collected were patient demo- >10 mg/l. None of the cases in which LVV was detected were on graphics, clinical characteristics at presentation, initial working high-dose prednisolone with a CRP level of <10 mg/l. On the basis diagnosis (GCA was categorized as low, moderate or high probability), of our audit, clinicians requesting PET-CT scans should be aware of ESR and CRP (at presentation), steroid dose, temporal artery biopsy the factors associated with detection of LVV. We will re-audit to (TAB), reason for PET request and PET results including maximum determine whether referral patterns (CRP, prednisolone) have standard uptake value (SUVmax). changed as a result of this local learning, and whether this results Results: 15 patients underwent PET scanning. The female:male ratio in more targeted use of scans and a greater likelihood of detecting was 2:1 and the mean age was 67 years (range 48–87 years). The initial LVV when it is clinically suspected. working diagnoses were GCA in 10 patients (probability low in two, Disclosure statement: S.L.M. is a NIHR-funded Clinician Scientist. All moderate in four and high in four) or PMR with LVV in the remaining five other authors have declared no conflicts of interest. patients. The indication for PET was query active LVV in 12/15 patients (80%) and LVV or malignancy in 3/15 patients (20%). Based on the 306. HOW DO GENERAL PRACTITIONERS MANAGE PET findings a final diagnosis of LVV was made in 8/15 (53%) patients. SUSPECTED GIANT CELL ARTERITIS PET uptake was borderline in 1/15 patients and negative in 6/15 patients. Of the six with negative PET scans, three are being Toby Helliwell1, Sara Muller1, Samantha L. Hider1, Jane Richardson1 investigated for incidental findings (thyroid nodule, lung nodule and and Christian Mallen1 sigmoid colon uptake). A negative TAB was reported in 5/8 (63%) 1Primary Care and Health Sciences, Keele University, Keele, UK patients with positive PET scans. TAB was not performed in 2/8 patients with positive PET scans, with a biopsy pending in the final Background: Background: GCA is the commonest large vessel patient. Prednisolone use prior to PET varied, with a mean daily dose vasculitis yet a full time UK general practitioner (GP) can expect to of 14.6 mg (range 0–40 mg). The mean duration of steroid treatment at see just one case, at most every 1–2 years. Untreated GCA can lead to this dose in TAB-negative, PET-positive patients was 4.2 months permanent visual loss, thus it is essential GPs recognize and instigate (range 0–16 months. There was no difference in ESR and CRP appropriate management at an early stage, including urgent referral for between PET-positive and PET-negative patients (Mann–Whitney U specialist review and diagnostic confirmation. Our objective was to testing). SUVmax ranged from <1.0 to 9.5 in the PET-positive group, investigate the management of GCA in UK General Practice and to with a mean value of 4.1. identify barriers to effective treatment. Conclusion: Our preliminary data show that PET has a role in Methods: A postal questionnaire survey of 5000 randomly selected establishing the presence of LVV in biopsy negative cases (PET was UK GPs. Questions included experience of diagnosing and managing positive in 63% of TAB-negative patients). It has been suggested that patients with GCA. Simple descriptive statistics were used for the CS use can reduce the sensitivity of PET for diagnostic purposes, closed response data and thematic analysis was used for open ended however our data suggest that PET scans can be positive even in questions. patients who have had prolonged treatment with steroids. Results: 1249 (25.14%) questionnaires were returned. The mean age Disclosure statement: The authors have declared no conflicts of of responders was 43 years and they had been qualified as a GP for a interest. mean of 14 years (S.D. 9.03). 879 responders (70.4%) indicated that they had managed a patient with GCA. In line with UK guidance, 983 (78.7%) of responders reported that they initiated treatment with 305. FACTORS ASSOCIATED WITH DETECTION OF LARGE between 40 and 60 mg of prednisolone. 244 (20%) responders would VESSEL VASCULITIS ON 18-FLORINE refer patients immediately to hospital without doing any investigations FLURODEOXYGLUCOSE POSITRON EMISSION whereas 201 (16.5%) would only refer if initial investigations were TOMOGRAPHY/COMPUTED TOMOGRAPHY SCANS: A abnormal. Less than half of GPs would initiate glucocorticoid treatment SINGLE-CENTRE AUDIT prior to referral. There were marked reported differences in referral Esme Ferguson1, Kavitha Nadesalingam1, Amjad Mohammed2, pathways with 38.3% (n ¼ 478) referring to rheumatology, 29.3% (366) Andrew Scarsbrook2 and Sarah L. Mackie1 to ophthalmology and 11.5% (n ¼ 144) referring to general medicine. 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, Speciality referral was dependent on clinical presentation. Older University of Leeds and 2Department of Radiology, St James’s patients were often referred to elderly care services while patients University Hospital, Leeds, UK with visual symptoms were referred to ophthalmology (if available) or acute services such as accident emergency or acute medicine. Background: 18-Fluorine fluorodeoxyglucose PET-CT (FDG-PET-CT) Thematic analysis of free text comments highlighted the frustration can be used to diagnose large vessel vasculitis (LVV). However, and difficulties GP have with accessing specialist care with some suppression of inflammation with steroids can result in a negative scan responders having to arrange temporal artery biopsy prior to specialist result. We examined data from our centre to determine how often review. GPs were also concerned about a lack of fast track pathways scans were positive and whether this was associated with predniso- to support this patient group. lone therapy. Conclusion: There are marked differences in the treatment and Methods: Records from our trust, a regional PET-CT centre, identified assessment of patients with GCA in the UK, with conflicting referral consecutive patients undergoing PET-CT scans for non-oncological pathways and difficulties in accessing appropriate services. While the purposes over a 2-year period from 2011 to 2013. Medical notes and majority of GPs responding to this survey use appropriate doses of laboratory results were reviewed to determine CRP and prednisolone glucocorticoids, many would not initiate early treatment, contrary to dose at the time of the scan. Descriptive statistics were employed for current guidance. The development of a national standard for fast these audit data. tracking suspected GCA patients to relevant expertise and further Results: Of 70 PET-CT scans identified, 57 were patients of our trust. clinical education of GPs would be beneficial to improve care and Of these, notes were available for 43; 18/43 were male. The median outcomes for patients with GCA. (range) age was 66 (31–81) years. 9/43 patients had a positive scan Disclosure statement: The authors have declared no conflicts of indicating LVV; 8/9 of these were reported as showing aortitis. Of the interest. POSTER VIEWING III Thursday 30 April 2015 i169

307. PAEDIATRIC TAKAYASU’S ARTERITIS: CLINICAL MPA vs 6/39 (15.4%) in GPA. CV event-free survival at 120 months FEATURES AND SHORT TERM OUTCOME was significantly reduced in MPA vs GPA (P ¼ 0.008) but when 1 1 1 1 comparing patients by ANCA type there was no difference (P ¼ 0.27). Durga P. Misra , Amita Aggarwal , Able Lawrence , Vikas Agarwal Employing the predictive risk model, our cohort data were similar to and Ramnath Misra1 1 the EUVAS data in predicting CV events based on age, hypertension Clinical Immunology, Sanjay Gandhi Postgraduate Institute of and PR3 status when comparing the percentage of patients per risk Medical Sciences, Lucknow, India group (low, moderate or high risk; P ¼ 0.53) and CV events by risk group (P ¼ 0.93). Background: Takayasu’s arteritis (TA) is a common large vessel Conclusion: In contrast to the European data, we found no increase in vasculitis in India. It usually starts in young adults; reports on children CV events in North American patients with AASV relative to the are sparse. background population. We have further validated the previous 5-year Methods: Retrospective data analysis of patients diagnosed with TA cardiovascular risk model, proving its transferability to a US inception over last 13 years with onset before 18 years of age was done. Their cohort to stratify individual CV risk in AASV. MPA was associated with presenting features, activity (by Kerr’s criteria), disease extent [by the significantly more CV events than GPA, but no difference was Disease Extent Index-Takayasu (DEI.Tak)] and angiographic findings observed between MPO- and PR3-positive patients, suggesting that were retrieved from case or clinic files. Treatment received and follow- clinical phenotype is more relevant in identifying at risk patients than up data on disease activity, damage [by the Takayasu Arteritis serological status. Damage Score (TADS)] and drug toxicity were also analysed. Disclosure statement: The authors have declared no conflicts of Wherever repeated angiography data were available, the same were interest. analysed. Values are expressed as median with interquartile range in brackets. Results: There were 29 patients (19 girls) with median age at diagnosis 309. THE ASSOCIATION BETWEEN ANCA ANTIBODIES AND of 14 years (13–16) and a delay to diagnosis of 1 year (0.4–2). Common THYROID DISEASE IS INDEPENDENT OF ANCA-ASSOCIATED presenting symptoms were constitutional (24/29), pulse loss (23/29), VASCULITIS hypertension (22/29) and pulse inequality (16/29). The median number Fiona Pearce1, Richard A. Watts2 and Peter Lanyon1 of PRINTO criteria satisfied at diagnosis was 4 (4–5). Patients had 1Rheumatology, Queen’s Medical Centre, Nottingham and extensive disease at presentation with a median DEI.Tak of 12 (9.5– 2 15). 22/27 had elevated acute phase reactants, and 28/29 were active Rheumatology, Ipswich Hospital NHS trust, Ipswich, UK at presentation. Numano’s type V was the commonest angiographic type (22/29). 23/29 received immunosuppressive drugs and 22/29 Background: Anti-thyroid drugs (e.g. propylthiouracil and carbima- required anti-hypertensive drugs [median number of 2 (2–3) anti- zole) have been causally implicated in the development of ANCA- hypertensives]. Follow-up data were available for 18 patients. At a associated vasculitis (AAV) in case reports and case series. Thyroid median follow up of 2.4 years (1.8–5.7), 2/18 were active, whereas all disease has also been associated with AAV in the absence of drug had sustained damage despite being on immunosuppression. The exposure, with one study reporting thyroid disease in 20% of 158 AAV median TADS was 8 (6.8–9.3), with pulse loss and hypertension being cases, compared with 7% of controls. However, it is not clear whether the commonest damage items. Six needed renal artery stenting to ANCA positivity alone, in the absence of AAV, is also associated with control hypertension. Angiographic assessment at least 2 years apart thyroid disease. This is important to establish due to the potential for in six patients showed progression of disease in five, despite their some symptoms of thyroid disease to mimic those of vasculitis. immunosuppression. Methods: As part of an AAV audit, all patients positive for MPO or PR3 Conclusion: Significant damage accrued on follow up despite ANCA (Orgentec Diagnostika ELISA) between March 2006 and June immunosuppression and control of disease activity. Hypertension 2013 were identified. Documentation of presence or absence of remains the major long-term morbidity. thyroid disease was established from clinic letters (PMH and/or Disclosure statement: The authors have declared no conflicts of medication history) and the hospital’s electronic alert system for interest. thyroid disease. The final diagnosis following ANCA testing was recorded. Fisher’s exact test for 2 2 tables of frequencies was calculated using GraphPad. Results: Among 685 patients positive for MPO or PR3 ANCA, the 308. CARDIOVASCULAR OUTCOMES ARE WORSE IN overall prevalence of thyroid disease was 14.2%, compared with UK MICROSCOPIC POLYANGIITIS COMPARED WITH population estimates of 2–3%. Thyroid disease was significantly more GRANULOMATOSIS WITH POLYANGIITIS: DATA FROM AN prevalent in those with MPO antibodies (22.2%) compared with PR3 INCEPTION COHORT OF PATIENTS WITH ANTI-NEUTROPHIL antibodies (9.6%; P ¼ 0.0017). Among MPO-positive patients, the CYTOPLASM ANTIBODY ASSOCIATED SYSTEMIC prevalence of thyroid disease was significantly higher in those without VASCULITIS AAV (30.2%) compared with those with AAV (12.0%), P ¼ 0.0229. Anna Mistry1, Joanna Robson1, Susan L. Hogan2, Caroline Poulton2, Among PR3-positive patients there was no significant difference in the Yichun Hu2, Ronald Falk2 and Raashid Luqmani1 prevalence of thyroid disease according to whether there was a 1Nuffield Department of Orthopaedics, Rheumatology and diagnosis of AAV or not (P ¼ 0.4037), although the overall prevalence in Musculoskeletal Sciences, University of Oxford, Oxford, UK and this group (9.6%) was still higher than the background population. 2UNC Kidney Centre, University of North Carolina, Chapel Hill, NC, Conclusion: ANCA antibodies (particularly MPO), rather than ANCA USA vasculitis alone, are associated with thyroid disease. There are two potential explanations. ANCA production and AAV might cluster within Background: A significant increase in the cardiovascular mortality five the spectrum of autoimmune conditions associated with thyroid year after a diagnosis of ANCA-associated systemic vasculitis (AASV) disease. If so, this association appears stronger than in the diseases has been reported by the European Vasculitis Study Group (EUVAS). more usually associated e.g. RA and SLE, where the prevalence of This association has yet to be established in a non-European cohort. A thyroid disease is estimated at 9.8% and 6.1%, respectively. 5-year predictive risk model was developed from the EUVAS dataset Alternatively, ANCA could be a risk factor for the development of to stratify patients into high, moderate or low risk of a future thyroid disease. This association is also clinically important, as it cardiovascular (CV) event. We describe the CV events occurring in a provides an alternative explanation for MPO/PR3 ANCA in people North American inception cohort with AASV and further validate the without clinical evidence of vasculitis, particularly as some of the existing cardiovascular predictive risk model in this population. symptoms of thyroid disease (e.g. fever, weight loss) can mimic those Methods: A retrospective analysis was performed on 387 patients of vasculitis. Further work is needed to assess whether the presence of recruited to the Glomerular Disease Collaborative Network (GDCN) thyroid disease in MPO/PR3-positive individuals affects their future registry with a new diagnosis of AASV between 1985 and 2007. We risk of developing AAV, and on the mechanism of the association. compared the incidence of CV events following a diagnosis of Disclosure statement: P.L. has served on an advisory board for Eli granulomatosis with polyangiitis (GPA) or microscopic polyangiitis Lilly; is a member of speakers’ bureau on behalf of Pfizer; and has (MPA) to the predicted general population matched for age and received lecture fees from Pfizer. All other authors have declared no gender. Patients were also stratified according to proteinase-3 (PR3) conflicts of interest. or MPO ANCA positivity. We used data from patients without pre- existing CV events to validate the 5-year predictive cardiovascular risk 310. POOR POSITIVE PREDICTIVE VALUE OF PR3 AND MPO model and compared the results with the EUVAS dataset. ANTIBODIES IN DIAGNOSIS OF AAV Results: 39/387 patients (10.1%) experienced at least one CV event during follow up (0.02–27.8 years, median 3.6 years). Although no Fiona Pearce1, Peter Lanyon1 and Richard A. Watts2 significant difference in CV events was observed between our cohort 1Rheumatology, Queen’s Medical Centre, Nottingham and and the background population, 33/39 events (84.6%) occurred in 2Rheumatology, Ipswich Hospital NHS trust, Ipswich, UK i170 Thursday 30 April 2015 POSTER VIEWING III

in group 3 compared with group 1 (137.0 99.0 vs 52.6 54.1, Background: Patients positive for MPO or PR3 ANCA are referred to P < 0.01 and 0.88 0.19 vs 0.68 0.13, respectively; P < 0.05). There rheumatologists. Previous studies have looked at the utility of IIF in the was also a significant difference in a-SMA between group 3 and group assessment of unwell patients. As part of an ANCA-associated 2 (137.0 99.0 vs 90.4 114; P < 0.05). There were no differences in vasculitis (AAV) audit we assessed the role of PR3 and MPO ELISA levels of elastin and ET-1 between these groups. in the routine assessment of patients with possible multisystem Conclusion: There are significant differences in levels of elastin disease. between patients with active PAN and patients with active AAV or Methods: Screening for ANCA was by IIF, positive samples were healthy controls. Elevated serum levels of a-SMA are associated with tested for PR3 and MPO by ELISA (Orgentec Diagnostika), with normal increasing disease activity for SV, especially AAV. upper limits for PR3 of <5 and for MPO of <5. Medical records of all Disclosure statement: The authors have declared no conflicts of patients positive for MPO or PR3 ANCA at a single centre from March interest. 2006 to June 2013 were recorded and the final diagnosis recorded. Results: ANCA testing was positive by IIF in 4685 patients; 687 311 TABLE 1. Biomarkers levels at baseline in patients with active SV and healthy patients were MPO positive or PR3 ANCA positive. 236 (34.4%) had controls new or established AAV, and 451 (65.6%) had conditions other than AAV. Inflammatory bowel disease (IBD) was most common (99 Data Healthy controls, PAN, mean AAV, mean patients 22.0%). Other non-AAV diagnoses included thyroid disease mean (S.D.) (n ¼ 26) (S.D.) (n ¼ 8) (S.D.) (n ¼ 28) (57), infection (18, including TB, HCV, HIV, bacterial leishmaniasis), Elastin, ng/ml 4.82 (2.38) 7.56 (4.04)* 4.00 (2.93)** malignancy (10), uveitis (8), SLE/LN (7), sarcoid (3), cytopenia (4), ET-1, ng/ml 0.27 (0.10) 0.31 (0.11) 0.31 (0.26) BAFF, pmol/l 0.82 (0.22) 0.75 (0.11) 0.82 (0.32) demyelination (4), SSc (2), relapsing polychondritis (2), cocaine abuse a-SMA, ng/ml 44.7 (25.7) 42.3 (58.1) 102.1 (103.1)* (2), Addison’s disease (1) and RA (3). No specific diagnosis was made for the remainder. The sensitivity of MPO/PR3 for AAV was 95.9% and *P < 0.05 compared with the control group, **P < 0.01 compared with PAN. AAV: the specificity was 90.2%; however, the positive predictive value was ANCA-associated vasculitis; BAFF: B-cell activating factor. only 34.4%, whereas the negative predictive value was 99.8%. An increasing titre of MPO or PR3 antibodies was associated with an increased proportion of patients with AAV; however, there was no 312. DEVELOPMENT OF AUTOMATED CLINICAL VIGNETTES threshold above which AAV was universal. Five (10.7%) patients with FOR BIRMINGHAM VASCULITIS ACTIVITY SCORE TRAINING PR3 levels >100 and five (12.2%) patients with MPO100 did not have USING DATA FROM DIAGNOSTIC AND CLASSIFICATION a diagnosis of AAV after careful assessment by a rheumatologist and/ CRITERIA IN VASCULITIS STUDY or nephrologist. IIF was helpful in differentiating AAV, IBD and other 1,2 2,3 2,4 diagnoses. IIF results were reviewed for 80% of patients. In AAV, all Hannah Querin , Jan Sznajd , Benjamin Seeliger , Lorraine O’Neill2,5, Cristina Ponte2,6, Jennifer O’Donoghue2, MPO patients had p-ANCA, and among PR3 patients all had c-ANCA 2,7 8 8 except two who were IIF negative. In those with IBD, 71 (71.7%) had p- Ana F. Rodrigues , Kulveer Mankia , Jessica Gunn , Katarzyna Wawrzycka-Adamczyk3, Joe Rosa2, Joel David8 and ANCA with PR3, 20 (20.2%) had c-ANCA with PR3 and 8 (8.1%) had 2,8 MPO. In other non-AAV patients, PR3 patients were equally likely to Raashid A. Luqmani 1School of Medicine and Dentistry, James Cook University, Cairns, have c-ANCA as p-ANCA, more than 90% of MPO patients had p- 2 ANCA and a few patients had atypical ANCA. Australia, Nuffield Department of Orthopaedics, Rheumatology and Conclusion: The majority of individuals positive for PR3 or MPO ANCA Musculoskeletal Sciences, Oxford University, Oxford, UK, 3 do not have AAV. The most common alternative diagnosis to AAV is Department of Internal Medicine, Jagiellonian University, Krakow, 4 IBD, but vasculitis, infection and malignancy are common. Although Poland, Department of Internal Medicine, Jena University, Jena, 5 the likelihood of AAV appears to increase with higher ELISA titres, Germany, Department of Rheumatology, St Vincent’s University clinicians need to be constantly vigilant in diagnosis as positivity for Hospital, Dublin, Ireland, 6Department of Rheumatology, PR3/MPO has a poor positive predictive value for AAV. The 7Department of Internal Medicine, Centro Hospitalar do Oeste, occurrence of non-classical combinations of IIF and ELISA should Caldas da Rainha, Portugal and 8Department of Rheumatology, alert the clinician that the diagnosis might not be AAV. Nuffield Orthopaedic Centre, Oxford University Hospitals, Oxford, UK Disclosure statement: P.L. has served on an advisory board Eli Lilly; is a member of speakers’ bureau; has received lecture fees from Background: The BVAS is an established evaluation tool for patients Pfizer. All other authors have declared no conflicts of interest. with systemic vasculitis in clinical trials and increasingly in clinical practice, but its use requires training. Recently we have developed and tested an online training system based on a relatively small number of 311. POTENTIAL BIOMARKERS OF POLYARTERITIS cases. Our objective was to create a large pool of representative NODOSA AND ANCA-ASSOCIATED VASCULITIS training clinical vignettes for certification of proficiency in vasculitis assessment using real patient data derived from the Diagnostic and Liubov Petelytska1, Oleg Iaremenko1, Kateryna Iaremenko1 and Classification Criteria in Vasculitis Study (DCVAS). Ganna Mykytenko1 Methods: We extracted clinical items from the DCVAS case record 1Rheumatology, National Medical University, Kyiv, Ukraine form which could directly populate BVAS scoring and allow sub- sequent creation of clinical vignettes. As BVAS was not formally Background: Systemic vasculitis (SV) represents a highly hetero- scored in DCVAS, we created rules to automate BVAS scoring from geneous group of clinicopathological entities. The purpose of this these variables. We developed a language tree for the identified study is to determine new biomarkers that may be used to assess the variables to provide a variety of different terms coding to the same severity of SV and to distinguish PAN from other ANCA-associated stem item in order that the terms could be randomly inserted into a vasculides (AAVs). clinical vignette that would allow clinicians to score BVAS; multiple Methods: Four serum proteins [alpha actin 2 (a-SMA), endothelin-1 phrases for each clinical item allowed us to enrich the diversity of the (ET-1), B-cell activating factor (BAFF) and elastin] were measured in 37 vignettes. We categorized the cases with respect to type of vasculitis patients with AAV (granulomatosis with polyangiitis, 22; eosinophilic and level of difficulty defined by extent and severity of the disease and granulomatosis with polyangiitis, 9; microscopic polyangiitis, 6), 11 confounder conditions. patients with PAN and 26 healthy controls. Among the patients with Results: We created 2116 vignettes for BVAS assessment. We AAV, 24 were positive for c-ANCA and 11 for p-ANCA. At baseline, 9 selected 20 of them by purposive sampling and these were scored patients were without treatment, 26 patients were receiving gluco- by 10 independent clinicians (previously certified in clinical assess- corticoids and 13 patients were receiving some immunosuppressants ment of vasculitis) to test their validity. Individual scores were and glucocorticoids. Clinical activities of patients were calculated compared against the gold standard defined by the automated according to the BVAS. All patients were divided into three groups BVAS validated by an expert panel reviewing the original data. In the according to their BVAS: group 1, BVAS 0–11 (n ¼ 12); group 2, BVAS preliminary validation, mean percentage of agreement with the 12–23 (n ¼ 23); and group 3, BVAS 24–35 (n ¼ 13). reference standard per case was 93.7% (85.6–97.8) with a mean Results: There were significant differences in levels of elastin time to completion of 2.5 (1.8–5.4) min. We identified some systematic (increased approximately twofold) between PAN and AAV groups in errors of item attribution which enabled us to improve the language patients with active SV (BVAS >11) or healthy controls. Mean levels of tree. Pass mark and time to completion appeared to correlate with the ET-1 and BAFF were similar between these groups (Table 1). a-SMA level of difficulty of the cases and was comparable to the non- levels were significant higher in patients with AAV compared with automated case scenarios from the current training package. healthy controls, and higher than in PAN patients, but the latter Conclusion: We successfully applied a new methodology to auto- difference did not reach statistical significance. Estimating biomarkers matically generate clinical vignettes from real patient data. In addition, levels in groups of patients with different clinical activity (determined we extracted the BVAS from the DCVAS data and used it in validation by BVAS) showed a significant increase in levels of a-SMA and BAFF of the clinical vignettes, which proved to be applicable for the purpose POSTER VIEWING III Thursday 30 April 2015 i171

of training in BVAS assessment. The larger set of vignettes will allow us Cerebrovascular and cardiovascular diseases are thought to to select cases for evaluation at random, providing a better training be increased in patients with GCA but risk factors or indicators opportunity for clinicians. Automated vignette generation could be for this are not confirmed. It has previously been suggested applied to other study databases and provide a novel tool to create that social deprivation is associated with visual ischaemic data-driven training scenarios. complications in patients with GCA. This study evaluated the risk of Disclosure statement: R.A.L. has received consulting fees from GSK, cerebrovascular and cardiovascular disease in patients with GCA Nordic and ChemoCentryx; and has received lecturing fees from compared with matched controls, and identified predictors of these Roche, Nippon Kayaku. All other authors have declared no conflicts of outcomes. interest. Methods: A UK General Practice Research Database from 1991 to 2010 was used for a parallel cohort study of 5827 patients with GCA and 37 090 controls, matched on age, gender and location (GP 313. WHY LEG ULCERS DO NOT HEAL? HIGH PROPORTION practice). A multivariable competing risk model (with noncardiovas- OF SMALL VESSEL VASCULITIS IN A PROSPECTIVE STUDY cular-related death as the competing risk) determined the relative risk FROM KERALA, INDIA (subhazard ratio, SHR) between non-GCA and GCA patients for each Vinod Ravindran1, Sunil Rajendran2 and Ranjish Vijayan2 of the following outcomes: cardiovascular disease; cerebrovascular 1Department of Rheumatology, National Hospital and 2Department of disease; and cardiovascular or cerebrovascular disease (three , PVS Hospital, Calicut, India analyses).The model adjusted for smoking history, history of hyperten- sion, prior use of anti-hypertensives, history of diabetes or prior use of Background: Nonhealing cutaneous ulcers of lower limbs can have diabetic medications, history of hyperlipidaemia, prior use of lipid- several different aetiologies. It is likely that the patients with such lowering medications and Index of Multiple Deprivation (IMD) quintiles. ulcers would be treated with empirical therapies and may also undergo The model was then run on each cohort separately to identify (unnecessary) venous procedures. Small vessel vasculitides (leucocy- predictors of cerebrovascular and cardiovascular disease (age and toclastic or non-leucocytoclastic) are one of the important causes of gender were now included). non-healing cutaneous leg ulcers. The primary objective of this Results: When comparing the GCA cohort with the non-GCA cohort, prospective study was to ascertain the cause of non-healing the SHR (95% CI) for cerebrovascular disease [1.45 (1.31, 1.60)], cutaneous ulcers of the lower limbs. cardiovascular disease [1.49 (1.37–1.62)], and cerebrovascular or Methods: Between May 2010 and April 2013 (3 years) consecutive cardiovascular disease [1.47 (1.37, 1.57)] were increased. In the GCA adult patients (age 18–75 years) who had one or more persistent leg cohort only, predictors of the composite outcome of cardiovascular or ulcers (with or without a history of recurrent ulcerations in legs) for cerebrovascular disease included increasing age [1.98 (1.62, 2.42); more than 2 years presenting to us were prospectively enrolled. P < 0.001] in those aged over 80 years compared with those less than Relevant details were extracted using a predefined proforma and 65 years); male gender [1.20 (1.05, 1.38), P < 0.001] and those in the included: demographic details, drug history, comorbidities, clinical most deprived IMD quintile compared with the least deprived [1.34 features, investigations of markers including ANCA, complement (1.01, 1.78), P < 0.05]. A history of hypertension was predictive of levels, cryoglobulins, HIV and hepatitis viral were done by serology cardiovascular disease within the GCA cohort [1.53 (1.14–2.05), and venous and arterial Doppler, microscopy and culture of the ulcer P < 0.01] but no other significant associations were seen between swab in instances of infected-looking ulcers. Previous biopsies were the other conventional cardiovascular risk factors and either cardio- reviewed and fresh biopsies were obtained from the ulcer edges and vascular or cerebrovascular disease as either separate or composite also from the non-ulcerated sites where suitable skin lesions were also outcomes. present. In cases of ulcers deemed to be a manifestation of a primary Conclusion: Patients with GCA are 50% more likely to have systemic vasculitis based on the European Medicines Agency cerebrovascular disease or cardiovascular disease than age, gender classification, the BVAS was used to assess disease activity. and location matched controls. This effect is independent of Results: A total of 51 patients were assessed. Mean age was 53 10.3 conventional cardiovascular risk factors but may be associated with years and 39 (76%) were male. Eight (16%) patients were diabetic. higher levels of social deprivation. History of some type of venous surgery was present in 30 (59%) and 9 Disclosure statement: J.C.R. has received consulting fees from had such procedures more than once. Biopsy confirmed small vessel GSK. B.D. has received consulting fees from GSK, Roche, Pfizer vasculitis of various types in a majority 39 (76%) patients, chronic and Servier. R.L. has received consulting fees from GSK, Roche, infections were responsible in 4 (8%), whereas in 8 (16%) no single Pfizer and Novartis. All other authors have declared no conflicts of cause could be established. Drug-induced cutaneous vasculitis was not interest. present in this cohort. In nine (18%) patients, the leg ulcers were one of the manifestations of a primary systemic vasculitis: four with granulo- 315. DEVELOPMENT OF AN ANCA-ASSOCIATED matosis with polyangiitis (GPA) (4), two with eosinophilic GPA, two with VASCULITIS PATIENT-REPORTED OUTCOME MEASURE: microscopic polyangiitis and one with PAN. Leg ulcers in these patients IDENTIFICATION OF SALIENT THEMES AND CANDIDATE ran an indolent course with a variety of low to moderate grade of activity QUESTIONNAIRE ITEM DEVELOPMENT features reflected also in the BVAS range of 9–15. All patients with small vessel vasculitis were treated with immunosuppressive therapy including Joanna C. Robson1, Jill Dawson2, Nataliya Milman3, glucocorticoids with good effect [complete healing of ulcer(s) in 21 Katherine Kellom4, Peter Cronholm5, Judy Shea5, patients with no relapse in 24 weeks]. Raashid Luqmani1, Susan Ashdown1, John Farrar5, Conclusion: In this cohort of patients with chronic nonhealing leg Donald Gebhart6, Georgia Lanier7, Carol McAlear5, ulcers, small vessel cutaneous vasculitis emerged as the leading Jacqueline Peck1, Gunnar Tomasson8 and Peter Merkel5 cause and a majority benefited from subsequently instituted specific 1Rheumatology, NDORMs, University of Oxford, 2Nuffield measures of treatment. Department of Population Health, University of Oxford, Oxford, UK, Disclosure statement: The authors have declared no conflicts of 3Rheumatology, University of Ottawa, Ottawa, ON, Canada, 4Mixed interest. Methods Research Laboratory, 5Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 6Rheumatology, 7 314. INCREASED RISK OF CEREBROVASCULAR AND Columbus, Columbus, OH, Rheumatology, Boston Medical Centre, 8 CEREBROVASCULAR DISEASE OUTCOMES IN PATIENTS Boston, MA, USA and Rheumatology, University of Reykjavik, WITH GIANT CELL ARTERITIS INDEPENDENTLY Reykjavik, Iceland ASSOCIATED WITH SOCIAL DEPRIVATION Background: Patients with ANCA-associated vasculitides (AAVs), 1 2 2 1 Joanna C. Robson , Amit Kiran , Andrew Hutchings , Nigel Arden , granulomatosis with polyangiitis, eosinophilic granulomatosis with 3 4 5 6 Bhaskar Dasgupta , William Hamilton , Akan Emin , David Culliford polyangiitis (Churg–Strauss) and microscopic polyangiitis often suffer 1 and Raashid Luqmani from persistent disease activity, disease-associated damage, or 1 Rheumatology, NDORMs, University of Oxford, Oxford, treatment side effects, all of which may impact quality of life. There 2 Department of Health Services Research and Policy, London School is currently no disease-specific patient-reported outcome (PRO) for 3 of Hygiene and Tropical Medicine, London, Rheumatology, AAV. The development of a new PRO involves questionnaire item Southend University Hospital NHS Trust, Southend, 4Primary Care development; item reduction and scale generation; and testing scale Diagnostics, University of Exeter, Exeter, 5Clinical Effectiveness Unit, properties such as reliability, validity and responsiveness. It is essential The Royal College of Surgeons, London and 6Faculty of Medicine, that a PRO is developed in compliance with U.S. Food and Drug University of Southampton, Southampton, UK Administration recommendations in order to legitimize its use in clinical trials and in supporting labelling claims for medications. Following Background: GCA is the most common form of vasculitis in the UK, these principles, a multi-national collaboration of researchers and with an incidence of 2.2 cases per 10 000 person-years. patient-partners has been conducting the first stage of questionnaire i172 Thursday 30 April 2015 POSTER VIEWING III

item development. A collaborative approach involving patients from 316. PREDICTORS OF DELAY IN DIAGNOSIS OF GIANT CELL the UK, USA and Canada was feasible and desirable due to the relative ARTERITIS AND ANTINEUTROPHIL CYTOPLASM ANTIBODY rarity of the disease and the ability to create a tool with content validity ASSOCIATED VASCULITIDES: ANALYSIS OF DATA FROM THE (and cultural/linguistic equivalence) appropriate for use in all three DIAGNOSTIC & CLASSIFICATION CRITERIA IN VASCULITIS countries. STUDY Methods: Exploratory semi-structured patient interviews were per- 1,2 2,3 2,4 formed in Oxford, UK, Philadelphia, USA, and Ottawa, Canada. The aim Benjamin Seeliger , Jan Sznajd , Andrew Judge , Joanna C. Robson2, Anthea Craven2, Matthew Jayne2, Lorraine Harper5 and was to identify salient dimensions of quality of life and perceived 2 problems of health status related to having AAV. The overall sample size Raashid A. Luqmani 1Department of Internal Medicine I, University of Jena, Jena, was determined by the point at which no new themes emerged from 2 interviews (saturation), and was also guided by a purposive sampling Germany, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK, framework to ensure that the broadest range of experiences possible 3 was captured. Thus, patients of both sexes, various ages, with all three Department of Internal Medicine, Jagiellonian University Medical School, Cracow, Poland, 4MRC Lifecourse Epidemiology Unit, forms of AAV, different disease durations, stages and extent of organ 5 involvement were included. Researchers (within and across research University of Southampton, Southampton and School of Immunity groups) independently scrutinized interview transcripts for relevant and Infection, University of Birmingham, Birmingham, UK themes. Themes identified from transcripts were then re-cast as candidate questionnaire items. Regular teleconferences maintained Background: Patients with systemic vasculitis suffer a delay in equivalence of methods and exchange of relevant themes. diagnosis which can result in significant organ failure and threat to Results: Fifty semi-structured interviews of patients with AAV were life. The Diagnostic and Classification Criteria in Vasculitis Study performed in Oxford (19), Ottawa (14) and Philadelphia (17) using (DCVAS) is an international multicentre project which allows us to standardized prompts and cues. After transcription and scrutiny, 60 examine time to diagnosis in different forms of vasculitis, healthcare distinct themes related to having AAV were identified, including systems and its potential predictors. symptoms (related to condition or treatment) and the ways in which Methods: We used preliminary data available from the DCVAS database these symptoms influenced patients’ ability to work, activities of daily up to June 2014, which comprised 1570 adult patients with primary living, engagement in social activities, and state of mind (see Table 1 systemic vasculitis. Delay in diagnosis was defined as time from onset of for the evolving conceptual framework). symptoms to diagnosis. We compared delay across the primary Conclusion: A list of themes and candidate items has been produced, systemic vasculitides by diagnosis; and in addition for GCA and drawn directly from patient experience, to inform the development of a ANCA-associated vasculitides (AAVs) by demographics and clinical PRO for AAV. Next steps include piloting the candidate questionnaire and diagnostic characteristics. We excluded all patients without items through cognitive interviews, surveying 500 patients to accurate data on time to diagnosis (n ¼ 826) or with a less than 50% produce an instrument with appropriate scale structure, measurement certainty of diagnosis (n ¼ 90), leaving 654 patients suitable for analysis. properties and scoring algorithms. This will be followed by a multi- Results: In 654 patients, the median delay (interquartile range) in days centred prospective validation study. was 31 (13–85) in GCA (n ¼ 230); 124 (64–337) in other large vessel Disclosure statement: J.C.R. has received consulting fees from GSK. vasculitides (n ¼ 40); 75 (32–75) in granulomatosis with polyangiitis R.L. has received consulting fees from GSK, Roche, Pfizer and (n ¼ 124); 52.5 (20.5–118.5) in microscopic polyangiitis (n ¼ 60); 72.5 Novartis. All other authors have declared no conflicts of interest. (15–205.8) in eosinophilic granulomatosis with polyangiitis (n ¼ 38); and 13.5 (9–28) in IgA vasculitis (n ¼ 54). Predictors of delay in GCA and AAV are summarized in Table 1. In both groups, a younger age was associated with a longer delay, whereas gender had no influence. In 315 TABLE 1. Evolving conceptual framework themes GCA, the presence of new polymyalgia-like symptoms (42.5 vs 24 Symptoms ANCA-associated vasculitis Treatment days, P ¼ 0.002), tongue or jaw claudication (36 vs 24 days, P ¼ 0.038) side effects and weight loss (51 vs 24 days, P ¼ 0.001) were associated with a Impact on Psychological Social Social Social General longer delay. Neither new headache nor visual symptoms influenced function impact contact perceptions role perceptions the delay. In AAV, limited disease (155 vs 61 days, P ¼ 0.002), eye and activities of health involvement (102 vs 60 days, P ¼ 0.002), and ENT involvement in

316 TABLE 1. Predictors of delay in diagnosis for GCA and AAV GCA (n ¼ 230) AAV (n ¼ 222)

Age, years n Median IQR P value Age, years n Median IQR P value <60 19 45.0 30.0–75.0 0.042 <40 45 65.0 31.0–194.0 0.017 60–79 175 31.0 13.0–92.0 40–54 46 66.0 66.0–120.0 0.028 80 36 21.5 8.0–60.0 a 55–70 85 90.0 90.0–180.0 0.003 >70 46 32.0 32.5–86.0 a Predictor/biopsy/blood test Present Absent P value Symptoms/manifestations Present Absent P value

n Median IQR n Median IQR n Median IQR n Median IQR New onset headache 183 31.0 13.0–83.0 47 32.0 6.5–99.5 P ¼ 0.676 Limited diseasea 24 155.0 70.0–155.5 198 61.0 26.0–138.0 0.002 Scalp tenderness 78 32.5 18.0–85.0 152 30.0 10.0–86.5 P ¼ 0.181 ENT involvement 114 77.5 34.0–162.0 84 36.5 19.0–101.5 0.001 Visual symptomsc 93 30.0 6.0–83.0 137 33.0 16.0–90.0 P ¼ 0.116 Eye involvement 54 102.0 36.0–137.0 168 60.5 26.0–124.5 0.002 Abnormal temporal artery 95 31.0 14.5–77.5 135 32.0 11.5–92.5 P ¼ 0.984 Skin involvement 56 78.5 29.5–169.5 166 65.6 27.0–155.0 0.515 Jaw or tongue claudication 99 36.0 17.0–92.5 131 24.0 10.0–81.0 P ¼ 0.038 Acute renal failure 66 71.5 26.0–140.0 140 74.5 31.0–161.5 0.651 PMR like symptomsd 82 42.5 21.0–102.0 136 24.0 8.0–63.5 P ¼ 0.002 Haemoptysis 53 49.0 28.0–124.0 169 71.0 28.0–162.0 0.546 Weight losse 75 51.0 22.0–107.5 155 24.0 8.5–70.5 P ¼ 0.001 Respiratory compromise 29 44.0 22.0–72.0 193 75.0 31.0–161.0 0.023 Neuropathy 63 82.0 20.5–159.5 159 62.0 30.5–160.0 0.980 Weight losse 92 75.0 36.5–139.5 130 61.0 22.0–162.0 0.283 Biopsy Yes No P value Biopsy Yes No P value

n Median IQR n Median IQR n Median IQR n Median IQR Performed? 194 31.0 12.0–81.0 36 37.5 14.0–104.0 0.589 Performed? 159 72.0 26.0–162.5 63 49.0 31.0–158.0 0.593 Positive? 127 31.0 12.0–81.0 67 31.0 15.0–80.0 0.941 Positive? 96 61.0 31.0–164.0 63 84.0 27.0–136.5 0.168 Blood test Present Absent P value Blood test Present Absent P value

n Median IQR — — — n Median IQR n Median IQR CRP <20 mg/l 54 28.50 14.0–68.0 — — — a CRP <20 mg/l 39 131.0 41.5–236.5 — — — a CRP 20–100 mg/l 88 31.50 8.0–90.0 — — — 0.935 CRP 20–100 mg/l 76 61.0 24.5–131.0 — — — 0.020 CRP >100 mg/l 66 31.00 15.0–77.0 — — — 0.754 CRP >100 mg/l 63 70.0 31.5–105.0 — — — 0.026 — ANCA MPO/PR3 175 72.0 31.0–160.0 32 72.5 25.0–175.0 0.719 aReference group; blimited to ENT or lung withour systemic features; cAmauroxis fugax, sudden visual loss, blurred vision; dinflammatory shoulder or hip-girdle pain or morning stiffness; e>2 kg. IQR: interquartile range. POSTER VIEWING III Thursday 30 April 2015 i173

patients without limited disease (77.5 vs 36.5 days, P ¼ 0.001) were Results: The performance of ACR criteria varied across the vasculitis associated with longer delay. Time to diagnosis in patients with types (Table 1). For classification, the average sensitivity was 69.9%: it respiratory compromise was shorter (44 vs 75 days, P ¼ 0.023), but not was excellent in GCA (96.5%), but poor in all other vasculitides in those with haemoptysis or progressive renal impairment. Neither (varying from 15.4% in MPA to 75.0% in IgA vasculitis). Overall performance of a biopsy nor its result contributed to delay in GCA or specificity for classification was high at 93.3% (88.3–99.4). In terms of AAV. Normal or mildly abnormal CRP was predictive of longer delay; diagnostic performance, sensitivity ranged from 14.96% in MPA to the presence of ANCA did not influence delay in AAV. 77.6% in GCA, with an overall sensitivity of 60.0%. Overall specificity Conclusion: Time to diagnosis was variable across different vasculi- was 88.6% (64.2–98.9%). tides. Younger age and certain phenotypes of GCA and AAV seem to be Conclusion: This preliminary analysis using data from DCVAS associated with a longer delay in diagnosis. The presence of PMR demonstrates that the sensitivity of the 1990 ACR classification criteria symptoms, weight loss and jaw claudication increased the delay to has declined drastically over the last two decades; overall, 30% of PSV diagnosis of GCA. In AAV, limited disease, eye or ENT involvement, or with existing ACR criteria remained unclassified. However the absence of high inflammatory markers contributed to delay; respiratory specificity of the criteria remains largely unchanged. A decline in compromise shortened delay. We need to be aware of these limitations sensitivity may reflect improved recognition of a wider spectrum of in our attempts to improve diagnostic outcomes in vasculitis. disease phenotypes aided by novel diagnostic tests such as ANCA. Disclosure statement: R.A.L. has received consultancy fees from Our results confirm previously published evidence of the poor GSK, Nordic and ChemoCentryx; and has received lecturing fees from diagnostic performance of ACR criteria and should further discourage Roche and Nippon Kayaku. All other authors have declared no their use for this purpose. The results emphasize the need for new conflicts of interest. classification and diagnostic criteria for systemic vasculitides. DCVAS will provide the largest population of patients with vasculitis collected to date to develop these new criteria. 317. RE-APPRAISAL OF THE 1990 AMERICAN COLLEGE OF Disclosure statement: The authors have declared no conflicts of RHEUMATOLOGY CLASSIFICATION CRITERIA FOR interest. SYSTEMIC VASCULITIS: ANALYSIS OF DATA FROM THE DIAGNOSTIC AND CLASSIFICATION CRITERIA IN VASCULITIS STUDY 318. PRELIMINARY ANALYSIS OF HISTOLOGICAL FINDINGS 1,2 1,3 1,4 IN GCA BIOPSY-POSITIVE PATIENTS RECRUITED INTO A Benjamin Seeliger , Andrew Judge , Jan Sznajd , Peter LARGE MULTICENTRE STUDY OF TEMPORAL ARTERY A. Merkel5, Richard A. Watts6, Ravi Suppiah7, Joanna C. Robson1, 8 1 1 ULTRASOUND VERSUS BIOPSY IN THE DIAGNOSIS OF GIANT Peter C. Grayson , Anthea Craven and Raashid A. Luqmani CELL ARTERITIS 1Nuffield Department for Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK, Surjeet Singh1, Andrew Hutchings2, Wulf Forrester-Barker1, 2Department of Internal Medicine I, University of Jena, Jena, Bhaskar Dasgupta3, Andreas Diamantopoulos4, Peter Lanyon5, Germany, 3MRC Lifecourse Epidemiology Unit, University of Malgorzata Magliano6, Brendan McDonald7, Konrad Wolfe8 and Southampton, Southampton, UK, 4Department of Internal Medicine, Raashid Luqmani1 Jagiellonian University Medical School, Cracow, Poland, 5Penn 1Nuffield Department of Orthopaedics, Rheumatology and Institute for Immunology, University of Pennsylvania, Philadelphia, Musculoskeletal Sciences, University of Oxford, Oxford, 2London PA, USA, 6Norwich Medical School, University of East Anglia, School of Hygiene and Tropical Medicine, London, 3Department of Norwich, UK, 7Department of Rheumatology, Auckland District Rheumatology, Southend University Hospital, Westcliff-on-Sea, UK, Health Board, Auckland, New Zealand and 8National Institutes of 4Department of Rheumatology, Hospital of Southern Norway, Health, NIAMS, Bethesda, MD, USA Kristiansand, Norway, 5Department of Rheumatology, Nottingham University Hospital, Nottingham, 6Department of Rheumatology, Background: In 1990 the ACR introduced criteria for the classification Stoke Mandeville Hospital, Aylesbury, 7Department of Pathology, of the primary systemic vasculitides (PSVs) that are widely accepted University of Oxford, Oxford and 8Department of Pathology, and applied in clinical studies. Advances in diagnosis (e.g. ANCA Southend University Hospital, Westcliff-on-Sea, UK testing) and better imaging has led to better distinction between PSV, potentially affecting the validity of these criteria. Though designed as Background: A temporal artery biopsy (TAB) showing giant cells, classification criteria they have been widely used as diagnostic tools active inflammation and intimal hyperplasia is the gold standard for despite evidence of their poor performance as such. We reappraised diagnosing TA, although a negative biopsy does not exclude it. We their effectiveness as classification and diagnostic criteria using large reviewed the histological features of TAB from a prospective 22 centre numbers of adult patients with vasculitis and comparator conditions study of patients with suspected TA (TABUL). included in the Diagnostic and Classification Criteria in Vasculitis Study Methods: Temporal artery biopsies were performed in all patients with (DCVAS). suspected TA from June 2010 to December 2013. All biopsies were Methods: We used preliminary data available from the DCVAS database examined by the local pathologist. We describe the key histological features. up to June 2014, comprising 1570 patients with PSV and 546 Results: Based on data from 399 patients [287 female and 112 male, comparators. We extracted individual ACR criteria from the dataset with a mean (S.D.) age 70.8 (9.6) and range of 47–96], of whom 397 and tested their performance in diagnosis and classification for GCA, received steroids, the mean time to biopsy (post-steroids) was 5 (3) Takayasu’s arteritis, granulomatosis with polyangiitis, eosinophilic days. The mean length of the biopsy was 11.7 (7.3) mm. Only 374 granulomatosis with polyangiitis, IgA vasculitis (Henoch–Scho¨ nlein), biopsies consisted of an artery (93.7%), from which 107 cases were PAN and microscopic polyangiitis (MPA). The clinical diagnosis supplied positive for GCA (28.6%). Of the 107 cases, 83 had internal hyperplasia by the recruiting physician (with recorded confidence >50%) was and 11 had both internal hyperplasia and arteriosclerosis in the intima. considered the gold standard and tested against the ACR criteria. Fragmentation in the internal elastic lamina was reported in 63 cases, 26 Clinical context specific comparators were used to assess the diagnostic cases reported fragmentation and reduplication. In 99.0% of biopsy- performance of the ACR criteria. For classification, we included only positive cases, inflammatory infiltrate were present, with transmural patients with biopsy-proven vasculitis (n ¼ 705, 598 with ACR criteria (38.3%) and media (19.6%) recorded as the predominant sites of defined vasculitis and 107 with another PSV). Because there was no inflammation. Giant cells were seen in 76 (71.0%). Completely occluded distinction between PAN and MPA in the original ACR criteria, we tested vessels were found in 24 cases, usually due to internal hyperplasia (in the PAN criteria for both entities separately. 18), although 5 had additional thrombus. Furthermore, 7 cases had

317 TABLE 1. Sensitivity and specificity of the 1990 ACR criteria as classification and diagnostic criteria Classification criteria Diagnostic criteria

Vasculitis n Sensitivity Specificity Vasculitis PSV, n Controls, n Sensitivity Specificity GCA 228 96.4 92.7 GCA 437 81 77.6 64.2 TAK 6 — — TAK 66 24 68.2 87.5 GPA 195 61.3 88.3 GPA 350 267 61.1 88.0 EGPA 32 59.4 99.9 EGPA 108 267 45.4 98.9 PAN 25 36.0 92.1 PAN 47 267 34.0 95.5 MPA 78 15.4 91.9 MPA 148 267 14.9 95.5 IgA vasculitis 61 75.4 93.3 IgA Vasculitis 78 228 70.5 90.4 Total 598 69.9 93.3 Total 1234 546 60.0 88.6 EGPA: eosinophilic granulomatosis with polyangiitis; GPA: granulomatosis with polyangiitis; MPA: microscopic polyangiitis; TAK: Takayasu’s arteritis. i174 Thursday 30 April 2015 POSTER VIEWING III

evidence of recanalization in at least one section of the biopsy. We number of positive biopsies (107/374) may reflect the low analysed the clinician’s initial assessment at baseline (prior to biopsy): index of suspicion of GCA in this group, technical difficulties in obtaining 99, 217 and 83 out of 399 cases were defined as possible, probable or an adequate sample, skip lesions or the effects of glucocorticoid therapy definite GCA: of these, 9 (9.1%), 57 (26.3%) and 41 (49.4%), in changing the biopsy result. Our findings highlight the need for a better respectively, had a biopsy consistent with GCA. diagnostic strategy for patients with suspected TA. Conclusion: Histological features in biopsy-positive patients with Disclosure statement: R.L. has received consulting fees from GSK, GCA are not confined to one form of inflammation. The most Roche, Pfizer and Novartis. All other authors have declared no common finding was transmural inflammation. The relatively low conflicts of interest. i175

E-POSTER ABSTRACTS

Methods: A 28-year-old man, who had recently moved to the UK from Pakistan, was admitted with fevers, posterior chest pain, dyspnoea, ABSTRACTS productive cough and weight loss of 12 kg over the preceding year. He had intermittent asthma-like symptoms for 2 years that were responsive to oral glucocorticoids. His blood tests revealed eosino- philia (9.92 109/l, more than 50% of the total white cell count) and a E01. FOUR UNUSUAL CASES OF PYOMYOSITIS: A CASE markedly elevated cardiac troponin level. His chest radiograph SERIES showed patchy airspace shadowing at the bases; ECG showed widespread ST changes; ECG showed severely impaired left ven- Tochukwu Adizie1, Jaya Ravindran1 and Shirish Dubey1 1 tricular function and a pericardial effusion. He became hypoxic and Rheumatology, University Hospitals Coventry and Warwickshire, received non-invasive ventilation, high dose oral prednisolone and Coventry, UK initial broad-spectrum antimicrobials to cover atypical/parasitic infec- tion. A full infective screen was negative. A chest CT scan showed Background: Primary pyomyositis is a rare infection of skeletal multi-lobar infiltrates together with bilateral pleural effusions and a striated muscle. It typically affects immunocompromised patients in pericardial effusion. Cardiac catheterization showed features of temperate climates. myocarditis. Subsequent investigations revealed normal ANCA titres Methods: We present four cases of pyomyositis: three in immunode- (including PR3 and MPO) and a cardiac MRI (gadolinium-enhanced) ficient patients and one in an immunocompetent young man. showed evidence of endomyocardial fibrosis. The patient had difficulty Results: Case 1: a 46 year old woman with common variable opening his right eye fully and evidence of partial ptosis and miosis. immunodeficiency was admitted with a 5 day history of right knee MRI of the head, neck and orbits showed mild enhancement swelling and fever. There was a large right knee effusion. Her CRP was surrounding the right optic nerve but no lesions within the sympathetic 180. MRI of the right knee revealed evidence of septic arthritis with a pathways. Neurology review confirmed the diagnosis of right-sided multiloculated abscess lying around the distal femur within the vastus Horner’s syndrome. He was treated with pulses of i.v. CYC followed by intermedius. She had an arthroscopy with open drainage. The fluid maintenance therapy with AZA. prednisolone doses were gradually was urea plasma positive on PCR. She received 12 weeks of antibiotic reduced. Horner’s syndrome subsequently resolved and his cardiac therapy with doxycycline, fucidin, azithromycin, flucloxacillin and co- and respiratory function improved significantly. trimoxazole. Case 2: A 30 year old woman with alcoholic liver disease Results: This patient had EGPA with cardiac, pulmonary and presented with neck stiffness, myalgia of her upper arms and fever. neurological involvement. Endomyocardial fibrosis can now be She had tenderness and restricted movement in the neck, left wrist detected with gadolinium-enhanced cardiac MRI scans, without the and left elbow. Her CRP was 179 and both RF and anti-CCP need for invasive endomyocardial biopsy. We have found only one antibodies were strongly positive. Ultrasound performed on both other case report of Horner’s syndrome in EGPA. This manifestation upper arms showed frank myositis and a collection within the left may result from vasculitis or eosinophilic infiltration of the vasa biceps consistent with pyomyositis. Aspiration of the left biceps was nervorum along the sympathetic pathway for pupillary innervation. arranged. PCR testing to the fluid identified the causative organism as Conclusion: EGPA has a variety of manifestations. Our patient had the Streptococcus pyogenes. She completed a 2 week course of i.v. unusual cardiac and neurological features of endomyocardial fibrosis meropenem and clindamycin and was discharged on oral amoxicillin and Horner’s syndrome. Patients with cardiac involvement are more and clindamycin for a further 2 weeks. Case 3: A 19 year old woman likely to be ANCA negative and have higher peripheral eosinophilia, was admitted with fever, right ankle and right calf pain with swelling whereas neurological involvement usually occurs in ANCA-positive following a course of UKALL chemotherapy regime for newly patients. Recognition and prompt treatment of vasculitic disorders is diagnosed B lineage acute lymphoblastic leukaemia. She also had vital, particularly where there are unusual manifestations or potentially neutropenia and thrombocytopenia. MRI of the lower limbs identified life-threatening organ involvement such as the cardiac involvement in discrete collections in the anterior and posterior compartments of the this patient. Our patient made an excellent recovery with no long-term right calf consistent with pyomyositis. The collection grew gentamicin- sequelae after almost 3 years of follow-up. resistant Escherichia coli sensitive to meropenem. She completed 4 Disclosure statement: The authors have declared no conflicts of weeks in total of meropenem and ertapenem. Case 4: A 32 year old interest. immunocompetent man from Kazakhstan presented with pain and swelling in left knee, left thigh tenderness and night sweats. Knee aspirate was unremarkable, but MRI of his left thigh showed evidence E03. A DIAGNOSTIC DILEMMA: A CLINICAL CASE OF of pyomyositis and an abscess, which was drained by the orthopaedic EXTRACRANIAL GIANT CELL ARTERITIS surgeons. Fluid culture grew Staphylococcus aureus sensitive to Amanda C. Hill1 and Sarah J. Evans1 flucloxacillin and he was given a total of 8 weeks with good clinical 1Rheumatology, Prince Philip Hospital, Llanelli, UK response Conclusion: Pyomyositis is rare and was first described in the UK in Background: GCA is the most common of the vasculitides and 1998. We report four recent cases from a single hospital. Our series predominantly affects the cranial branches of arteries arising from the highlights that pyomyositis in immunocompromised patients can aortic arch. It is managed with long-term glucocosteroid therapy to present in unusual anatomical locations, with atypical organisms. It treat and prevent complications of the disease. However, this can also occur in immunocompetent individuals. Several cases have represents a rare exception to the common difficulty in diagnosis been fatal; therefore, clinicians need to be vigilant for this uncommon and treatment lies. but increasingly recognized condition. Methods: A 62 year old female with PMR treated with prednisolone Disclosure statement: The authors have declared no conflicts of 20 mg was admitted to hospital for investigation of persistently raised interest. acute phase markers (CRP 216 mg/l, ESR 136 mm/h). She was systemically well with no organ-specific symptoms and she denied E02. EOSINOPHILIC GRANULOMATOSIS WITH symptoms of active PMR. Investigations excluded infection and there POLYANGIITIS (CHURG–STRAUSS SYNDROME) PRESENTING were no clinical stigmata to suggest vasculitis. Temporal artery biopsy WITH UNUSUAL CARDIAC AND NEUROLOGICAL FEATURES was negative. During subsequent review in clinic a significant discrepancy in blood pressure between arms was noted and Timothy D. Reynolds1 and Roopa Prasad1,2 accompanied by a left subclavian bruit. CT angiogram identified 1Department of Rheumatology, Bristol Royal Infirmary and thickening and stenosis of the proximal right and left brachial arteries, 2University of Bristol, Bristol, UK right subclavian and middle left subclavian arteries. A PET-CT later requested confirmed diffuse abnormal tracer uptake (grade 3) in the Background: Cardiac involvement in eosinophilic granulomatosis with thoraco-abdominal aorta and major superior mediastinal vessels; a polyangiitis (EGPA) has been reported in around 45% of patients and diagnosis of extracranial GCA was made. may account for as many as half of the deaths from the condition. Results: prednisolone caused marked mood disturbance (depression) Endomyocardial involvement is an unusual cardiac manifestation. and therefore MTX, AZA and LEF were tried to minimize total Neurological manifestations are widely reported but there are few glucocorticosteroid exposure but were associated with adverse reports of Horner’s syndrome arising in EGPA. effects. Tocilizumab 8 mg/kg was then commenced and after one i176 E-POSTER ABSTRACTS

treatment CRP and ESR had normalized, blood pressure equalized E05. INFECTIOUS PYOMYOSITIS CAUSED BY between both arms and the bruit disappeared. However, due to side STAPHYLOCOCCUS AUREUS effects of a facial rash and glossitis, the dose was reduced to 4 mg/kg Liubov Borukhson1, Irfan Khan1 and Vivek Rajagopal1 and was administered with hydrocortisone and chlorphenamine cover. 1 The patient continued to respond well and the prednisolone dosage Rheumatology, West Suffolk Hospital, Bury St Edmonds, UK was gradually reduced and eventually stopped 8 months after the initiation of tocilizumab therapy and she continues to do well 3 months Background: Infectious (tropical) pyomyositis is an acute, potentially later. life-threatening bacterial infection of skeletal muscles. It is endemic in Conclusion: This case describes an asymptomatic patient with tropical areas (hence the name). Despite this condition being relatively persistently raised acute phase markers who created a diagnostic uncommon in temperate climates, it is on the rise and is most challenge. Due to the original diagnosis of PMR, GCA was considered commonly seen in immunocompromised patients. The onset of but there were no cranial symptoms and she denied limb claudication pyomyositis is usually insidious, typically presenting as a focal pain. PET-CT was useful in demonstrating a large vessel vasculitis. A muscle infection, and carries significant morbidity without antibiotic recent systematic review identified 24 patients who had been given treatment. Staphylococcus aureus is cultured from an affected muscle tocilizumab for relapsing GCA. The standard dose given was 8 mg/kg in 75% of non-tropical cases. It usually arises from haematogenous every 4 weeks, but there was no reference to lowering this dose once spread. In spite of extensive muscle involvement, raised serum disease became controlled. We describe a case of a patient creatine kinase levels are paradoxically atypical. Only limited data successfully controlled on a dose of 4 mg/kg with no signs or are available regarding the diagnosis and management of this symptoms of relapse. Hence, this case further demonstrates the condition. success and efficacy of tocilizumab in the treatment of large vessel Methods: We present a case of a patient with S. aureus pyomyositis, vasculitis. who was successfully treated with linezolid. A 68 year old man Disclosure statement: The authors have declared no conflicts of presented with a seven day history of pain and weakness in both interest. thighs, proximal myopathy, weight loss and night sweats. He had been on 15 mg prednisolone for the previous 6 months for PMR. Upon examination, he had swollen tender palpable quadricep muscles bilaterally; the weakness was particularly evident in the hip flexors and E04. HEPATITIS E INFECTION IN INFLAMMATORY knee extensors. Inflammatory markers were considerably raised (white ARTHRITIS cell count 24.0, neutrophils 21.8, CRP 372, ESR 84 mm/h). Liver function tests were abnormal: bilirubin 10, alkaline phosphatase 221 Muhammad F. Kazmi1 1 IU/l and alanine transaminase 56 IU/l. Total creatine kinase was not Department of Rheumatology, Royal Hallamshire Hospital, Sheffield, elevated at 36 IU/l. Initial treatment with broad-spectrum antibiotics UK was not successful in resolving his illness. Results: MRI demonstrated symmetric inflammation involving the Background: MTX is the most commonly used DMARD for manage- proximal muscle groups of the pelvis and both thighs in keeping with a ment of inflammatory arthritis. As part of its monitoring, liver function non-specific inflammatory myopathy /polymyositis. An EMG was tests are regularly checked to ensure there is no liver damage. Very consistent with a proximal myopathy largely affecting the lower often in clinical practice, the liver function tests can become abnormal, limbs, with chronic features, slightly atypical for inflammatory myo- which results in attributing the abnormality to MTX, and various pathy. Muscle biopsy microbiology identified S. aureus sensitive to investigations are performed including checking for active HBV and flucloxacillin and linezolid. Infectious myositis secondary to S. aureus HCV infection. Although rare in developed counties, the possibility of was diagnosed. The inflammatory markers begun to normalize and the HEV infection must be kept in mind in patients on immunosuppression symptoms improved after the initiation of linezolid. In total, 2 months of when there is an unexplained sudden increase in liver enzymes which oral linezolid (patient was penicillin allergic) were required for the this case report illustrates. inflammatory markers to normalize and symptoms to resolve. Repeat Methods: We report two cases of abnormal liver function tests which MRI 3 months after the admission showed significant improvement of were detected as part of routine blood monitoring performed every the inflammatory changes in the pelvic and thighs muscle groups with 3 months due to being on MTX monotherapy. The first case is of a 68 no evidence of continuing myositis. Previous long-term steroid use year old woman with seropositive erosive RA for 8 years and had been may have led to suppressed immune response to infections in our on stable dose of 12.5 mg once weekly for last 6 years. It was noted patient. that she had greater than tenfold elevation of aspartate and alanine Conclusion: We encourage clinicians to maintain an index of aminotransferase levels and moderate elevation of alkaline phospha- suspicion for infectious pyomyositis in patients with myalgia and tase. She felt a bit tired but otherwise well. The other case is of a 32 fever in absence of significant elevation of muscle enzymes. Linezolid year old Caucasian man who was on stable dose of 20 mg once appears to be an effective treatment for S. pyomyositis, which in the weekly for 2 years for PsA. He also felt more tired with reduced case of our patient led to a complete recovery. appetite and was found to have a >10-fold elevation in alanine Disclosure statement: The authors have declared no conflicts of transaminase and aspartate transaminase levels. interest. Results: In both cases, MTX was stopped and it took around 2 months for the liver enzymes to go back to previous normal levels. In both cases, there was no history of prior travel abroad when the liver tests E06. A CASE OF LYMPHOMA PRESENTING AS SACROILIITIS became abnormal. Initial non-invasive liver screen was unremarkable along with normal liver US and HBV and HCV test serology; both Tochukwu Adizie1 and Sophia Y. Khan1 patients were subsequently diagnosed with having HEV infection 1Rheumatology, Solihull Hospital, Solihull, UK which was confirmed by positive PCR detection and positive IgM result. In both cases, following discussion with hepatologist MTX was Background: The association between rheumatic conditions and reintroduced once the liver enzymes had become normal with no lymphoproliferative disorders have been well recognized but axial evidence of abnormality in liver enzymes later on. HEV infection involvement is uncommon. happens rarely in UK but the incidence is going up due to consumption Methods: We report the case of a 45 year old woman who presented of undercooked pork and travel to developing countries. There are no with inflammatory back pain, was initially diagnosed as AS, but reports of chronic HEV infection following immunosuppression and subsequently developed a left sacral mass with histology positive for outcome of HEV infection is usually favourable. diffuse B cell lymphoma of the germinal type. Conclusion: These cases highlight the importance of arranging Results: A 45 year old, fit and active woman with a previous history of investigations looking for HEV infections even if there is no history of plantar fasciitis presented with a 6 month history of low back pain, travel abroad and not attributing all liver enzyme abnormalities to MTX. stiffness and night pain. The pain worsened with activity and was The diagnosis of acute hepatitis E should be considered in patients relieved by diclofenac. There was also a history of neuropathic pain with inflammatory arthritides with acutely raised liver enzymes who are radiating down her left leg. She was initially reviewed by spinal on immunosuppressants. surgeons as an outpatient and MRI of the lumbar spine and SI joints Disclosure statement: The author has declared no conflicts of was requested, which revealed extensive bilateral sacroiliitis. Initial interest. blood tests revealed a CRP of 2 mg/l and ESR of 8 mm/h, with normal E-POSTER ABSTRACTS i177

immunoglobulins, full blood count, renal function and liver function. E08. BELIMUMAB: A MORE TARGETED THERAPY FOR She was then referred to Rheumatology. Her back pain continued to DISEASE CONTROL AND REDUCTION OF progress in severity over the subsequent 6 months with the patient IMMUNOSUPPRESSANT BURDEN IN SLE reporting marked distress due to pain, and difficulty mobilizing. In Hem R. Sapkota1, Deborah Symmons2 and Ian Bruce3 addition, she began to suffer night sweats, weight loss, poor appetite 1 2 and difficulty swallowing, as well as a large left-sided cervical mass. Rheumatology, Blackpool Victoria Hospital, Blackpool, Department of Rheumatology, Macclesfield District General Hospital, Repeat blood tests at this point showed an ESR of 54 mm/h, CRP of 3 62 mg/l, alkaline phosphatase 163 IU/l, albumin 29 g/l, platelets Macclesfield and The Kellgren Centre for Rheumatology, Central 456109/l, lymphocytes 1.23 109/l. As the severity of pain was Manchester University Hospitals, Manchester, UK greater than expected for a spondyloarthropathy, another MRI of the lumbar spine and SI joints was requested, which revealed a soft tissue Background: Warts and molluscum contagiosum are opportunistic mass involving the left SI joint and extending anteriorly and posteriorly viral skin lesions which can be extensive and are notoriously resistant with further multiple, well-defined bony lesions throughout the sacrum, to standard treatment in immunocompromised patients resulting in pelvis and upper femurs bilaterally. These appearances were significant discomfort and psychological distress. We report a case of consistent with a differential diagnosis of myeloma or metastatic SLE where belimumab was added to enable dose reduction of other malignancy. Subsequent CT of the thorax, abdomen and pelvis background immunosuppression and which resulted in successful showed a neck swelling adjacent to the thyroid gland and multiple eradication of plantar warts. para-aortic lymph nodes, but no clear primary malignancy was Methods: We report the case of a 29 year old white British woman identified. Tumour markers, including CA-125, CEA, CA-153 and CA who first presented with SLE in 2002, characterized by haemolytic 19-9, were negative, while serum electrophoresis and serum free light anaemia and thrombocytopenia (Evan’s syndrome). chain findings were normal. Biopsy of the neck lesion showed only Results: Management of her initial disease included high dose reactive lymphoid tissue but biopsy of the sacral mass confirmed a steroids and AZA, with subsequent splenectomy. Additional features diffuse large B cell lymphoma germ cell subtype. of her SLE have been arthritis, Raynaud’s phenomenon with severe Conclusion: We report a rare case of primary sacral, diffuse B cell digital ischaemia, severe photosensitivity, alopecia and recurrent lymphoma of the germinal cell type. The patient presented initially with haemolytic anaemia. Her serology included positive ANA, anti- sacroiliitis and progressed to develop a sacral mass. Sacroiliitis can be dsDNA antibodies and low C3 and C4 complement during flares. In a paraneoplastic phenomenon and should be considered as a July 2006, she developed myositis which did not respond to MMF but differential diagnosis especially in cases of uncharacteristically improved with s.c. MTX. She required 30 mg/week of MTX along with severe, progressive low back pain that become significantly disabling prednisolone 8–10 mg daily and HCQ 200 mg daily to control her over the course of 6–9 months. disease. Any reduction in steroids or MTX resulted in a flare of her Disclosure statement: The authors have declared no conflicts of myositis and/or haemolytic anaemia. In addition to her SLE, she also interest. had recurrent infections (salmonella gastroenteritis, streptococcal pharyngitis and shingles) and developed severe plantar warts, perianal and genital molluscum contagiosum. The former was resistant to E07. COMPLETE RESPONSE TO INTRAVENOUS topical therapies and covered her entire forefoot causing her to limit CYCLOPHOSPHAMIDE IN A GIANT CELL ARTERITIS her walking and restricting her work to desk duties. In view of the patient’s immunological status during disease flares, we added Eisha K. Omar1 and Bridget Griffiths1 1 belimumab (Benlysta) 10 mg/kg monthly in July 2013 to her treatment Rheumatology, Freeman Hospital, Newcastle upon Tyne, UK regime with the stated aim to reduce her steroids, MTX and her overall immunosuppressive burden. From October 2013 to April 2014, we Background: GCA involves the major branches of the aorta with a tapered her MTX to 15 mg weekly and her prednisolone to 7.5 mg daily predilection for the extracranial branches of the carotid artery. The without a disease flare and plantar warts have resolved completely and signs and symptoms of GCA can be classified into four subsets: she is able to walk without restriction. cranial arteritis, extracranial arteritis, systemic symptoms and PMR. Conclusion: Belimumab is a targeted monoclonal antibody against B Methods: We report a case of a man who presented with symptoms of lymphocyte stimulator and offers more targeted control of SLE than all four subsets. He deteriorated very quickly but made a full recovery traditional immunosuppressive agents. In this case, it allowed after treatment with i.v. methylprednisolone and CYC. significant immunosuppressive sparing to her regime that facilitated Results: A 76 year old man presented in June 2014 with a 3-month clearance of severe plantar warts. history of polymyalgic symptoms, and a 1- to 2-week history of Disclosure statement: The authors have declared no conflicts of temporal headaches, jaw claudication, scalp tenderness, weight loss interest. and intermittent blurred vision in both eyes. On the day of presentation to ophthalmology, he developed a non-resolving blurred patch of in his right visual field with an ESR of 123 mm/h and a CRP level of 91 mg/l. E09. A CASE REPORT: GRANULOMATOSIS WITH He had arteritic ischaemic optic neuropathy. A temporal artery US was POLYANGIITIS PRESENTING AS A TEMPORAL ARTERITIS consistent with GCA. He was started on aspirin and three doses of 1 g i.v. methylprednisolone (MP) were given daily. On the next day, he was Hem R. Sapkota1 and Hanadi Sari-Kouzel1 commenced on 60 mg of oral prednisolone. A few hours later he 1Rheumatology, Blackpool Victoria Hospital, Blackpool, UK developed confusion, incoordination, dysarthria and left hemiparesis. Brain CT and MRI scans showed ischaemic lesions in the anterior and Background: Granulomatosis with polyangiitis (GPA) is a multisystem posterior circulation. Subsequent magnetic resonance angiography granulomatous and necrotizing vasculitis which predominantly affects showed multifocal extracranial, predominantly vertebral and possible the respiratory and renal systems. Ocular involvement can be seen in intracranial arterial involvement, likely due to vasculitis. Further up to 50–60% of the affected patients and can be a presenting imaging to investigate the cause of a weak left radial pulse showed symptom. GPA can involve any structure in the eye including the eye generalized disease in left axillary artery, thickened left subclavian lids, sclera, cornea, choroid, retina and optic nerve. We report a rare artery and stenosed origin of left brachial artery. ECG was normal. case of GPA presenting with anterior ischaemic optic neuropathy ANCA and all other immunology tests were negative. Inflammatory mimicking a TA. markers gradually normalized within 10 days of presentation. He was Methods: We report the case of a 65-year-old patient developed commenced on i.v. CYC at a dose of 10 mg/kg with i.v. MP at 6.6 sudden onset visual loss in his right eye. mg/kg at 2-weekly intervals for first three pulses, and then at 3-weekly Results: He was immediately referred to ophthalmology by his general intervals for the next three. He has finished these six pulses and made practitioner with a provisional diagnosis of TA. He also complained of a full recovery except for feeling that his balance is slightly impaired at jaw pain, weight loss and malaise. The ophthalmological examinations times. We plan to give him a total of nine pulses and then switch to oral confirmed anterior ischaemic optic neuropathy with no other demon- maintenance treatment. His oral prednisolone dose is being tapered strable orbital disease. He was immediately started on i.v. methyl- (now at 15 mg/10 mg on alternate days) and his recent PET-CT scan prednisolone followed by oral high dose prednisolone as per standard on low-dose steroid has not shown any evidence of active vasculitis. protocol with the initial diagnosis of TA. Inflammatory markers were Conclusion: This is the first case to our knowledge where a patient very high with a CRP of 209 mg/l and an ESR of 102 mm/1st hour. with GCA deteriorated and developed stroke a day after high dose i.v. Routine chest X-ray (CxR) later revealed cavitating lung lesions. At that steroids and then made an almost full recovery with i.v. MP and CYC point, on specific questioning, he volunteered a few months’ history of without any side effects. nasal blockage and discharge. He however denied shortness of Disclosure statement: The authors have declared no conflicts of breath, haemoptysis, arthralgia or vasculitic rash. His cANCA was interest. positive. CT of the sinus demonstrated anterior septal perforation with i178 E-POSTER ABSTRACTS

inflammatory changes; CT of the chest revealed multiple nodules with the cartilage layer. Contrary to this in gout, MSU crystals appear on the cavitations and temporal artery biopsy showed mild non-specific superficial margin of the cartilage giving the characteristic double vasculitis, not typical of TA. The diagnosis of GPA was made and he contour sign. MSU crystals can also be seen as multiple aggregates of was commenced on pulse CYC with reducing regime prednisolone. hyperechoic deposits within the SF giving a characteristic snowstorm The weight loss, malaise, nose bleeds and inflammatory markers all appearance. This snowstorm appearance is rarely seen in pseudog- improved with treatment, as well as lung lesions on subsequent out. In fact, to the best of our knowledge this phenomenon has never imaging. Visual loss persisted in his right eye but left eye remained been reported before and we report the first ever case. unaffected. Methods: We report the case of an 84 year old man was admitted with Conclusion: GPA should be a differential diagnosis for a TA swollen and painful sternoclavicular joints in addition to a polyarthritis presenting with a sudden onset visual loss. This is important as the affecting his hands, wrists, shoulders, knees. This was associated with treatment and prognosis of these two vasculitides is not the same. ongoing pyrexia. Disclosure statement: The authors have declared no conflicts of Results: His inflammatory markers were significantly elevated. His interest. CRP was greater than 200 mg/l. An autoimmune screen, viral screen, serum urate and blood cultures were unremarkable. US of the sternoclavicular joint showed hyperaemia with marked synovial E10. SULPHASALAZINE-INDUCED DRUG REACTION AND thickening. Hyperechoic calcific deposits were seen in the SF EOSINOPHILIA AND SYSTEMIC SYMPTOMS surrounding these joints in a characteristic snowstorm appearance. Klara Morsley1, Shilpa Selvan1, Alan Steuer1 and Jenny Watkins1 Synovial fluid aspiration at this joint was technically difficult so a knee 1Rheumatology, Wexham Park Hospital, Slough, UK aspirate was performed which confirmed a diagnosis of acute pseudogout. He was treated with a combination of a reducing Background: Drug reaction with eosinophilia and systemic symptoms regime of low-dose steroids and colchicine and his symptoms (DRESS) is a rare idiosyncratic drug reaction, typically developing up improved dramatically. Three months on he has been weaned off to 8 weeks after starting the precipitating agent. Features include a steroids and is on low-dose colchicine. His symptoms have not maculopapular rash, fever, hepatitis and haematological manifesta- returned. tions, most commonly eosinophilia and leucocytosis. It is a clinical Conclusion: This case also further highlights the importance of US to diagnosis requiring the presence of an offending drug. Reported rheumatologists in the detection of crystal related arthropathy. precipitants include anti-epileptics, allopurinol, antibiotics and sulpho- Disclosure statement: The author has declared no conflicts of namides. It may progress to visceral involvement with a mortality of up interest. to 10%. Methods: We present here two cases of patients with PsA who E12. COEXISTENT ANKYLOSING SPONDYLITIS AND developed DRESS secondary to SSZ. SYSTEMIC LUPUS ERYTHEMATOSUS Results: In case 1, a 48 year old man with PsA was started on SSZ on 1 a titrating dose. One month later, he presented acutely with a 10-day Mervat Eissa 1 history of fevers and a widespread pruritic rash, beginning on his chest Rheumatology & Rehabilitation, Cairo University, Cairo, Egypt and spreading to his limbs and face. He was pyrexial and had a widespread maculopapular rash with thickened, tender skin. Blood Background: The coexistence of SLE and seronegative spondyloar- tests revealed a mild leucocytosis and eosinophilia with impaired renal thropathy is extremely rare. To our knowledge there are only eight function and deranged liver function. Blood and stool cultures were cases reported. We describe here another case of this coexistence. negative. SSZ was immediately stopped and i.v. fluids, broad- Methods: We report the case of a male patient, 45 years old, from spectrum antibiotics, topical emollients and steroids were prescribed. Egypt, with family history of RA (his mother). In 1997, he complained of Despite these measures, his symptoms did not improve. Additionally, inflammatory low back pain, associated with neck pain and morning his eosinophil count rose to 1.9 109/l, and alanine transaminase to stiffness for 30 min. Physical examination showed positive clinical tests 489 IU/l. Prednisolone 15 mg daily was started, and over several days for sacroiliitis with Scho¨ ber test increased only 3 cm. Laboratory tests both his rash and blood counts improved. He was discharged on a showed ESR of 65 mm/h, CRP 1.89 mg/dl (normal up to 0.5) and tapering dose of prednisolone but was readmitted with similar clinical negative HLA-B27. X-ray on SI joints showed bilateral sacroiliitis grade features several days later, improving on a course of 30 mg VI. MRI of SI joints revealed bilateral sacroiliitis with narrowed joints prednisolone. In case 2, a 23 year old woman with PsA was started space with bony overbridged and subchondral and subarticular on SSZ on a titrating dose. After 7 weeks, she was admitted with a marrow changes on both sacral and iliac sides. In 2006, routine pruritic erythematous rash, sore throat and pyrexia. She had stopped laboratory investigations showed repeatedly elevated albumin in urine. taking SSZ 5 days previously but her symptoms worsened. She Estimation of 24 urinary proteins was 1.7 g/24 h, creatinine of 92 mmol/l became erythrodermic and was treated with i.v. fluid and topical (71–115) and total IgA of 2.38 g/l (0.63–4.84). An ANA test was positive emollients and steroids. Cervical lymphadenopathy and mild eosino- homogeneous 1/160 and an anti-dsDNA test was positive 38.6 IU/ml philia was noted. Over the next 24 h, she developed an increasingly (index <10). Renal biopsy was done in 2006 and showed proliferation severe systemic inflammatory response and was started on i.v. of mesangial cells. The interstitial tissue and tubules appears steroids and antibiotics. Despite these measures, she became unremarkable. This was consistent with LN class II active. The patient haemodynamically unstable and was transferred to high dependency was diagnosed with SLE. He received oral prednisone 2 mg/day care for further management. She subsequently developed visceral tapered gradually to 5 mg with angiotensin-converting-enzyme inhi- involvement with hepatic and renal impairment. She had a relapsing- bitor, with improvement of proteinuria. The patient reported increasing remitting disease course that gradually resolved over several weeks. lower back pain and stiffness, and his spinal movements had Conclusion: SSZ is commonly used in the treatment of PsA. These deteriorated. He was therefore started on etanercept 50 mg weekly, cases illustrate the importance of awareness of this rare, yet potentially with improvement, but in March 2012 he developed hypertension and fatal side effect. a flare of proteinuria (1.98 g/24 h), with ESR of 97 mm/h, negative CRP 3 3 Disclosure statement: The authors have declared no conflicts of haemoglobin of 14 g/l, total lymphocyte count of 7.7 10 /mm , 3 3 interest. platelet count of 372 10 /mm , creatinine of 0.9 mg/dl, alanine transaminase of 52 U/l, C3 of 131 mg/dl (75–175) and C4 of 20 mg/dl (10–40). Anti-dsDNA was positive, 95.6 IU/ml (index <20). Another E11. ACUTE PSEUDOGOUT IN A PATIENT PRESENTING renal biopsy was done in April 2012, revealing LN class IV. Oral WITH SNOWSTORM APPEARANCE ON ULTRASOUND prednisone was raised to 60 mg/day and ciclosporin A was started (175 mg/day) with improvement. Qasim Akram1 1 Results: The patient meets the Assessment in Spondyloarthritis North West Deanery, Rheumatology Department, Salford Royal International Society criteria for the classification of axial spondyloar- Foundation Trust, Manchester, UK thritis and also Systemic Lupus International Collaborating Clinics classification criteria for SLE. Background: We describe the case of an elderly man diagnosed with Conclusion: This case report confirms that two inflammatory joint acute pseudogout who was shown to have snowstorm appearance of diseases may coexist. It is suggested that the rarity of the coexistence CPPD crystals on US. This is not a common observation. Several of SLE and AS in the same patient might depend on the fact that the sonographic appearances suggestive of CPPD crystals have been B27 antigen rarely exists in combination with the DR2 or DR3 antigens, described. These include thin, hyperechoic bands within the cartilage which are associated with SLE. layer and hyperechoic rounded or amorphous shaped areas typically Disclosure statement: The author has declared no conflicts of in the triangular ligament of the wrists and the menisci of the knee. In interest. addition, homogeneous hyperechoic nodular or oval shaped hyper- echoic densities are seen in tendons. Crystals usually appear within E-POSTER ABSTRACTS i179

E13. ABSTRACT WITHDRAWN increased pain and a diffuse SCJ swelling. She was treated for presumed RA flare and overlying cellulitis with a short course of oral steroids and antibiotics. A further review 2 weeks later noted persistence of symptoms and patient was referred for a routine E14. AN UNUSUAL PRESENTATION OF CYTOTOXIC STORM rheumatology opinion. Her medical records revealed a history of sero- Jessica Bowen1, Claire Maxton1 and Tim Blake1 negative non-erosive RA diagnosed 10 years ago, which resolved after 1Rheumatology, Sandwell and West Birmingham Hospitals NHS 1 year of DMARD therapy with no further joint disease. She also has Trust, Birmingham, UK asthma, renal cell carcinoma treated with nephrectomy and a family history of diabetes and leukaemia. She is an ex-smoker (30 pack- Background: A 27 year old woman presented with persistent pyrexia, years) with minimal alcohol intake and works as a priest. Her vomiting, headache, dizziness and rigours. This occurred following a medications include a beclomethasone inhaler, loratadine and prolonged recent trip to India where she was diagnosed and treated amitriptyline. On examination, the patient was apyrexial and haemo- for Kikuchi disease from which she had made a full recovery 11 months dynamically stable. The left SCJ was warm, swollen and tender with before this admission. Examination revealed pyrexia (37.88), tachy- reduced active movement of the ipsilateral shoulder. Blood inflamma- cardia (119 bpm) and an erythematous, papular, blanching rash on the tory markers were elevated (CRP 216 mg/l, ESR 108 mm/h, white cell extremities with no palp ble lymph nodes. Systemic examination was count 11.4). RA serology was negative. Urgent US revealed severe otherwise unremarkable. inflammation surrounding the left SCJ. Blood, urine and SF culture Methods: A literature review was conducted to guide the diagnosis were negative. Patient was admitted for i.v. antibiotics. There was and review the diagnostic criteria. initial good clinical and biochemical improvement, but progress Results: Investigations revealed normal white cell count [6.3 (4– plateaued a week into treatment. A further MRI and multidisciplinary 11 109)] and neutrophils [4.78 (1.7–7.5 109)], as well as mildly team review concluded that there was SCJSA with osteomyelitis. An reduced lymphocytes [0.99 (1–4 109/l)] and platelets [147 109/l US -guided aspiration and synovial biopsy was performed, which grew (150–450 109/l)]. There were deranged liver function tests: albumin Staphylococcus aureus. Intravenous antibiotics were continued for 3 31 (35–50 g/l), ALP 180 (20–130 U/l), alanine transaminase 86 ( <41 U/l) weeks before switching to oral antibiotics. The patient was then and elevated lactate dehydrogenase (LDH) of 1886 (<225 U/l). Plasma discharged for follow-up in clinic. She recovered with normalization of sodium was reduced to 131 (133–146 mmol/l) and urea was 1.7 biochemical markers after 13 weeks of combined antibiotic therapy (2.5–8 mmol/l). Peripheral blood film showed atypical lymphocytes and without any complications. neutrophils with band form and toxic granulation. As part of a septic Conclusion: SCJSA can present as a routine primary care referral to screen five blood cultures were taken and showed no growth. the rheumatology clinic. A high index of suspicion is needed to ensure Serology revealed a positive IgG for CMV and EBV (CMV PCR was prompt diagnosis and prevention of complications. Presentations can <500 copies/ml). The patient was negative for hepatitis, HIV and be subacute without traditional signs of sepsis. malaria. ANA, ANCA and complement levels were normal. ESR was Disclosure statement: The authors have declared no conflicts of mildly elevated [13 (1–12) mm/h] but CRP was raised [151 (<1) mg/l]. interest. Coagulopathy was evident with increased international normalized ratio 1.3 (0.85–1.25), prothrombin time 19.4 s (11.8–17.4 s), partial E16. TAKAYASU’S DISEASE AND ULCERATIVE COLITIS: thrombin time 51.1 s (23.2–40.2 s) and an activated partial thrombo- CASE REPORT AND REVIEW OF THE LITERATURE plastin time ratio 1.60 (0.74–1.30), potentially indicating infection. CT imaging showed multiple para-aortic, iliac and mediastinal nodes and Joseph J. Heath1, Joanna Cuttell2 and Marwan Bukhari1,2 bilateral pleural effusions with a 12.5cm spleen (enlarged). 1Lancaster Medical School, Lancaster University and 2Rheumatology Conclusion: In light of her known rheumatological condition, Department, University Hospitals of Morecambe Bay NHS unrelenting pyrexia with elevated ferritin, liver enzymes, triglycerides Foundation Trust, Lancaster, UK and LDH, coagulopathy and central lymphadenopathy, a diagnosis of macrophage activation syndrome was made. This was in keeping with Background: A 51 year old woman presented with pain below her the diagnostic criteria set out by the Haemophagocytic elbow, myalgia, tenderness and occasional numbness of her distal left Lymphohistocytosis Trial in 2004. Macrophage activation syndrome arm, there were no symptoms of claudication in the upper limbs. On is more usually found associated with juvenile idiopathic arthritis and examination, there was decreased blood pressure with a distal can carry a high mortality rate. There are case reports of an difference of more than 15mmhg in the radial artery on the left only association with Kikuchi disease. Fortunately the patient in this case but no difference in the brachial artery pressure and other pulses in the recovered with oral CSs, but it reminds us that a rheumatological left upper limb. No clavicular bruits of the upper limbs were present. diagnosis should be considered in cases of pyrexia of unknown origin Neurology was intact. When investigated, magnetic resonance where there is no evidence of infection. To update an old saying; angiography did not show evidence of a proximal lesion and US hooves do not always mean horses. showed radial arteritis that did not extend proximally and a marked Disclosure statement: The authors have declared no conflicts of luminal Doppler signal in the blood vessel wall. Inflammatory markers interest. were elevated, ESR was 34 mm/h and CRP was 26.2 mg/l; thus, a clinical diagnosis of Takayasu’s arteritis was made. Concomitantly, the patient developed rectal bleeding and flexisigmoidoscopy with biopsy E15. STERNOCLAVICULAR JOINT SEPTIC ARTHRITIS IN revealed acute inflammation of the distal colon, making a diagnosis of THE RHEUMATOLOGY CLINIC: HIGH CLINICAL SUSPICION concomitant ulcerative colitis. Treatment with systemic CSs has NEEDED ameliorated both diseases with normalization of the inflammatory markers (ESR fell to 4 mm/h and CRP fell to <5.0 mg/l). Chong Seng Edwin Lim1 and Karl Gaffney1 Methods: This study is a case report. 1Rheumatology, Norfolk and Norwich University Hospital, Results: On review of the literature there have been 53 cases reported Norwich, UK of the association between the two diseases. The incidence of Takayasu’s arteritis in the general population is 0.26 per 100 000 Background: Sternoclavicular joint septic arthritis (SCJSA) is a rare people annually. Although the primary target vessel for Takayasu’s clinical entity usually associated with predisposing factors such as i.v. arteritis, the aorta may occasionally be spared. The incidence of drug use, infection at a distal site, immunosuppression, trauma and ulcerative colitis in the general population is 10 per 100 000 people pre-existing joint disease. Patients often present acutely to the annually. The coexistence of both in so many cases implies causality. emergency department, with further care managed independently by Indeed, a recent study in Tokyo, Japan proposed that Takayasu surgeons. patients could have ulcerative colitis in up to 6.1% of cases. Methods: We report the first case of SCJSA to present in a Conclusion: This case is unique in that the Takayasu’s disease spared rheumatology clinic via a routine, non-emergency referral and the aorta, while all others have involved the aortic arch. This should successfully treated without surgical intervention. raise awareness of the link between bowel disease and vascular Results: A 56 year old female presented to the rheumatology clinic disease. With a postulation that there is a spectrum of auto- with a 4-week history of worsening left shoulder pain with restricted inflammatory disease that affects different endothelial surfaces (e.g. movement, poor sleep and feeling unwell despite regular analgesia aortitis and retroperitoneal fibrosis) and that extra vigilance on links and treatment initiated by her general practitioner (GP). This started between inflammation in different endothelial surfaces should occur. with a sudden onset of non-traumatic left shoulder ache which Additionally, the classification of some vasculitides could be progressed to anterior chest pain around the sternoclavicular joint reconsidered. (SCJ) within 24 h. She presented to her GP for stronger analgesia but Disclosure statement: The authors have declared no conflicts of returned 2 days later with reports of overnight rigours and chills, interest. i180 E-POSTER ABSTRACTS

E17. EASILY MISSED: RESISTANT POSTURAL AS in 1984. He also had severe disease and DAS of 4.6 with significant ORTHOSTATIC TACHYCARDIA SYNDROME IN A functional disability. In recent years, has been treated successfully with HYPERMOBILE YOUNG MAN SSZ and etanercept. He was diagnosed with follicular lymphoma in 2005 and it was decided to treat him conservatively and monitor him Timothy Shao Ern Tan1, Evelyn Li Ping Lim1 and Pauline Ho2 1 2 for progression. Manchester Medical School, University of Manchester and The Methods: We are reporting two cases of follicular lymphoma in AS Kellgren Centre for Rheumatology, Manchester Royal Infirmary, patients, under the care of one rheumatologist. Manchester, UK Results: Studies have clearly demonstrated that autoimmune disease can predispose patients to non-Hodgkin’s lymphoma. In a nationwide Background: Postural orthostatic tachycardia syndrome (POTS) is Swedish case-control study, in the absence of TNF inhibitor treatment, characterized by the onset of orthostatic symptoms with a rise in heart there was no increased risk of developing follicular lymphoma. rate of 30 beats/min within 10 min of standing or an absolute heart rate However, some studies have shown a higher frequency of peripheral of >120/min following tilt-table testing (gold standard investigation) at an blood IL-21 positive follicular helper T cells in patients with AS. Another angle of about 60–70 degrees to the horizontal. It is highly associated study found that follicular T-helper cell aberration can lead to with joint hypermobility syndrome (JHS) or Ehlers–Danlos syndrome pathologies such as the lymphoma found in these patients. hypermobility type as a form of autonomic dysfunction. Individuals Conclusion: The occurrence of two cases of follicular lymphoma in AS affected are mainly aged between 15 and 50 years and predominantly patients, within such close proximity, highlights the strong link in disease female. Often under-recognized, POTS may mimic other conditions such pathogenesis of autoimmune disease and malignant lymphomas. as anxiety or neurocardiogenic syncope. Management of POTS is Whether the genetic make-up of AS patients can predispose them to difficult, as there is limited evidence of the potential therapeutic benefits follicular lymphoma is yet to be studied, and could be extremely relevant from both pharmacological and non-pharmacological approaches. in furthering our understanding of AS. There is hope that if we and our Methods: A 23-year-old man presented to the rheumatology clinic patients are aware of associated risks when diagnosed with AS, we may with hypermobile joints and a 6-month history of recurrent palpitations, be able to avoid, or more promptly manage, a malignancy diagnosis. light-headedness and lower limb weakness upon standing without any Disclosure statement: The authors have declared no conflicts of associated syncope, which improves on recumbence. However, his interest. functional ability has been impaired. Previous encounters of similar episodes were diagnosed as chronic fatigue syndrome. His medical history includes childhood blackouts, depression and FM for which E19. RAPID RESPONSE TO BENZBROMARONE FOR GOUT appropriate medications are taken. IN A RENAL TRANSPLANT PATIENT Results: On clinical examination, his heart rate increased from Eisha K. Omar1 and Suleman Khan1 80/min [blood pressure (BP) 147/97 mmHg] when supine to 146/min 1 (BP 142/87 mmHg) when standing for 10 min. He was also noted to Rheumatology, Freeman Hospital, Newcastle upon Tyne, UK have hypermobile joints in all limbs and cervical spine, fragile skin, bilateral pes planus and thoracic scoliosis, all consistent with JHS. His Background: Gout in solid is a challenging clinical blood work-up (full blood count, urea and electrolytes, RF, ANA, CRP, problem which involves potential drug interactions. Benzbromarone in liver function tests, thyroid function tests) was unremarkable. transplant patients has not been used much in recent years due to Transthoracic ECG revealed laxity of mitral valve and surrounding potential hepatotoxicity, although the risk is low in Europe. ligaments. Furthermore, tilt-table testing at 60 degrees displayed a Methods: We report a case of a 46 year old man with a history of a significant heart rate increment from lying (53/min, BP 113/68 mmHg) cadaveric renal transplant in 1992 secondary to GN, who presented to to standing (140/min, BP 124/86 mmHg). As such, JHS-associated us in 2011 with episodes of ankle synovitis spreading onto his wrists POTS was diagnosed. He was started on a trial of midodrine 2.5 mg and relieved with short courses of oral prednisolone. Ultrasound scan and sodium chloride 600 mg for 3 months but these worsened his showed ankle effusions with double contour sign, serum urate was symptoms. Thereafter, fluoxetine 20 mg and labetalol 50 mg were tried 0.60 mmol/l with an estimated glomerular filtration rate of 43.2 ml/min/ 2 but to no avail. Hence, he was managed conservatively, aimed at 1.73m and he was diagnosed as gout. He was on AZA and ciclosporin symptom control. Occupational and physiotherapy support was also for his transplant and thus it was decided not to commence him on sought with muscle-strengthening exercises. Advice was also given urate-lowering therapy (URT) because of potential drug interactions. about optimizing fluid and salt intake. Results: He re-presented in December 2013 with worsening and more Conclusion: A high index of suspicion of POTS should be made in frequent symptoms of gout affecting other joints as well and tophus hypermobile patients presenting with orthostatic intolerance. formation. His serum urate was 631 mmol/l and it was decided to Diagnosis can be complicated due to overlapping features with other commence him on URT. Benzbromarone 50 mg once daily was started conditions. It is imperative that POTS be recognized and treated in February 2014 as other agents would have interacted with his promptly as symptoms can be debilitating. Thus far, no single therapy immunosuppressants. Within a month, his serum urate lowered to has been proven effective. Non-pharmacological measures should first 278 mmol/l, gouty attacks became less frequent and tophus started to be considered in otherwise fit and healthy individuals. In more severe resolve. Monthly urate levels remained <300 mmol/l without renal or symptoms or associated vasovagal syncope, pharmacological (e.g. hepatotoxicity. Ciclosporin levels remained stable except for a single fludrocortisone, selective serotonin re-uptake inhibitors, pyridostig- high reading of 282 in April 2014. He was reviewed in June 2014 when mine) intervention should be considered. A multidisciplinary holistic his serum urate levels were 299 mmol/l. care must be employed in treating non-autonomic features (e.g. Conclusion: Thus, benzbromarone can be quite rapidly effective fatigue, musculoskeletal damage) and tailored to patients’ needs. clinically as well as biochemically within a month in renal transplant Disclosure statement: The authors have declared no conflicts of patients without any adverse effects. Close monitoring of renal, interest. hepatic and immunosuppressant drug levels is mandatory though. The case also reiterates the efficacy of benzbromarone in lowering hyperuricaemia in ciclosporin-treated renal transplant patients Disclosure statement: E18. ANKYLOSING SPONDYLITIS AND FOLLICULAR The authors have declared no conflicts of LYMPHOMA interest. Joanna Cuttell1, Marwan Bukhari1 and Joseph Heath1 1Rheumatology, Royal Lancaster Infirmary, Lancaster, UK E20. ABSTRACT WITHDRAWN

Background: When two patients with AS, under the care of the same consultant rheumatologist received a diagnosis of follicular lymphoma, E21. ACUTE GOUT ATTACKS ASSOCIATED WITH LOWER LIMB suspicions were raised as to the link between these two specific MYOPATHY pathologies. A 62 year old man, whose AS was diagnosed in 1999, had very advanced AS. He had complete fusion of the thoracic and lumbar Mahdi Abusalameh1 and Susie Earl1 spines. His Disease score was 7.16 indicating severe disease, he had 1Rheumatology, Royal Devon & Exeter Hospital, Exeter, UK severe pain and was functionally limited. He was considered a good candidate for biologics and was started on etoricoxib and adalimumab Background: The differential diagnosis for acute myopathy is wide in 2009, to which he responded very well. He presented in 2012 with and includes inflammatory muscle diseases, infections, drug-induced shortness of breath on exertion. Lung function tests showed an as well as endocrine disorders. obstructive lung pathology and further investigation of the chest with Methods: A 56-year-old male patient, who presented to our CT revealed an incidental finding of a T11 lesion. Surgical removal of rheumatology clinic with a 10-year history of episodic leg weakness, the lesion and biopsy revealed a follicular lymphoma for which the however remains well in between episodes. He describes the patient received radiotherapy. A 70 year old man was diagnosed with weakness to be profound in his legs to the degree that sometimes E-POSTER ABSTRACTS i181

he has difficulty walking and climbing stairs. There were no other gradually improved and monitoring of CK demonstrated an improve- symptoms on systemic review. He is also noted to suffer from ment to 277 U/l within 12 days. The patient is now being followed up as recurrent attacks of gout for the past few years. The interesting fact is an outpatient and further uric acid lowering treatments are being that the episodes of leg weakness do seem to be clearly related to considered. His statin has been restarted. Given the onset of when he develops a flare of his gout and are associated with symptoms after commencing febuxostat, absence of any other intermittently raised creatine kinase (CK), up to 1000 IU/l in one plausible aetiology and resolution of rhabdomyolysis after withdrawal occasion. At the time of his clinic review, he was just recovering from of the drug, the diagnosis of febuxostat-induced rhabdomyolysis was an acute attack of gout in his right index finger few weeks before. On made. examination, he had power of >4 at the knee extensors and on hips Conclusion: Febuxostat is an extremely rare cause of rhabdomyo- flexion; otherwise the rest of his neurological and general examination lysis, with only one other case being reported in the literature. In any was normal. patient presenting with symptoms of rhabdomyolysis, all current Results: Initial blood tests showed intermittent raised CK during his medications should be reviewed and any potentially offending drugs leg weakness episodes. Uric acid was raised at 498 mmol/l, and ANA, withdrawn once the diagnosis has been confirmed. This case ENA and ANCA were negative. EMG has shown a peripheral mild emphasizes the importance of considering febuxostat as one of demyelinating neuropathy but no evidence of a myositis. Vastus these offending medications. intermedius biopsy has shown some focal deposition of membrane Disclosure statement: The authors have declared no conflicts of attack complex in capillaries which can be seen in inflammatory interest. muscle disease however there were no other features of myositis in particular there was no evidence of HLA upregulation or any abnormalities on electron microscopy. He was treated with allopurinol E23. RECURRENT SERONEGATIVE SYMMETRICAL between mid-1990s and 2000; however, he stopped taking that due to SYNOVITIS WITH PITTING OEDEMA INVOLVING UNILATERAL a lack of effect, although it is not clear whether dosing was optimal. His HAND acute attacks of gout have been treated with indomethacin and lately Gayatri Mittal1 naproxen, but he never had colchicine. 1Rheumatology, Royal National Orthopaedic Hospital, Middlesex, UK Conclusion: To our knowledge, this is the first case of gout causing an intermittent myopathy which resolved upon cessation of the acute Background: Remitting seronegative symmetrical synovitis (RS3PE) attack. Our recommendation has been to recommence allopurinol typically presents as sudden onset pain and swelling of both hands aiming for a uric acid level of <300 mmol/l. We have advised against predominantly affecting elderly men and usually demonstrates a good using colchicine. Acute myopathy has been reported to be associated responsiveness to short-term treatment with glucocorticoids. with colchicine use especially with impaired renal function; however, Unilateral hand involvement with RS3PE is rare and likely to be our patient never had colchicine, nor been on any other drug that might attributed to cellulitis or venous obstruction. Recognition of this cause myopathy. One case report described a patient with gout and unusual manifestation of RS3PE is important to institute steroid peripheral neuropathy that improved with the lowering of the serum therapy to facilitate rapid resolution of the symptoms. uric acid level, but in the absence of muscle involvement. In the Methods: A 69-year-old male patient presented to rheumatology clinic absence of any known potential cause of myopathy in our patient, with 5 weeks’ history of acute onset swelling, redness, mild pain in his there is a clear association of his episodes of leg weakness with the right hand and difficulty in the hand grip and function. His symptoms flare ups of his gout. failed to improve with three courses of antibiotics. His general health Disclosure statement: The authors have declared no conflicts of was good and there was no past history of gout, psoriasis, eye or interest. bowel inflammation, preceding trauma or infection. He smoked pipe and did not drink alcohol. His past medical history included right total hip replacement and mild gastritis, which was treated with E22. A CASE OF RHABDOMYOLYSIS INDUCED BY omeprazole. FEBUXOSTAT THERAPY IN A PATIENT WITH Results: On examination, there was non-tender pitting oedema over HYPERURICAEMIA AND CHRONIC RENAL TRANSPLANT the dorsum of his right hand. His right forearm was also swollen but not DYSFUNCTION tender. The left hand examination was unremarkable. Both the radial, Leanne Gray1, Lesley Ottewell1 and Marwan Bukhari1 brachial and carotid pulses were well felt. There were no palpable 1Department of Rheumatology, Royal Lancaster Infirmary, NHS, cervical or axillary lymph nodes. ANA, RF and CCP were negative; ESR Lancaster, UK was 22 mm/h, CRP was 20 mg/l, serum urate was 0.19 and a chest X- ray was within normal limits. His symptoms responded dramatically to Background: Hyperuricaemia is a well-documented, debilitating the first dose of 30 mg of prednisolone, which was tapered off over the complication of chronic kidney disease (CKD). Even in asymptomatic 4 weeks before discontinuation. The swelling over the hand and cases, it is reported as an independent risk factor for both progression forearm resolved completely with the short-term steroid treatment. of CKD and cardiovascular disease. Furthermore, in renal transplant RS3PE is a rare entity, which classically presents as involvement of patients hyperuricaemia has been shown to reduce long-term allograft both the upper extremities and is thought to be distinct from RA and survival. Treatment of gout in these patients is often difficult as some PMR. It may occasionally represent a paraneoplastic syndrome. uric acid lowering medications have nephrotoxic profiles while others Conclusion: Unilateral RS3PE is uncommon and described in handful cause toxicity through interaction with immunosuppressant therapies, case reports in literature, some of which include individuals with which are used in transplant patients. Febuxostat, an orally adminis- neurologic disorders with the involvement of the unaffected extremi- tered, non-purine xanthine oxidase inhibitor, is now recommended in ties. RS3PE should be included in the list of differential diagnoses of the ACR guidelines as a first-line treatment for gout. Furthermore, pain and swelling affecting unilateral hand. studies have shown favourable efficacy in urate-lowering properties as Disclosure statement: The author has declared no conflicts of compared with allopurinol, as well as a desirable safety profile in interest. patients with both established chronic kidney disease and renal transplants. E24. MYOSITIS FOLLOWING VACCINATION: AN Methods: We describe a rare case of rhabdomyolysis induced by UNEXPECTED RISK OF TRAVEL febuxostat therapy in a patient with chronic transplant dysfunction chronic kidney disease stage IV. We reviewed the patient case notes and Fiona Hayes1, Asad Khan1, Bernadette Lynch1 and Frances Borg1 performed a literature search for use of febuxostat in hyperuricaemia. 1Rheumatology Department, Southend University Hospital NHS Results: A 63 year old male patient, with known chronic kidney Trust, Westcliff-on-Sea, UK disease and history of two previous renal transplants, was referred to the rheumatology team due to recurrent episodes of gout. Urate levels Background: Drug-induced myositis is well described in medical were persistently higher than 500 U/l despite treatment with sulphin- literature, with a variety of agents implicated. We describe a case pyrazone (100 mg daily). Management options were limited due to following vaccination for HAV and typhoid in preparation for travel presence of renal impairment and co-existing AZA treatment. In order abroad; this has not previously been documented as a causative to achieve symptomatic control and reduce urate levels, it was agent. The patient recovered well, without the need for immunosup- decided to replace AZA (100 mg daily) with MMF (500 mg twice daily), pressive treatment. before commencing febuxostat (80 mg daily) under colchicine cover. Methods: A 21 year old student with a previous history of cervical Three weeks later, the patient presented to his general practitioner dysplasia [cervical intraepithelial neoplasia (CIN 1) 1] and polycystic with general malaise and widespread myalgia. On examination, there ovarian syndrome presented to the acute medical take with a history of was tenderness in the thighs. Initial creatinine kinase (CK) was subacute onset bilateral quadriceps pain and weakness, which had 14 515 U/l. Immediate management involved rehydration and with- rapidly progressed until she required a wheelchair to mobilize; she had drawal of both febuxostat and Atorvastatin. The patient’s symptoms similar but less severe symptoms in her arms. Examination revealed i182 E-POSTER ABSTRACTS

symmetrical proximal muscle tenderness and weakness affecting the elevated CSF cell count, Borrelia serology was sent. Initial tests were legs more than arms. Systemic examination, including skin, was positive for IgM Borrelia antibodies, prompting a two week course of otherwise unremarkable. Careful history elicited vaccination for HAV i.v. ceftriaxone. Detailed Borrelia results (Centre for Applied and typhoid within the preceding fortnight, but no other symptoms or Microbiology, Porton Down) were negative in both serum and CSF. recent changes in usual activity to suggest another cause. A 6-month interval MRI series found an additional T2 brain lesion, Investigations demonstrated creatine kinase (CK) of 1980 IU/l with no confirming the patient’s diagnosis of MS (single clinical event with MRI evidence of macro-CK on further testing. Spirometry was normal, as interval change). Her Raynaud’s symptomatology has improved but was EMG testing a few days after presentation. Full blood count, urea she experiences mild residual paraesthesiae. She is not currently a and electrolytes, liver function tests, thyroid function tests, immuno- candidate for MS disease-modifying therapy. globulins, viral screen, inflammatory markers and bone profile were Conclusion: Although allodynia is recognized as a presenting essentially normal apart from a marginally low vitamin D, and raised symptom of MS, no previous reports of MS presenting with aspartate transaminase at 55. Troponin T was normal, and subsequent Raynaud’s exist. autoimmune profile, including extended myositis screen was also Disclosure statement: The authors have declared no conflicts of within normal range. MRI of the thighs showed subtle increased signal interest. on the short Ti inversion recovery sequence within the left lateral thigh muscles. Biopsy of vastus lateralis was carried out, with no evidence E26. ATYPICAL HIP PAIN: IS IT ISCHIOFEMORAL of glycogen storage disease or inflammatory myopathy, although this was carried out 9 days after initial presentation, by which time the IMPINGEMENT? patient, and the CK titre had improved markedly. Given the history of Gayatri Mittal1, Jason Parry2 and Asif Saifuddin3 CIN, a transvaginal US scan and cervical biopsies were performed, 1Rheumatology, 2Physiotherapy and 3Radiology, Royal National which showed no concerning features. The patient recovered Orthopaedic Hospital, London, UK spontaneously, without the need for immunosuppression and 2 weeks after leaving hospital CK had normalized. Background: Hip pain is a common presentation in rheumatology Results: Drug-induced myopathy may be medicated by direct clinic. Its cause however may remain unclear in approximately 30% of myotoxicity or immunologically mediated. Typical onset is within patients. With the increasing use of arthroscopy and MRI, some of the weeks to a few months after exposure, and resolution occurs generally previously unidentified causes have been included in the differential within the same timeframe. Over 150 drugs have been described to diagnosis of hip pain. Although frequently described in orthopaedics cause myopathy, but a literature search did not reveal any previously and radiology, ischiofemoral impingement (IFI) is relatively less known reported cases following HAV /typhoid vaccination. Although biopsy in rheumatology. It was first reported in 1977 in three patients with was normal, the previous absence of muscle symptoms, temporal persistent hip pain after hip surgery and subsequently in patients relationship, lack of alternative cause and clinical course (spontaneous without history of preceding surgery or trauma. We herewith report a recovery within a few weeks) strongly suggest drug-induced disease. case of an amateur hockey player who was successfully treated with Conclusion: This is the first reported case of myositis associated with physiotherapy with significant improvement in her IFI-related hip pain. HAV and typhoid vaccination. When taking a history, clinicians should Methods: A 52-year-old female patient presented to rheumatology ensure that a drug history includes recent vaccinations. with a 10-year history of bilateral hip pain and stiffness. Her symptoms Disclosure statement: F.H. has received payment from Roche for had particularly worsened in the preceding year. The hip pain was now delivering an educational talk. All other authors have declared no constant (at times it woke her from sleep) and was accompanied by conflicts of interest. significant early morning stiffness. She had discontinued hockey and yoga due to the hip pain. The findings on examination included mildly painful internal rotation at the hips and localized tenderness over both E25. UNILATERAL RAYNAUD’S PHENOMENON AS THE the trochanteric bursa. MRI of her hips showed possible mild hip PRESENTING FEATURE OF MULTIPLE SCLEROSIS synovitis bilaterally, a small left anterior labral tear, bilateral gluteus Sarah E. V. Wright1, Alistair Lewthwaite2, Michael R. Douglas2 and medius tendinopathy, a tiny effusion in the right greater trochanteric Karen Douglas1 bursa and bilateral IFI, with marked reduction of the space between 1Department of Rheumatology and 2Department of Neurology, the ischium and the lesser trochanter with prominent oedema and Dudley Group of Hospitals NHS Foundation Trust, Dudley, UK some atrophy of the traversing quadratus femoris muscles (QFM). The acute phase reactants, RF, CCP and chest X-ray were unremarkable. Background: RP is characterized by episodic peripheral vasospasm As she did not wish to take NSAIDs, she was treated with causing cold, painful and discoloured extremities. RP is typically physiotherapy alone with a significant improvement in her symptoms symmetrical and may be primary or secondary to a CTD. Multiple over the next 12 weeks. sclerosis (MS), a chronic inflammatory disorder of the CNS, presents Results: IFI syndrome is defined as hip pain caused by the narrowing with a diverse range of neurological symptoms and signs. of the space between the ischial tuberosity and lesser trochanter with Methods: We present a case of sudden onset unilateral Raynaud’s as entrapment of the QFM. Patients with IFI generally present with the initial symptom of MS. gradual onset hip, deep posterior thigh or gluteal pain and may also Results: A previously well 45 year old non-smoking female, taking no suffer from snapping sensation, crepitation, or locking in the hip joint. medications, presented with an acutely painful, cold, numb and weak MRI has been the gold standard diagnostic test for IFI syndrome. The right hand. The hand was dusky and blue; however, brachial and radial cause of abnormal narrowing of the IF space may be congenital, pulses were present. She was in sinus rhythm with normal heart positional, due to a wider positioning of ischial tuberosities in females sounds and no bruits: all other limbs were normal. She had normal or acquired abnormalities such as fracture or osteotomy involving the nailfolds, no digital ulceration or features of a CTD or vasculitis. lesser trochanter, OA, enthesopathy of the proximal hamstring Ultrasound found patent large vessels of the right upper limb. After insertion. The relative benefit of conservative versus surgical manage- 10 h the patient’s symptoms resolved spontaneously. The vascular ment of IFI remains unclear. No definitive treatment has been team commenced nifedipine, simvastatin and aspirin, suspecting recommended, other than excision of the lesser trochanter. microvascular vasospasm. She was discharged awaiting a magnetic Conclusion: IFI although is less widely recognized, should be resonance angiogram (MRA) and referred to rheumatology. At considered in the differential diagnosis of atypical hip and or buttock rheumatology assessment 2 weeks later, the right hand remained pain. cool and the patient had suffered three further milder ischaemic Disclosure statement: The authors have declared no conflicts of episodes. MRA demonstrated subtle compression of both subclavian interest. arteries upon arm elevation: this was unlikely to be of significance. Further questioning revealed a 2-month history of cool/tingling E27. THE GREEK FOOT: IS IT A MYTH OR REALITY? AN sensations in her right hand and foot with mild grip difficulties. The EPIDEMIOLOGICAL STUDY IN GREECE AND CONNECTIONS patient was admitted for iloprost infusions and gained symptomatic TO PAST AND MODERN GLOBAL HISTORY relief. With the exception of a weakly positive ANA and a polyclonal raised IgM of 6.63 g/l, investigations including; full blood count, Periklis Vounotrypidis1 and Polyxeni Noutsou2 clotting, CRP, ANCA, ENA, cryoglobulins, anti-cardiolipin antibodies, 1Rheumatology Department, 424 General Military Hospital, lupus anti-coagulant, complement levels, hepatitis, HIV, syphilis Thessaloniki, Greece and 2Faculty of Humanities and Social serology, X-rays (chest, thoracic inlet and cervical spine), ECG and Sciences, Open University of Cyprus, Nicosia, Cyprus US abdomen were normal/negative. A neurology review suggested an MRI head and cervical spine, identifying an inflammatory lesion in the Background: According to classical taxonomy and nomenclature in right side of the cord at C5. A lumbar puncture found a normal Arts, there are three major forms of foot, characterized as Egyptian, cerebrospinal fluid (CSF) protein and glucose, an elevated white cell Roman and Greek, with an estimated incidence in the global count of 16/ mm3 and CSF-specific oligoclonal bands. In view of the population of 70%, 25% and 5%, respectively. In medical terms, the E-POSTER ABSTRACTS i183

Greek foot is described as a deformity or Morton’s toe. An extension of respondents, and was the therapy most commonly asked about in the above classical taxonomy adds the Celtic and German type of foot. outpatients. It is also reported that 90% of Ainu people in North Japan exhibit Conclusion: CAM is commonly used by rheumatology patients, but Morton’s toe. The purpose of the study is to capture the morphological often this is not disclosed in rheumatology outpatient consultations. features of the foot under the classical taxonomy in Greek population. Disclosure statement: The authors have declared no conflicts of Methods: One hundred and sixty-three subjects (male/female 76/87), interest. participated voluntarily in the study after written consent was obtained. Subjects enrolled by three working places, where it is possible to find people from different regions of Greece: a hospital, a military academy E29. GAP BETWEEN SELF-MANAGEMENT NEEDS AND and a women’s monastery. Morphology of foot was assessed clinically RESOURCES AVAILABLE FOR PEOPLE WITH ARTHRITIS and classified into the three types. The Greek nationality of the COULD BE MET BY ARTHRITIS ACTION MEMBERSHIP participants was confirmed and place of birth was recorded as well as Wendy Holden1, Alpa Virdi2 and Richard Congdon1 the presence of past or current symptoms in lower limbs. SPSS for 1Arthritis Action, Eastbourne, East Sussex and 2Spotlight Medical Windows, version 17.0 was used for the statistical analysis. Pearson Research, Rochester, Kent, UK chi-squared and Fisher’s exact test were applied appropriately for comparisons between groups. Background: 2014 NICE guidelines on OA emphasize a holistic Results: 56.4% of the study population originated from Macedonia, approach with self-management strategies including advice on while the 43.6% from other geographic regions of Greece. We exercise, weight management, fitness and manual therapy. These observed that 62% of men and 32% of women in this cohort exhibit guidelines recognize gaps in current NHS provision. Arthritis Action is the Greek type of foot (P ¼ 0.028). Overall, almost half of the population a membership charity which encourages self-management strategies (51.7%) exhibits the Egyptian and the Greek (46%) type of foot and a to improve the quality of life for people with arthritis, and commis- minority the Roman type (2.5%). The male/female ratio in the sioned a market research study to better understand the needs of examined population were 17.8% and 33.7% for the Egyptian type, people with arthritis and the views of the clinical and NHS community 0% and 2.5% for the Roman and 28.8% and 17%, for the Greek type, dealing with people with arthritis in order to widen the membership and respectively (P < 0.001). We also observed that five subjects (3%) awareness of the Charity’s programme presented mosaicism with one foot having the Greek and the other the Methods: In July 2014, an online quantitative survey of 769 people Egyptian type of foot. Furthermore, 26% of men and 23% of women with self-reported arthritis identified from a national database, plus 11 had a long period of symptoms in the lower extremities. in-depth qualitative telephone interviews with general practitioners Conclusion: The study confirms the increased incidence of Greek (GPs) and public health professionals were completed. Patients were type of foot in the Greek population. The ratios of this particular feature asked their beliefs about arthritis, including self-management and between genders in the study cohort reveal the inheritance by an X- social isolation, their behavioural patterns including exercise and diet, linked trait. This observation renders the characterization medical and their experience of current services for people with arthritis and deformity or even Morton’s toe improper, as the feature indicates future preferences. Healthcare professionals were asked about care phylogenetic origin. The connection to Celtic foot and Ainu people in pathways and key needs for people with arthritis, local provision and North Japan is also discussed. their thoughts about self-management strategies for people with Disclosure statement: P.V. has received funding from the Hellenic arthritis. Rheumatology Society. The other author has declared no conflicts of Results: 769 people with self-reported arthritis completed question- interest. naires. 393 reported OA, 204 RA or other inflammatory arthritis, 180 type of arthritis unknown. 76% used painkillers but only 39% felt that this was the best way of managing their arthritis pain. 35% reported depression or very low mood and 42% felt scared for the future E28. HOW COMMON IS COMPLEMENTARY AND because of their arthritis. 37% felt that doctors and the NHS did not do USE IN RHEUMATOLOGY? enough to help them with their arthritis and social isolation was very Michael A. Clynes1, Woan Hui Wong1 and Elaine Dennison1 common. 93% knew that staying active with arthritis was important 1MRC Lifecourse Epidemiology Unit, Southampton General Hospital, and 50% said that it was vital to be able to speak to others about their Southampton, UK condition. If available, 70% were highly likely to try exercise classes, 59% weight management advice and 65% self-management training. Background: Recent systematic reviews have suggested that use of Among GPs and public health professionals, several themes emerged. complementary and alternative medicine (CAM) is becoming more Some saw pain management purely in terms of painkillers. All widespread, especially in rheumatology. Accurate recording of use of appreciated the role of self-management for arthritis, especially such medication is very important, as some CAM therapies, for psychosocial support, weight management and exercise but acknowl- example herbal medicine, may interact with prescribed medication edged patchy service-provision for arthritis compared with other such as MTX. We surveyed the prevalence of use of CAM by chronic diseases such as diabetes. rheumatology patients attending outpatient clinics in Southampton Conclusion: There is a gap between the perceived needs of people and sought to investigate the knowledge of, and attitudes to, CAM with arthritis and what the NHS currently offers. NICE guidelines on among rheumatologists of different age, grade and sex. both OA and RA emphasize self-management strategies which are not Methods: 300 consecutive patients with various rheumatology widely available. Arthritis Action is a membership-based charity which conditions agreeing to participate in this study were recruited from offers for a small annual fee, individualized self-management strate- outpatient clinics in Southampton General Hospital. Each participant gies including advice on exercise, diet, some free physical therapies completed a short questionnaire detailing CAM usage, specifying the and pain management for people with arthritis plus support to reduce types of CAM they used. We asked whether patients had disclosed social isolation. Membership of Arthritis Action could bridge the gap use of these therapies to their rheumatologist. In addition rheumatol- between the self-management needs of people with arthritis and what ogists and nurse practitioners completed questionnaires that assessed the NHS currently offers. their knowledge of, and attitudes toward, CAM and their usual practice Disclosure statement: The authors have declared no conflicts of of recommending it to patients. interest. Results: The mean age of respondents was 56.9 (S.D. 15.9) years; 69% were female and 58% had a diagnosis of inflammatory arthritis. Of E30. INFECTION SCREENING PRIOR TO STARTING ANTI- these 300 rheumatology patients, 123 (41%) had used CAM. There TUMOUR NECROSIS FACTOR TREATMENT: A STUDY OF was no significant difference in age between CAM users and non- LOCAL PRACTICE users (57.5 (S.D. 16.6) years vs 55.9 (15.4) years). Respondents reported using up to 7 CAM therapies, with a median use of 2.2. The Jeremy G. Royle1, Pradip Nandi1, James Taylor1 and Rachel Jeffery1 1 mean age of respondents who had tried acupuncture was 60 (S.D. 15) Rheumatology, Northampton General Hospital, Northampton, UK years; by contrast, it was 46 (S.D. 16) years among those who had used energy therapy. Fourteen (11.4%) patients who used CAM reported Background: It is standard practice in the Rheumatology department using Chinese herbal medicine. Fifty-eight (47.2%) patients reporting to perform an infection screen prior to the initiation of anti-TNF in all CAM use had used glucosamine and chondroitin. Nearly half of the patients. This is to screen for tuberculosis with a chest X-ray and a patients did not tell their rheumatologists about their CAM usage. The tuberculosis (TB)-spot test, and tests for HBV, HCV and HIV. most common reason cited was that the rheumatologists had not Serological testing for varicella zoster virus antibodies is also enquired specifically. Of the 33 rheumatology practitioners surveyed, performed. A dedicated biologics clinic with specialist nurse input 63.6% were female, and over half were 40–59 years old. Consultants was implemented in 2009 in conjunction with a proforma to monitor and nurse practitioners reported that they often recommend acu- this process. More recently specialist pharmacy input has been puncture; glucosamine/chondroitin was the CAM most familiar to included in the clinic. i184 E-POSTER ABSTRACTS

E30 TABLE 1. Percentage of patients being screened for infection prior to anti-TNF Treatment, 2008–2009 Chest X-ray, % TB-spot test, % HIV, % HBC, % HCV, % VZV antibodies, % Total number of patients 2014 94 94 94 100 100 81 16 2013 98 83 52 60 62 47 60 2012 93 68 43 85 77 60 53 2011 96 21 0 21 21 19 47 2010 95 9 0 4 2 0 56 2009 96 0 0 4 4 0 48 2008 85 11 0 11 11 0 27 TB: tuberculosis; VZV: varicella-zoster virus.

Methods: The pharmacy database was used to identify all the patients without any recall or risk assessment. This highlights the need for staff who have been started on anti-TNF therapy between April 2008 and and patient education about the guidelines and the need for the April 2014. Patient numbers were cross referenced with the online implementation of a robust recall programme. letter store to confirm identity. The pathology database was then Disclosure statement: E.M. has received honoraria from Pfizer, Roche interrogated. Any aspect of the screen was considered valid if and AbbVie. All other authors have declared no conflicts of interest. performed within 6 months of the start date of therapy. Results: The results are summarized in Table 1, the percentage of patients being screened for infection prior to anti-TNF treatment E32. THE RISE AND FALL OF SEROPOSITIVE RHEUMATOID 2008–14. 307 patients were identified as starting anti-TNF therapy in ARTHRITIS: EXPOSURE TO CADMIUM IS A PLAUSIBLE the defined period. The number of patients started on anti-TNF therapy EXPLANATION FOR THE NATURAL HISTORY OF varied each year from 27 to 60, with 16 commenced on treatment in SEROPOSITIVE RHEUMATOID ARTHRITIS 2014 to date. The number of chest X-rays has remained stable since David Hutchinson1 2009 (92–98%). Other components of the screen have shown 1Rheumatology Department, Royal Cornwall Hospital, Cornwall, UK improvement since 2008. Screening was lowest in 2009 but has increased yearly since. Screening fell in 2013 but has continued to Background: Seropositive RA is thought to be a contemporary disease. improve. Testing rate of HBV and HCV has reached 100%, and testing The first description of RA occurred in 1804, and examination of skeletal for HIV has reached 94%. TB-spot testing has reached 94%. remains in Western Europe has failed to demonstrate evidence of Serological testing for Varicella Zoster antibodies is the lowest with erosive RA prior to this date. Seropositive RA is now far less prevalent only 81% being screened. than a generation ago. Cigarette smoking has emerged as a key Conclusion: Screening of patients in 2008 and 2009 was low but since environmental trigger factor for seropositive RA. However, a third of 2010, practice has improved considerably. Since the introduction of women and 10% of men with seropositive RA have never smoked. the specialist biologics clinic and screening proforma, the number of Studies suggest that seropositive RA is both more prevalent among the patients being screened has increased each year, with the exception working class and in working class districts independent of the smoking of 2013. With the addition of specialist pharmacy input, screening has history. Additionally, industrial pollution and welding are risk factors for continued to improve. Further modifications to practice and to the seropositive RA. Studies have identified cigarette smoking as the most proforma are being undertaken with the aim of screening 100% of important environmental risk for cadmium exposure. Cadmium is a patients. component of industrial pollution and is emitted as ultra-fine particles Disclosure statement: The authors have declared no conflicts of when fossil fuels are combusted. Welding fumes contain a high interest. cadmium content and welders are at risk of cadmium toxicity. Methods: A PubMed search of the medical literature was undertaken to explore whether cadmium is a plausible aetiological agent for the E31. LONG-TERM BISPHOSPHONATE THERAPY: REVIEW development of seropositive RA. OF TWO GENERAL PRACTICES PRESCRIBING AND Results: Cadmium was first discovered in the 18th century, cadmium MONITORING levels in pre-19th century skeletal remains have been shown to be 5-fold lower than in contemporary skeletal remains. Environmental exposure Chitra Nair1, Tagore Bojja2 and Elizabeth MacPhie3 peaked in the mid-19th century and has reduced by 30% in the last 1Ash Tree House Surgery, Ash Tree House Surgery, Kirkham, 2ISSA 20–30 years. Increased levels of cadmium are observed in the working Medical Centre and 3Rheumatology Department, Lancashire Care class and those living in industrial areas independent of their smoking NHS Foundation Trust, Preston, UK history. Cadmium levels in scalp hair samples are raised in RA men independent of the smoking history. Cadmium has been observed in RA Background: Bisphosphonates originally started off as water softening SF and is actively taken up by synovial fibroblasts. Chelating agents that agents in pipes and managed to reach a bestseller status as the complex with cadmium have been observed to improve the outcome in panacea for osteoporosis. Though relatively safe there have been seropositive RA (penicillamine and EDTA). Metallothionein binds to concerns about effects of long-term treatment including osteonecrosis cadmium and reduces the free radical activity of cadmium. of the jaw and atypical fractures secondary to adynamic bone formation. Metallothionein is greatly upregulated in the rheumatoid joint and a The National Osteoporosis Guideline Group (NOGG) advises that recent study using genome-wide DNA microarray analyses identified patients on bisphosphonates for more than 5 years undergo a risk metallothioneins to be strongly involved in the pathophysiology of RA. assessment after which a drug holiday may be considered. There is Nanoparticles have been observed to cause citrullination of bronchial ongoing discussion regarding the instigation and duration of this holiday. epithelial cells. Cadmium is one of the most important nanoparticles in Methods: We reviewed two general practices. Practice A had 10664 the context of environmental toxicity. Cigarette smoke condensate has registered patients and Practice B had 5958 patients. Patients with been observed to induce transcription of the heat shock protein system bisphosphonates on their repeat prescription were identified after a in the RA joint, cadmium alone has been observed to upregulate the VISION search in Practice A and an EMIS search in Practice B. Each heat shock system in a similar manner. Cadmium exposure independent patient’s record was reviewed to determine the length of bispho- of smoking is associated with peripheral vascular disease, coronary sphonate therapy and to check if they had been recalled for a risk artery disease, lung cancer and chronic obstructive pulmonary disease, assessment after 5 years of treatment. all of which are associated with seropositive RA. Results: Practice A: 130 patients were prescribed oral bispho- Conclusion: Exposure to cadmium appears to be a plausible sphonates on their repeat prescription, with 118 on alendronic acid explanation for the natural history of seropositive RA. and 12 on risedronate. Of these, 52 (40%) patients had been on Disclosure statement: The author has declared no conflict of interest. bisphosphonate therapy for more than 5 years. This group consisted of 41 females and 11 males. The age range was 57–91 years with a mean age of 76 years. None of the patients had been recalled for a risk E33. PREGNANCY OUTCOMES IN PATIENTS WITH assessment. Practice B: 52 patients were on oral bisphosphonates on RHEUMATOID ARTHRITIS WITH A HISTORY OF TREATMENT their repeat prescription, with 51 on alendronic acid and 1 on WITH RITUXIMAB: RESULTS FROM THE BSRBR-RA risedronate. Of these, 7 (32%) patients had been on bisphosphonate therapy for more than 5 years. This group consisted of six females and Lucy Birmingham1, Kath Watson1, Lianne Kearsley-Fleet1, one male. The age range was 52–82 years with a mean age of 66 Yvonne King1, Ursula Pattinson1, Deborah Symmons1 and years. None of the patients had been recalled for a risk assessment. Kimme L. Hyrich1 Conclusion: Within these two practices we found a considerable 1Arthritis Research UK Centre for Epidemiology, University of number of patients on bisphosphonate therapy for more than 5 years Manchester, Manchester, UK E-POSTER ABSTRACTS i185

years. In addition it is recommended that these vaccines are Background: Few data are available regarding effects of rituximab administrated prior to starting DMARD therapy, if possible. The prior to or during pregnancy. Guidelines suggest the drug should not proportion of patients with RA in the UK receiving these vaccinations, be administered within 12 months of conception. The objectives of this and the timing of vaccinations in relation to starting DMARD therapy, is descriptive analysis were to summarize the outcomes of pregnancy in not clear. The aim of this study was to measure the extent to which women with RA who received rituximab during/prior to pregnancy and patients with RA are vaccinated, and to determine the timing of the review adherence to current rituximab guidelines. vaccinations in relation to starting DMARD therapy. Methods: The British Society for Rheumatology Biologics Register for Methods: This was a retrospective cohort study using data from the Rheumatoid Arthritis systematically captures clinical information in Clinical Practice Research Datalink (CPRD), a large database of patients exposed to biologic therapy, including rituximab. Additional anonymized primary care data from general practitioners in the UK. data are collected from the rheumatology team once a report of a A cohort of patients who were diagnosed with RA and were prescribed pregnancy has been received including exposure to medications, DMARD therapy during follow-up (1 January 2000–31 December 2013) pregnancy outcome and complications. This analysis included all were identified. Patients needed to be aged 18 years or over and have patients with a reported pregnancy between 2001 and 2014 who had at least 12 months follow-up prior to entry. Vaccination coverage was been exposed to rituximab at any point prior to the end of pregnancy. time varying for both vaccines. The influenza season was estimated to Results: 22 pregnancies in 17 women (age range 20–41 years at start on 1 September. All patients were set to an unvaccinated status conception) were reported with exposure to rituximab (outcome known at the start of September, and were considered vaccinated until the in 19). 12 patients (63%) with known outcome had received their most end of August the following year if they were vaccinated before 31 recent rituximab dose within 12 months of conception. No women March. Vaccination for pneumonia was estimated to last for 5 years. received rituximab infusions during pregnancy (Table 1). Two women, Upon vaccination, pneumonia vaccination status changed to vacci- whose last rituximab infusion was >12 months prior to conception, had nated, at 5 years status reverted back to unvaccinated until further received other biologic drugs between their last rituximab infusion and vaccination. For both vaccines, patients were classified by the conception. Two stillbirths occurred, in the same patient, with rituximab following: having at least one vaccination and whether a vaccination doses at 9 and 18 months prior to conception. One patient, with was before starting DMARD therapy. exposure 1 month prior to conception and MTX exposure at conception, Results: 17 879 patients with RA identified who were treated with miscarried at 12 weeks. Three additional patients receiving MTX at DMARD therapy during follow-up. There were 14 158 (79%) patients conception with earlier rituximab exposure, had live births, including one who received at least one influenza vaccination. Of these, 7567 (54%) which was a twin pregnancy (one fetus was electively terminated due to patients were vaccinated prior to starting DMARD therapy. Only 8995 anencephaly). A further patient, who also received rituximab one month (50%) patients received at least one pneumonia vaccination. Of these prior to conception with SSZ, delivered a healthy term baby. The 3804 (42%) patients were vaccinated prior to starting DMARD therapy proportion of live births did not differ between women exposed more (Table 1). (71%) or less (75%) than 12 months prior to conception. There were no Conclusion: Uptake of vaccinations was greater for influenza than reports of premature births or congenital malformations. pneumonia in this group of patients with RA. Of those vaccinated, Conclusion: Although these data suggest that rituximab exposure in many received their vaccinations after starting DMARD therapy. the months prior to conception may not be associated with adverse Patients with RA on DMARD therapy should be encouraged to have pregnancy outcomes, caution must be urged when interpreting their influenza and pneumonia vaccinations, particularly prior to these data. There were low numbers of reported pregnancies with starting DMARD therapy, to prevent infection. most receiving combination DMARDs at conception. No data on Funding: This work was supported by Arthritis Research UK. neonatal lymphocyte counts/longer term childhood outcomes were Disclosure statement: The authors have declared no conflicts of captured. Further data are required before the manufacturer’s interest. suggestion of a 12 month infusion free window prior to conception can be changed. Disclosure statement: K.L.H. has received honoraria from Pfizer and E34 TABLE 1. Vaccination status in a cohort of patients with RA prescribed DMARD AbbVie. All other authors have declared no conflicts of interest. therapy (n ¼ 17 879) Flu vaccination, Pneumonia E33 TABLE 1. Summary of pregnancy outcomes* n (%) vaccination, n (%) Summary of pregnancy outcomes Value Received at least one vaccination 14158 (79.2) 8995 (50.3) during follow-up Patients, n 17 Of those vaccinated, vaccination 7567 (53.5) 3804 (42.3) Pregnancies, n 22 pre-DMARD therapy Known outcome, n 19 RTX exposure >12 months, n (%) 7 (37) RTX exposure <12 months, n (%) 12 (63) Receiving other medications at time MTX (4), SSZ (5), steroids (5), of (or prior to) conception, n HCQ (3), AZA (2), ciclosporin (2), ETN (1), E35. PREVALENCE OF POLYPHARMACY IN PATIENTS WITH a TCZ (1) RHEUMATOID ARTHRITIS AND ASSOCIATION WITH DISEASE Live births, n (%) 14 (74) CHARACTERISTICS Miscarriages/stillbirths, n/n 1/2 Termination, n 1 confirmed, 1 unconfirmed Maria Filkova1, Tim Mant2, Andrew Cope1 and James Galloway1 Termination due to anencephaly, n 1 1Academic Department of Rheumatology, King’s College London and Maternal complications, n (%) 3 (14%) including postpartum 2 haemorrhage (1), Quintiles Drug Research Unit at Guy’s Hospital, Quintiles, London, UK pre-eclampsia (1), pericardial effusion (1) Background: Polypharmacy is defined as prescribing of multiple Birth defects/neonatal deaths in live births, n 0 medications for an individual for complex/multiple conditions. a% represents percentage of pregnancies with known outcomes; ETN: etaner- Although appropriate polypharmacy is beneficial for quality of cept; RTX: rituximab; TCZ: tocilizumab. life and life expectancy, most trials have focused on patients with limited comorbidity and consequently the evidence base for poly- pharmacy across diseases is limited. Polypharmacy increases the risk of drug interactions and adverse events, including increased rates of E34. VACCINATION UPTAKE IN PATIENTS WITH hospitalization. In addition, polypharmacy associates with poorer RHEUMATOID ARTHRITIS TREATED WITH DISEASE- adherence to treatment and increased drug expense. Our objective MODIFYING ANTI-RHEUMATIC DRUG THERAPY: A was to analyse the prevalence of polypharmacy and relationship with RETROSPECTIVE COHORT STUDY USING UK PRIMARY disease characteristics in patients with RA. CARE ELECTRONIC MEDICAL RECORDS Methods: This cross-sectional analysis was performed on routinely captured clinical data on RA patients fulfilling 1987 ACR criteria visiting Ruth Costello1, Kevin Winthrop2, Stephen R. Pye1 and the outpatient clinic of an inner-city London hospital using the William Dixon1 electronic medical record. Statistical analysis included Chi-squared, 1Centre for Musculoskeletal Research, University of Manchester, Mann–Whitney and Spearman correlation coefficient. Manchester, UK and 2Department of Public Health and Preventative Results: The study included 1101 patients with RA with mean DAS for Medicine, Oregon Health and Science University, Portland, OR, USA 28 joints (DAS28) 3.64 (S.D. 1.61), HAQ 1.34 (S.D. 0.93) and disease duration 10.42 (S.D. 9.93) years of whom 75% were seropositive. Background: The guidelines for the management of RA recommend The mean age was 61.34 years (S.D. 16.00) and 79% were an annual influenza vaccine and a pneumonia vaccination every 5 females. Overall the mean number of prescribed medications was i186 E-POSTER ABSTRACTS

5.22 (S.D. 3.30). The number of medications significantly correlated E36 TABLE 1. DAS and disease status by duration of diagnosis with DAS28 ( ¼ 0.26, P < 0.001), HAQ ( ¼ 0.45, P < 0.001), age Expected Actual Month DAS28-ESR, Cases in Cases in ( ¼ 0.27, P < 0.001) and disease duration ( ¼ 0.14, P < 0.001). 31% no. of visits data mean (S.D.) remission, % low disease of patients below 65 years were on six or more medications, compared points activity, % with 52% of patients above 65. 16% of patients above 65 were on 10 94 85 0 5.2 (1.1) 0 4.7 or more medications. Women were on significantly higher numbers of 91 74 1 3.7 (1.5) 25.7 37.8 medications compared with males (5.3 3.22 vs 4.9 3.6, P ¼ 0.01). 90 58 2 3.1 (1.2) 39.7 55.2 79% of patients were on DMARDs, 22% on biologics (5.72% on 89 73 3 2.8 (1.2 47.9 69.9 monotherapy). Out of all patients on DMARDs, 45% were on 89 59 4 2.5 (1.0) 66.1 81.4 monotherapy, 26% were on dual and 7% on triple combination 85 58 5 2.7 (1.1) 56.9 82.8 84 70 6 2.7 (1.3) 58.6 75.7 DMARDs therapy, 15.80% were on combination with biologics and 74 65 9 2.5 (1.4) 58.5 78.5 11.17% were on combination with CSs. After excluding immunomo- 69 58 12 2.4 (1.2) 62.1 75.9 dulators for RA treatment, the most common prescribed therapies included treatment for cardiovascular diseases (38%, calcium channel DAS28: DAS for 28 joints. blockers 25%, diuretics 24%, a/b blockers 17%, sartans 13%, angiotensin-converting-enzyme inhibiters 6%, others 15%), opioid- based analgesia (34%) and non-steroid anti-inflammatories (32%). E37. DOES BODY MASS INDEX IMPACT LONG-TERM Conclusion: Broad-spectrum polypharmacy is common in patients RETENTION WITH ABATACEPT IN PATIENTS WITH with RA and is more frequently observed in women, patients RHEUMATOID ARTHRITIS WHO HAVE RECEIVED AT LEAST with higher disease activity, higher levels of functional impairment ONE PRIOR BIOLOGIC AGENT? 2-YEAR RESULTS FROM A and longer disease duration. None of these observations is unex- REAL-WORLD, INTERNATIONAL, PROSPECTIVE STUDY pected; however, the absolute numbers of patients receiving poly- 1 2 3 pharmacy is high, especially in the elderly. There is growing evidence Hubert Nu¨ ßlein , Rieke Alten , Mauro Galeazzi , Hanns- Martin Lorenz4, Michael T. Nurmohamed5, William G. Bensen6, Gerd that patients receiving six or more drugs are at a significantly increased 7 8 9 10 risk of adverse health outcomes. In the context of RA, where we R. Burmester , Hans-Hartmut Peter , Peter Peichl , Karel Pavelka , Melanie Chartier11, Coralie Poncet12, Christiane Rauch13 and routinely advocate combination therapy, more research is needed to 14 evaluate the impact of polypharmacy in our patients. Manuela Le Bars 1Radiology, Internistische Schwerpunktpraxis, Nu¨ rnberg, Disclosure statement: M.F. received an ARUK EATC grant to support 2 this study. The other authors have declared no conflicts of interest. Rheumatology, Schlosspark-Klinik University Medicine, Berlin, Germany, 3Rheumatology, University of Siena, Siena, Italy, 4Rheumatology, University Hospital, Heidelberg, Germany, 5Rheumatology, VU University Medical Centre/Jan van Breeman E36. TIGHT CONTROL OF RHEUMATOID ARTHRITIS IN A Research Institute, Amsterdam, The Netherlands, 6Department of REAL LIFE CLINIC Medicine, St Joseph’s Hospital and McMaster University, Hamilton, ON, Chetan Mukhtyar1 Canada, 7Rheumatology and Immunology, Charite´ —University 1Rheumatology Department, Norfolk and Norwich University Medicine Berlin, Berlin, 8Centre of Chronic Immunodeficiency, Hospital, Norwich, UK University of Freiburg, Freiburg, Germany, 9Internal Medicine, Evangelisches Krankenhaus, Vienna, Austria, 10Institute of Background: Tight control of early RA with standard DMARDs is Rheumatology and Clinic of Rheumatology, Charles University, Prague, highly effective. Current recommendations instruct treating RA to Czech Republic, 11Real World Research Department, Chiltern target remission. I set up an early RA clinic in January 2011 with a International, Neuilly, 12Biostatistics, Docs International, Se` vres, France, structured escalation plan. I present the experience of the first 12 13Medical Affairs Immunoscience, Bristol-Myers Squibb, Munich, months of follow-up of my cohort. Germany and 14Medical Affairs, Bristol-Myers Squibb, Rueil-Malmaison, Methods: All patients with a new diagnosis of RA as defined by ACR/ France EULAR 2010 criteria are entered into a dedicated clinic. Cases are followed monthly for 6 months, and then 3-monthly until 24 months. A Background: In RA, reduced efficacy with anti-TNF therapy and dose standard escalation protocol is followed starting with 15 mg/week MTX escalation have been reported for obese patients compared with non- in most cases as first choice. DMARDs are added every month as obese patients. Clinical trials have shown that BMI does not affect necessary. Joint injections or intramuscular Depo-Medrone injections abatacept (ABA) efficacy or pharmacodynamics and real-world data are offered to all patients if they are not in remission, for the first 6 show that short-term ABA retention, dosing and treatment outcomes months. Inflammatory markers are checked within 2 weeks of clinical are unaffected by BMI. We assessed the impact of BMI on the long- assessment. Cases were diagnosed between January 2011 and term retention of patients using i.v. ABA who had previously failed 1 November 2014. Data were analysed for number of visits, recording biologic in clinical practice across Europe and Canada. of DAS for 28 joints (DAS28)-ESR, number of cases achieving DAS28 Methods: ACTION was a 2-year, non-interventional, international, remission and low disease activity state, amount of CS and biologic multicentre, cohort study that evaluated the retention and effectiveness use. of i.v. ABA in adults with moderate-to-severe RA. Patients who received Results: 94 patients met the definition of RA during this period (32 1 prior biologic and enrolled in countries with sufficient patient male: 62 female). The mean age at diagnosis was 61.1 (S.D. 14.6). The numbers to explore between-country effects were included in this median RA classification score was 7 (25th percentile 7, 75th analysis. Patients were stratified by their baseline BMI. Crude 2-year percentile 8). 18/94 were seronegative for RF and anti-CCP antibodies. retention rate was estimated using the Kaplan-Meier method. The effect 59/94 had either one of the antibodies in a titre >3 upper limit of of BMI was analysed through a multivariate Cox proportional hazard normal. The median delay in reaching 15 mg/week MTX was 0 days model clustered for site effects with conditional imputation of missing (25th percentile 0, 75th percentile 3.5). Two cases did not start/reach data for covariates. Hazard ratios and corresponding 95% CI were MTX 15 mg. HCQ was used in 66 cases, LEF in 30 cases and SSZ in 9 adjusted for sociodemographic variables, disease characteristics, cases. The expected and actual number of visits is as in Table 1. comorbidities at initiation and treatment characteristics. Patients were Appropriate data collection was carried out in 600 visits in 12 months considered adherent to ABA if the ratio of the number of infusions follow-up. 80 further visits did not have ESR (29 of those had CRP). received to the number expected was between 80% and 120%. The DAS28-ESR values for each month are in Table 1. 79/94 cases Results: 1009/1131 (89.2%) evaluable patients had received 1prior have achieved remission at least once. The median time to remission is biologic; 995 were included in the analysis. Patients with higher BMI had 3 months (25th percentile 2, 75th percentile 4). At 12 months 62% shorter disease duration, more severe disease (assessed by tender joint were in remission, and 75% had low disease activity. 3.9 injections/ count, DAS for 28 joints and HAQ-DI), were more likely to have patient of i.m./IA CSs were used in the first 6 months. Four patients comorbidities, but were less likely to be RF or anti-CCP antibody positive. qualified for biologic therapy in the first 12 months. Crude retention rates and adjusted hazard ratio are shown in Table 1. Conclusion: Tight control of RA comparable to clinical trial setting is Similar proportions of patients were considered adherent to ABA achievable in routine clinical practice by disciplined clinical pathways. therapy in all BMI groups as follows: BMI <25 kg/m2, 82.8%; BMI 25 to At a subjective level, it is hard work to ensure to ensure strict rigour, <30 kg/m2,79.5%;BMI30to<35 kg/m2,85.0%andBMI35 kg/m2, but this effort is rewarded by excellent patient outcomes. 84.1%. Disclosure statement: C.M. has received research grants from the Conclusion: In this analysis of the real-world ACTION study, BMI did EULAR. not impact long-term retention of i.v. abatacept in patients who had E-POSTER ABSTRACTS i187

previously received 1 biologic, when adjusted on differences in patients (9/13) expressed a preference for DMARD minimization. disease severity and comorbidities between BMI classes. Increased However, others were strongly against DMARD cessation; patients in BMI was not associated with an increased number of infusions, this group had previous personal or family experience of severe indicating that i.v. abatacept can be an effective treatment option deforming arthritis, or significant vulnerability to any loss of physical irrespective of BMI, without need for dose adjustment. This study was function owing to the demands of employment or dependent others. supported by Bristol-Myers Squibb. Conclusion: Patients considered DMARD minimization in the context Disclosure statement: H.N. has received consulting fees from BMS, of their normal life. Many patients viewed DMARD withdrawal as an Abbott, Chugai, UCB, Essex, Wyeth, Pfizer, MSD, Novartis and Roche. opportunity to restore a normal lifestyle through the avoidance of R.A. has received consulting fees and research grants from BMS. H.M.L. important disruptions including drug administration, risk of side effects has received consulting fees from BMS. M.T.N. has received consulting and blood monitoring. Nevertheless, for other patients DMARD fees from BMS and Janssen; has served on speakers’ bureaus on behalf withdrawal threatened a normal lifestyle—risking loss of physical of Roche, AbbVie, Pfizer, and UCB; and has received research grants function that jeopardized their employment or caring role, or risking from Roche, AbbVie, Pfizer, MSD, UCB and BMS. W.G.B. has received progression they had witnessed in others. All patients expressed a consulting fees from Abbott, Amgen, BMS, Janssen, Merck, Lilly, clear preference either for or against DMARD withdrawal, highlighting Novartis, Pfizer, Proctor and Gamble, Roche, Sanofi-Aventis, Schering, the absolute importance of patient preference in this shared decision- Takeda, UCB, Warner Chilcott, and Wyeth; has served on speakers’ making process. This study provides unique insights that will allow bureaus on behalf of Abbott, Amgen, BMS, Janssen, Merck, Lilly, clinicians to address patients’ concerns more effectively when Novartis, Pfizer, Proctor and Gamble, Roche, Sanofi-Aventis, Schering, discussing DMARD withdrawal in the context of RA remission. Takeda, UCB, Warner Chilcott, Wyeth; and has received research grants Disclosure statement: The authors have declared no conflicts of from Abbott, Amgen, BMS, Janssen, Merck, Lilly, Novartis, Pfizer, interest. Proctor and Gamble, Roche, Sanofi-Aventis, Schering, Takeda, UCB, Warner Chilcott and Wyeth. G.R.B. has received consulting fees from AbbVie, BMS, MSD, Medimmune, Novartis, Pfizer, Roche, Sandoz, and E39. ABSTRACT WITHDRAWN UCB; has served on speakers’ bureaus on behalf of AbbVie, BMS, MSD, Pfizer, Roche, Sandoz, and UCB; and has received research grants from AbbVie, Pfizer, Roche and UCB. K.P. has received consulting fees from MSD, AbbVie, Pfizer, UCB, Roche, Amgen, Menarini, and BMS. M.C. has E40. ABSTRACT WITHDRAWN received consulting fees from BMS. C.P.: consultancy for BMS; BMS. C.R. is an employee of BMS. M.L.B. is a stockholder and employee of BMS. All other authors have declared no conflicts of interest. E41. INVESTIGATION OF GENETIC VARIANTS IN

E37 TABLE 1. Crude retention rates and adjusted hazard ratios PREDICTING RESPONSE TO BIOLOGIC DRUGS USED TO TREAT RHEUMATOID ARTHRITIS BMI class, kg/m2 n (%) Crude retention Adjusted 95% P-value rate, % (95% CI) hazard CI Chin Ming Hao1, Darren Plant2, John Isaacs3, Kimme L. Hyrich4, ratio Ann Morgan5, Gerry Wilson6 and Anne Barton7 Underweight/ 359 (36.1) 53.8 (48.3, 59.0) 1 1School of Medicine, 2NIHR Manchester Musculoskeletal Biomedical normal, <25 Research Unit, University of Manchester, Manchester, 3Institute of Overweight, 324 (32.5) 57.4 (51.5, 62.8) 0.90 0.72, 1.13 0.365 Cellular Medicine, University of Newcastle upon Tyne, Newcastle, 25 to <30 4Arthritis Research UK Centre for Epidemiology, University of Obese class I, 168 (16.9) 50.5 (42.4, 58.1) 0.96 0.71, 1.31 0.815 5 30 to <35 Manchester, Manchester, Leeds Institute of Rheumatic and 6 Obese class II/III, 85 (8.5) 53.2 (41.3, 63.7) 0.86 0.58, 1.26 0.437 Musculoskeletal Medicine, University of Leeds, Leeds, Academic 35 Unit of Rheumatology, University of Sheffield, Sheffield and 7Arthritis Research UK Centre for Genetics and Genomics, University of Manchester, Manchester, UK E38. RESTORING OR THREATENING A NORMAL LIFE: WITHDRAWING MEDICATION FROM PATIENTS WITH Background: Etanercept, a soluble tumour necrosis factor (TNF) RHEUMATOID ARTHRITIS IN REMISSION receptor fusion protein, is a biologic drug that can be used to treat RA, which is resistant to standard disease-modifying therapies. However, Kenneth Baker1, John Isaacs1 and Ben Thompson1 30% of patients fail to respond and given the high cost of treatment 1Musculoskeletal Research Group, NIHR Newcastle Biomedical and risk of side effects, there is a need to identify predictive factors of Research Centre, Newcastle University and Newcastle upon Tyne anti-TNF treatment response. Recently, a genome-wide association Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK study (GWAS) identified a single nucleotide polymorphism (SNP), rs6427528, mapping to the CD84 gene locus to be associated with Background: A significant proportion of patients with RA can achieve etanercept treatment response (n ¼ 733; P ¼ 8 10–8). Our current remission using modern DMARD treatment. Current guidelines from study aimed to test association of the same SNP in an independent UK EULAR suggest DMARD minimization in RA remission; however, little RA etanercept-treated population. is known regarding patients’ concerns and response to this practice. In Methods: DAS for 28 joints (DAS28) was computed in 247 British RA this qualitative research study, we aimed to explore the issues patients at baseline and at 3/6 months after initiation of etanercept surrounding DMARD withdrawal from a patient perspective. treatment. DNA samples were genotyped using either Illumina or Methods: Patients with RA judged to be in remission by their referring Affymetrix genotyping arrays. Following quality control of the genotyp- rheumatology clinician were recruited from consecutive rheumatology ing data, the SNP rs6427528 was tested for association with treatment outpatient clinic attendances and invited to discuss their views of DMARD response, defined as the change in DAS28 score between pre- therapy within a semi-structured interview. Purposive sampling was used treatment and 3/6 months post treatment (ÁDAS28), using linear in later recruitment to select patients receiving biologic therapy not regression. Linear regression analysis was carried out using PLINK represented in the initial cohort. Interviews were conducted by the same (version 1.07) software and statistical power for the current study was researcher (K.B.) and focused on three topics: benefits of DMARDs, calculated using the software Quanto. A meta-analysis was performed disadvantages including drug side effects, and opinion regarding using the METAL software tool, combining the current data with the potential DMARD withdrawal. Interview recordings were transcribed original GWAS to determine the association of the CD84 SNP with verbatim using conversation notation and reviewed to identify emerging etanercept treatment response. themes, which were explored further by standard qualitative techniques Results: Our study had 68% power to detect the same effect size as including constant comparison, deviant case analysis and memoing. The reported in the original GWAS at the 5% significance threshold resulting analytical framework was reviewed with reference to the (P ¼ 0.05). No evidence for association between the SNP rs6427528 transcripts and agreed between researchers. and etanercept treatment response (ÁDAS28) was detected in our Results: Saturation of themes was reached after 13 patient interviews [8 patient group (P ¼ 0.18; Table 1). However, the meta-analysis revealed female, median (IQR) age 65 (61–73) years and 10 (3–13) years since RA a strong association between the SNP and etanercept treatment diagnosis]. Patients identified a range of advantages of DMARD therapy response (ÁDAS28), albeit with less significance than the original including prevention of physical symptoms of RA (pain, swelling and study (P ¼ 1.06 107). stiffness), maintenance of mobility and prevention of future deterioration Conclusion: In a replication study carried out within the UK RA in physical function. In the majority of cases these benefits were framed population, we found no association between the CD84 SNP within the context of everyday activities and living a normal life. rs6427528 and etanercept treatment response. More replication Disadvantages of DMARDs were framed as disruptions to their normal studies will have to be carried out in larger sample sizes to confirm if lifestyle, such as medication side effects and blood monitoring. Most this association is indeed a genuine one. i188 E-POSTER ABSTRACTS

Disclosure statement: The authors have declared no conflicts of E42 TABLE 1. Safety data from ACT-UP (6 months) interest. TCZ Mono TCZ Combo All patients (n ¼ 352) (n ¼ 609) (n ¼ 961) AEs, n (%) 185 (52.6) 324 (53.2) 509 (53.0) E41 TABLE 1. Results of SNP rs6427528 with etanercept treatment response in Rate per 100 py 193 205 201 current and previous studies AEs by SOCa Current study Cui et al. Meta- Infections and infestations 56 (15.9) 132 (21.7) 188 (19.6) (n ¼ 247) study analysis Investigations 38 (10.8) 71 (11.7) 109 (11.3) (n ¼ 733) Musculoskeletal and connective 33 (9.4) 52 (8.5) 85 (8.8) tissue disorders Gastrointestinal disorders 29 (8.2) 49 (8.0) 78 (8.1) SNP Ref- Chromosome b (95% CI) P- b P-value P-value Skin and s.c. tissue disorders 28 (8.0) 44 (7.2) 72 (7.5) allele value General disorders and administration 22 (6.3) 34 (5.6) 56 (5.8) 8 7 rs6427528 A 1q23 0.29 (–0.13, 0.18 0.71 8 10 1.06 10 site conditions 0.71) Blood and lymphatic system disorders 20 (5.7) 44 (7.2) 64 (6.7) b: regression coefficient; Ref-allele: reference allele for the association test; SNP: Nervous system disorders 18 (5.1) 32 (5.3) 50 (5.2) single nucleotide polymorphism. Metabolism and nutrition disorders 18 (5.1) 23 (3.8) 41 (4.3) SAEs, n (%) 34 (9.7) 49 (8.0) 83 (8.6) Rate per 100 py 23 19 21 Infection SAEs, n (%) 6 (1.7) 15 (2.5) 21 (2.2) E42. PATTERNS OF TOCILIZUMAB USE AND SAFETY IN Total AEs leading to withdrawal, n (%) 32 (9.1) 42 (6.9) 74 (7.7) Rate per 100 py) 21 14 16 PATIENTS WITH RHEUMATOID ARTHRITIS: INTERIM AEs leading to withdrawal by SOCb RESULTS FROM ACT-UP: A MULTINATIONAL Skin and s.c. tissue disorders, n (%) 6 (1.7) 5 (0.8) 11 (1.1) OBSERVATIONAL STUDY Infections and infestations, n (%) 5 (1.4) 6 (1.0) 11 (1.1) 1 2 3 4 Gastrointestinal disorders, n (%) 4 (1.1) 1 (0.2) 5 (0.5) Boulos Haraoui , Gustavo Casado , Elke Theander , Laszlo Czirja´ k , Cardiac disorders, n (%) 4 (1.1) — 4 (0.4) 5 6 7 Andrew Taylor , Peter Button , Lykke Hinsch Gylvin and Blood and lymphatic system 3 (0.9) 7 (1.1) 10 (1.0) Roberto Caporali8 disorders, n (%) 1Rheumatology Department, Institut de Rhumatologie, Montreal, QC, 2 Rate per 100 py is based on total number of events during TCZ exposure, Canada, Me´ dico Reumato´ logo, Hospital Militar Central, Buenos determined for each patient as date of last TCZ dose date of first TCZ dose þ 28 3 Aires, Argentina, Department of Rheumatology, Ska˚ ne University days. aReported in 5% of patients in a treatment group. bReported in 1% of Hospital Malmo¨ , Lund University, Sweden, 4University of Pe´ cs, patients in a treatment group. Combo: in combination with DMARDs; Mono: Medical Centre, Pe´ cs, Hungary, 5Rheumatology Department, Royal monotherapy; py: patient-years; SAEs: serious AEs; SOC: system organ class; Perth Hospital, Perth, 6Medical Department, Roche Products Pty TCZ: tocilizumab. Limited, Dee Why, Australia, 7Medical Department, F Hoffmann-La Roche, Basel, Switzerland and 8University of Pavia, IRCCS S. Matteo Foundation, Pavia, Italy E43. AN EXPLORATION OF STRATEGIES TO ENHANCE PHYSICAL ACTIVITY IN PEOPLE WITH RHEUMATOID Background: Tocilizumab (TCZ) is indicated for RA patients with ARTHRITIS inadequate responses to DMARDs, either as monotherapy (Mono) or in combination with DMARDs (Combo). ACT-UP pools data from several Rachel Thomas1, Sarah Hewlett2, Caroline Swales3 and international, observational, post-marketing studies of i.v. TCZ. Interim Fiona Cramp1 observations of patterns of TCZ-use in RA patients, adherence to label 1Allied Health Professions, 2Nursing and Midwifery and 3Patient recommendations and safety are reported. Research Partner, University of the West of England, Bristol, UK Methods: Adult patients with moderate-to-severe RA who started TCZ in routine practice were observed in clinical practice for 6 months. Background: People with RA were traditionally advised to avoid There were no specified dosing regimens (concomitant RA treatments exercise as it was thought to exacerbate joint damage. However, permitted) and no interventional procedures, clinic visits, or laboratory there is now strong evidence that regular physical activity (PA) is analyses outside routine practice. safe and beneficial to those with RA. Despite this, the majority of Results: Data are reported for 961 patients receiving TCZ [352 (37%) people with RA are less active than the general population. They are initiated as Mono and 609 (63%) as Combo]. 94% and 95% of Mono also at greater risk of cardiovascular problems and limited function and Combo patients, respectively, started TCZ at 8 mg/kg, and 93% which are exacerbated by inactivity. Effective methods to support and 94% of patients, respectively, taking TCZ at 6 months received long-term engagement with PA need to be identified for those with 8 mg/kg. TCZ dose changes occurred in 34 (10%) Mono patients RA. The primary aim of this project was to explore the strategies (7 increased, 11 decreased, 16 increased and decreased) and 68 employed by people with RA who are successfully engaging with (11%) Combo patients (13 increased, 20 decreased, 35 increased and regular PA. decreased). Reasons for dose changes were: adverse events (AEs; 4% Methods: A purposive sample of physically active people with RA Mono; 5% Combo) and lack of efficacy (2% Mono; 1% Combo). participated in semi-structured interviews. In-depth perspectives of Median MTX dose for Combo patients was 15.0 mg/week. 63 patients the participant’s attitudes, behaviours and experiences surrounding changed MTX dose (median dose change 5.0 mg/week). 28 (8%) of PA as well as the strategies that they use to remain active were TCZ mono patients added a DMARD during the study. Corticosteroids explored. Interviews were analysed thematically. were used by 57% of Mono and 70% of Combo patients (median Results: Twelve female and three male participants were recruited prednisone-equivalent dose (at baseline) 7.5 and 5.0 mg/day, respec- (mean age 56 years, range 29–80; mean disease duration 13 years, tively). At 6 months, 72% of Mono and 84% of Combo patients were range 10 months to 46 years). Analysis revealed eight constructs still receiving TCZ. 100 (10%) patients discontinued TCZ in the first which were clustered into three themes reflecting the interlinking 3 months; 94 (10%) in the next 3 months (reasons: lack of efficacy factors affecting participant’s engagement with PA. Themes incor- (11% Mono; 27% Combo), AEs (27% Mono; 29% Combo), other porated an individual’s symptoms, feelings and role, their manage- reasons (62% Mono; 44% Combo). AEs occurred in 53% of patients ment (medical and self) and the type of PA they participated in (Table 1). Infections were less common in Mono patients. No including whether there were any barriers or facilitators to activity. gastrointestinal perforations were reported. Activities with a social element, dog walking, cycling or walking as a Conclusion: In clinical practice, 37% of patients started TCZ as mode of transport, yoga and hydrotherapy were popular types of monotherapy and most patients continued with TCZ treatment (Mono activity. Many participants reported a long history of being and Combo) 6 months after initiation. TCZ was well tolerated in both physically active prior to diagnosis and most had good support groups. networks. All participants recognized PA played a key role in the Disclosure statement: B.H. has acted as a consultant for AbbVie, management of their RA and all recognized benefits from engaging Amgen, BMS, Janssen, Pfizer, Roche and UCB; and has received in PA and were able to overcome barriers such as pain, loss of research grants from AbbVie, Amgen, BMS, Janssen, Roche, UCB. G.C. confidence or motivation. has acted as a consultant for Abbott, Pfizer, Janssen, Roche and GSK. Conclusion: Findings indicate that all participants had high levels of E.T. has acted as a consultant for Roche. L.C. has acted as a consultant exercise self-efficacy and strong beliefs that their functional ability for AbbVie, Pfizer, Roche, UCB and MSD. A.T. has acted as a consultant would decline without regular physical activity. Participation in physical for AbbVie, Roche, Celgene, Janssen, BMS and UCB; and has served activity promoted a sense of belonging to and contribution to society. on speakers’ bureaus on behalf of AbbVie, Roche, Janssen, BMS and These findings are comparable with a recent similar study. A UCB. P.B. is an employee of Roche. L.H.G. is an employee of Roche. subsequent phase of this study will aim to determine whether the R.C. has acted as a consultant for AbbVie, BMS, Roche, UCB and MSD. identified strategies are acceptable to a wider group of people with RA. E-POSTER ABSTRACTS i189

The overall findings may help to inform the development of future Methods: This study has an exploratory qualitative design using focus exercise interventions for people with RA. If people with RA can groups and semi-structured interviews. Two focus groups took place: engage with appropriate levels of PA there is the potential for involving patients with RA and involving carers of patients with RA. enhancing longer term health and function. Seven semi-structured interviews were conducted face-to-face or via Disclosure statement: The authors have declared no conflicts of the telephone (with the exception of patients whose first language is interest. not English who were all interviewed in person with the assistance of a translator). Audio recordings of focus groups and interviews were transcribed and analysed using Framework Analysis. Five main themes E44. DOES STEROID TREATMENT REDUCE BONE MINERAL were identified including the nature of RA, expectations of intensive DENSITY IN PATIENTS WITH RHEUMATOID ARTHRITIS? management, acceptability of intensive management, continuity of

1 2 2 care and patient information. Kristen Davies , Alex Oldroyd and Marwan Bukhari Results: Fourteen participants were recruited (9 patients, 5 carers). 1Faculty of Health and Medicine, Lancaster Medical School and 2 Expectations of intensive management included both psychosocial Rheumatology, University Hospitals of Morecambe Bay NHS Trust, and physical factors; the most commonly cited included increased Lancaster, UK independence and reduced pain, respectively. Increased clinic appointments were regarded as advantageous to most participants Background: Treatment of RA frequently utilizes steroid to control the as this corresponded to feeling more closely monitored. The inflammation caused by the disease. Both RA and steroids have acceptability of intensive treatment was influenced by patients’ detrimental effects on BMD. Van Staa previously suggested that previous care and side effects experienced. For carers, how patients steroids in RA worsen bone health. However, it is not known whether were currently responding to their treatment was a key factor. this affects cortical bone (hip) or trabecular bone (spine). Continuity of care was important for patients and carers, but Methods: To investigate the impact of steroid use on RA patients particularly so for those who had developed a trusting relationship independently on the BMD in the spine and femoral neck in RA and confidence in their specialist nurse and/or consultant patients referred for BMD estimation using DXA. All patients with RA rheumatologist. attending for BMD estimation using DXA in a district hospital Conclusion: Few studies have explored patients’ and carers’ views scanner between 2004 and 2011 were used. Within that cohort, two about intensive treatment strategies. These preliminary findings groups were identified: those who currently use steroids and those suggest that the acceptability of intensive treatment to patients and who were not using steroids at the time of DXA. The BMD in the carers is largely positive, although influenced by several factors. lumbar spine and femoral neck was compared between the groups. Negative comments regarding intensive treatment arose from patients’ The difference in BMD was ascertained using Student’s t-test. concerns about increased medication, especially in the context of prior Logistic models were fitted examining the predictors of bone loss in adverse effects. each group. Disclosure statement: L.P. has received research grants from Results: 810 patients with RA were referred in the study period. Mean TITRATE programme funded by the NIHR; and receives salary funding age was 66.5 years (S.D. 11.6). 637 (78.6%) were female. 188 (23%) by the NIHR. All other authors have declared no conflicts of interest. were on steroids at the time of DXA (mean age 65.2 years, S.D. 11.96) and 622 (77%) were not on steroids at the time of DXA (mean age 66.9 years, S.D. 11.5). For both groups, BMD was lower in the femoral E46. DIAGNOSIS AND EARLY MANAGEMENT OF neck than in the lumbar spine: current steroid use 0.83 g/cm2 (95% CI RHEUMATOID ARTHRITIS: EXPERIENCE OF A DEDICATED 0.81, 0.85) vs 1.07 g/cm2 (95% CI 1.05, 1.10), no steroid use 0.83 g/ NURSE-LED SERVICE cm2 (95% CI 0.82, 0.85) vs 1.08 g/cm2 (95% CI 1.07, 1.10). Comparing Paul Arkell1, Cath Thwaites1, Chantel-Lea Grocott1 and the two groups, the mean difference in BMD was not significantly 1 2 Jon Packham different in the lumbar spine (0.01 g/cm 95% CI 0.02, 0.04) or the 1 femoral neck (0.006 g/cm2 95% CI 0.02, 0.03). Logistic regression Rheumatology, Haywood Rheumatology Centre, Burslem, UK yielded an odds ratio of 0.496 (95% CI 0.124, 1.99, P ¼ 0.323) and 0.670 (95% CI 0.276, 1.63, P ¼ 0.378) when comparing steroid use Background: RA is a common autoimmune condition causing with BMD in the femoral neck and the lumbar spine, respectively. inflammatory polyarthritis, joint erosion and deformity. NICE guidance Steroid users suffered 39 fractures (26%) compared with 141 (29%) supports the notion of prompt and aggressive medical management with no steroid use. aiming for early disease control using glucocorticoids and combination Conclusion: In this group of RA patients referred for DXA, BMD is DMARDs, and a phase of intensive monitoring with monthly disease lower in the femoral neck than the lumbar spine. Steroid use in RA was activity assessment. At the Haywood Rheumatology Centre patients not found to be associated with a lower BMD in the femoral neck or the with newly diagnosed RA should be referred into the Nurse-Led lumbar spine of these patients. Although there are limitations to this Disease Management and Education Service for coordination of care study, including the lack of knowledge of the dosage and duration of during their first 16 weeks. Assessment for i.m. steroid injection and/or the steroid therapy, it would appear that steroids do not independently DMARD escalation is made every month according to a locally agreed increase bone loss in the femoral neck or lumbar spine. protocol. This audit of RA diagnosis and early management against Disclosure statement: The authors have declared no conflicts of NICE guidance also assessed patient outcomes in the year following interest. diagnosis, comparing those seen by the nurse-led service with those receiving only routine follow-up. Methods: All new patients during January–April 2012 subsequently E45. A QUALITATIVE STUDY TO EXPLORE PATIENTS’ AND receiving DMARDs for diagnosis of RA were included. Data were CARERS’ VIEWS AND EXPECTATIONS ABOUT INTENSIVE collected by retrospective case note review looking for demographic, TREATMENT FOR INTERMEDIATE RHEUMATOID ARTHRITIS disease-related, diagnostic, patient-flow and treatment variables. Analysis was with descriptive statistics and Student t-tests and Louise Prothero1, Sofia Georgopoulou1, Ailsa Bosworth2, Mann–Whitney U tests for associations in parametric/non-parametric Ruth Williams1, James Galloway1 and Heidi Lempp1 data. 1Academic Department of Rheumatology, King’s College London, Results: Forty-two new RA diagnoses were made over a 4-month London and 2National Rheumatoid Arthritis Society, National sample period, representing 8% of all new patients and 43% of all Rheumatoid Arthritis Society, Maidenhead, UK patients going on to receive DMARDs. Estimated local RA incidence was 0.25 per 1000 patients per year. Patients were 57% female, 93% Background: There have been significant advances in the manage- white British and had median age of 61 years. Median symptom ment of RA in recent decades with the introduction of intensive duration at presentation was 7 months. 64% and 74% of cases were treatment strategies using a combination of DMARDs and in some positive for RF and ACPA, respectively, and musculoskeletal US cases the addition of biologics (e.g. anti-TNF drugs). Intensive scanning was used in 64% of diagnoses. 72% were referred into the treatment regimens require frequent hospital visits and a high nurse-led clinic, and these individuals were more likely to have shorter number of medications, however, they have been shown to be symptom duration (P ¼ 0.058), initial assessment in early synovitis effective for highly active RA and patients generally accept the burden clinic rather than other clinics (P ¼ 0.083), and absence of tenosyno- of treatment. While intensive treatment is recommended for highly vitis on US scan (P ¼ 0.094). Patients seen in the nurse-led service active RA, there is no consensus pathway for patients with less active received more aggressive early management [higher rate of triple RA and the acceptability of intensive treatment strategies with less therapy (P ¼ 0.083) and number of IM depo steroids given (P ¼ 0.063)], severe disease is unknown. The purpose of this study is to understand and appeared to have better disease control [lower ESR as proportion the views and expectations of patients with RA receiving standard care of baseline at 1 (P ¼ 0.254), two (P ¼ 0.199), 3 (P ¼ 0.821), 6 (P ¼ 0.310) who have DAS between 3.2 and 5.1, and of carers of these patients, on and 12 (P ¼ 0.735) months after diagnosis]. There was also a higher intensive treatment. rate of advice-line contact in this group (P ¼ 0.005). i190 E-POSTER ABSTRACTS

Conclusion: This work provides a wealth of information about local Methods: 133 patients with RA [59.4% with early RA (<2 years)] were assessment, diagnosis and early management of RA. Findings are studied who within the 2-year period had been continuously receiving interesting and relevant to healthcare professionals and policy makers the same csDMARD. Mean age of patients was 49.6 0.58 years, and at other units, in particular those relating to improved outcomes among disease duration was 52.3 3.15 months. 84.2% patients were patients seen in our nurse-led service. The development of similar women, 63.2% were positive for RF and 75.2% for anti-CCP nurse-led services should improve the quality of care for early synovitis antibodies. Patients were treated with MTX (11.6 0.29 mg/week, patients. n ¼ 52), LEF (19.2 0.28 mg/day, n ¼ 25), SSZ (2 g/day, n ¼ 27) or Disclosure statement: The authors have declared no conflicts of combination csDMARDs (MTX, SSZ or LEF, HCQ, n ¼ 29). After 2 interest. years the response with DAS for 28 joints (DAS28), dynamics of DAS28 (ÁDAS28) and modified Sharp–van der Heijde score (ÁSHS) were evaluated. To determine independent predictors of X-Ray RA E47. ANTI-TNF-a MEDICATION DELIVERY: AN ARCHAIC progression, multifactorial linear regression analysis (MLRA) was used. HOLDOVER FROM A MORE PROFLIGATE TIME? Results: In patients, who have not responded to treatment with DAS28, Sean Kelly1, Christopher McAlpine1, Janice France1 and joint destruction was significantly greater [Á total SHS (TSS) 19.7 3.04] Sandeep Bawa1 vs patients, in which the response was moderate or good (7.0 1.0, 1Rheumatology, Gartnavel General University Hospital, Glasgow, UK P < 0.001) and vs patients with remission (4.26 1.07, P < 0.001). In patients with early RA correlation between ÁDAS28 and ÁTSS Background: Anti-TNF-a medication is expensive and part of the (r ¼ –0.49, P < 0.05) was stronger vs patients with late RA (r ¼ –0.26, expense is due to patients having medication delivered rather than P < 0.05). When LEF was prescribed, better correlation between collecting it. As a greater proportion of these patients are now working, ÁDAS28 and ÁTSS (r ¼ –0.43, P < 0.05) vs MTX (r ¼ –0.33, P < 0.05) are there better and more cost effective methods for dispensing these and combination csDMARDs (r ¼ –0.24, P < 0.05) was observed, while medications? for SS it was absent (r ¼þ0.20, P > 0.05). As a result of MLRA, expected Methods: A cohort of 100 patients attending the rheumatology after 2 years TSS ¼ 14.1 þ 2.1 (baseline ESS) þ 3.15 (centile level of anti- outpatient service at Gartnavel General Hospital, Glasgow, and CCP antibodies) þ 8.29 (if CRP elevated); for early RA: TSS ¼ 3.17 þ 0.87 prescribed anti-TNF-a for RA, PsA or AS, were assessed via (baseline TSS) þ 9.82 (if anti-CCP antibodies elevated); for late RA: questionnaire for both their ability and desire to collect medication TSS ¼ –3.44 þ 1.93 (baseline ESS) þ 3.81 (centile level of anti-CCP from a pharmacy; their satisfaction with their current delivery service; antibodies) þ 22.2 (if CRP elevated) þ 0.25 (ESR). and any problems with management of the medication. Conclusion: X-ray progression after 2 years of csDMARD treatment Results: Satisfaction with the three main delivery companies was high is generally associated with clinical response (dynamics of DAS28), (86–96%). 92% admitted they could collect medication, of whom 61% but this relationship is almost two-fold closer in patients with early (56/92) would prefer to collect. 8% stated they were not able to collect RA vs late. With LEF and MTX treatment there is a moderate medication; 20% preferred evening delivery, 12% weekend delivery; correlation between clinical and X-ray changes while for SSZ such 25% have been kept waiting for a delivery; 9% have been without connection is absent. The most important independent predictors of medication due to a failed delivery; 23% had disposed of medication X-ray RA progression is the presence and level of anti-CCP stored at home. 69% (24/35) of the working population would prefer to antibodies, baseline SHS and also level of CRP and ESR for collect their medication. In all age groups (under 30, 31–45, 46–60) late RA. except the over 60 s, patients preferred to collect their medication. Disclosure statement: The authors have declared no conflicts of Conclusion: The benefits of switching to a collection oriented service interest. are multi-fold. Delivery is paid for by the drug companies with this cost built into the medication price. Cutting out delivery costs would reduce the overall cost and savings could be passed onto the NHS. E49. HOW TO DELIVER GOOD OUTCOMES IN RHEUMATOID Additionally, the universal delivery service promotes wastage. ARTHRITIS AND MAXIMIZE CAPACITY WITH A Previous studies in this unit showed that in 2011, approximately MULTIDISCIPLINARY APPROACH £115 000 was wasted due to binned medication. In our patient cohort Rufus O’Reilly1, Ruth K. Slack1, Shweta S. Bhagat1, 23% had binned medication on at least one occasion. By switching to Vivek Rajagopal1 and David T. O’Reilly1 a collection service this wastage could be cut by 1Rheumatology, West Suffolk Hospital, Bury St Edmunds, UK dispensing only the required medication. From a person-centred care viewpoint, the NHS must do everything it can to maximize Background: NICE CG79 on RA recommends treatment with MTX in patients’ independence, as this has a positive impact on patients’ self- combination with DMARDs or MTX monotherapy if combination is not esteem and well-being. Telling patients that they have to be at home appropriate. Monthly assessment with a composite activity score is for a delivery which in 86% of cases was delivered on a morning/ recommended. In 2012 we registered patients in a national prospec- afternoon or sometimes all day timeslot basis, is an industry approach tive audit of early RA management. In RA our treatment aim is Very based on outdated concepts of what patients are capable of, and Low DAS/Remission (VLDAS) with DAS for 28 joints (DAS28) 2.6 or disempowers the individual. A universal delivery service for anti- TNF-a Low DAS (LDAS) with DAS28 2.61–3.2. At the first appointment with medication is an inefficient use of resources and should be the rheumatologist, prednisolone 20 mg is started, reducing over 6 modernized. It is clear that changing to a collection oriented service weeks. The nurse reviews at 1 week and starts MTX (usually 15 mg) has great potential benefit to a variety of groups and that this is an plus HCQ. At 5 weeks, in the nurse telephone clinic MTX is usually avenue worthy of further work. This change would reduce NHS costs escalated to 20 mg. At the 10-week nurse visit MTX may increase to while empowering patients by giving them increased control over the 25 mg. At 15 weeks, the rheumatologist may start s.c. MTX 20–25 mg, management of their condition and lifestyle. considering biologics if required. We report our audit outcomes. Disclosure statement: The authors have declared no conflicts of Methods: Between September 2012 and February 201 490 patients interest. were registered. Baseline demographics and diagnostic features were noted with drug treatment at each contact. DAS28 was recorded E48. RELATIONSHIP BETWEEN CLINICAL AND where the patient was seen face-to-face. RADIOGRAPHIC (X-RAY) DYNAMICS OF RHEUMATOID Results: Baseline: mean age 64.5 years (range 23–93 years), 59 (65.6%) ARTHRITIS AND PREDICTORS OF X-RAY PROGRESSION IN female. 46 (51.1%) had positive RF and ACPA; 11 (12.2%) solely RF PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING positive, 16 (17.8%) solely ACPA positive and 17 (18.9%) negative for CLASSIC SYNTHETIC DISEASE-MODIFYING ANTI- both. 8 (8.9%) were erosive. Earliest mean DAS28 was 4.24 (S.D.1.55).At RHEUMATIC DRUGS the latest visit, 50 (55.6%) achieved a VLDAS (44.0% being male). 13 patients (14.4%) achieved a LDAS. 19 (21.1%) had moderate activity Oleg Iaremenko1 and Ganna Mykytenko1 (DAS28 3.21–5.1). 8 (8.9%) had high activity (DAS28>5.1). At latest visit 1Internal Medicine, O.O.Bogomolets National Medical University, 60 (66.6%) took combination DMARDs, most commonly MTX plus HCQ Kyiv, Ukraine in 56 (62.2%). Each of the following were taken by 1 (1.1%) only: MTX plus HCQ plus SSZ, MTX plus LEF, LEF plus HCQ, SSZ plus HCQ. At Background: Information about the relationship between clinical and the latest visit, 19 patients (21.1%) took DMARD monotherapy: 15 X-ray dynamics in different RA duration, while different classic (16.7%) MTX, 2 (2.2%) SSZ with 1 (1.1%) on each of LEF and HCQ. 8 synthetic DMARDs (csDMARDs) are prescribed and X-ray predictors (8.9%) were on prednisolone, mean 10.8 mg (S.D. 9.6). 11 (12.2%) were of RA progression may be useful for choice of the optimal therapeutic not taking DMARDs. 3 (3.3%) patients received biologics: currently strategy. Objective: to assess the relationship between clinical and golimumab with MTX monotherapy, rituximab with MTX plus HCQ and X-ray dynamics depending on the RA duration, while different tocilizumab with MTX monotherapy. Over their entire course, 59 (65.6%) csDMARDs are prescribed and identify independent predictors of achieved a VLDAS at least once (39.0% male). 12 (13.3%) achieved X-ray RA progression. LDAS (25.0% male). 16 (17.8%) had their lowest disease activity in the E-POSTER ABSTRACTS i191

moderate range (31.2% male) and 3 (3.3%) remained in high disease latest dose, route of administration and discontinuation date with activity—all were female. reason(s). Conclusion: In this pathway, 70.0% of patients had low or very low Results: 66 had RA, 23 IPA and 11 PsA. The mean start dose was disease activity at the latest visit, and 78.9% achieved this at least once. 14.5 mg (10–15 mg, mode: 15 mg). 41 were switched to s.c. MTX Nurse clinics and telephone appointments are used alongside only two during the 5-year period for inefficacy or adverse events (AEs) in routine rheumatologist appointments. This multidisciplinary approach almost equal numbers at mean peak dose of 22 mg (7.5–25 mg, mode: produces good outcomes and increases total capacity. Biologics usage 25 mg). Of these 25 persisted to 2014, 9 returned to oral and 7 was very low at 3.3% which improves cost-effectiveness. discontinued all MTX. In 2014, 57 patients remained on MTX at their Disclosure statement: The authors have declared no conflicts of most recent visit: 32 oral mean dose 16.7 mg (5–27.5 mg, mode interest. 15 mg), 25 s.c. MTX at mean dose 21.6 mg (10–25 mg, mode: 25 mg). Of the 43 who stopped MTX: 9 were in clinical remission with DAS2.6, 19 for AEs, 14 for non-AEs, 1 was lost to follow-up. Those E50. AN AUDIT TO ESTABLISH THE CURRENT MONITORING nine with clinical remission had mean MTX duration of 137.6 weeks STANDARDS OF HYDROXYCHLOROQUINE IN PATIENTS (70.0–232.9 weeks, median: 124.0 weeks). Of 19 with AEs the mean WITH RHEUMATOID ARTHRITIS dose was 13.7 mg (5–20 mg, mode: 15 mg) and mean duration was Joseph A. Nathan1, Lee-Suan Teh1 and Kay Mitton1 61.8 weeks (range: 3.4–204.7 weeks, median 56 weeks). Patients often 1Medicine, Royal Blackburn Hospital, Blackburn, UK reported multiple AEs. Respiratory problems and gastrointestinal symptoms were cited most often (11 patients in each category), Background: HCQ is a DMARD because it can decrease the pain and each accounting for 28.2% of reported AEs. 5 patients (12.8%) cited swelling of arthritis and it may prevent joint damage and reduce the neurological problems, 4 (10.3%) fatigue, 3 (7.7%) alopecia, 2 (5.1%) risk of long-term disability. It often is used for mild RA or in weight loss, 2 (5.1%) non-specifically unwell and 1 (2.6%) abnormal combination with other drugs for more severe disease. It is well liver function tests. The mean duration in the 14 non-AEs was 106.2 acknowledged that there are rare but devastating visual complications weeks (5.0–215.0 weeks, median: 108.0 weeks), final dose mean associated with the medication and close monitoring of this is advised. 18.8 mg (5–25 mg, mode: 20 mg). Local guidelines advise the reduction of dose of HCQ within 3 months Conclusion: MTX was started at the optimal 15 mg dose and of commencing the medication. Baseline renal and liver function blood escalated to the higher doses recommended in EULAR guidance. tests and every 6 months thereafter are recommended along with an The persistence of MTX over 5 years was 57%. S.c. MTX was given in initial screening by an optician and every year subsequently. a large proportion of cases to maximize efficacy and minimize AEs with Methods: Data were collected from patients who attended the over 40% of the persisting patients using this route. The mean s.c. rheumatology outpatient clinic from November 2013–January 2014 at MTX dose is higher than the oral dose at 5 years suggesting intensive East Lancashire Hospitals NHS Trust (Royal Blackburn Hospital, escalation to achieve disease control where necessary. Only 19% Burnley General Hospital and Rossendale Hospital). All patients with withdrew for AEs unlike the 30% or more typically reported. These inflammatory or diagnosed RA and established on HCQ for 6 months patients had an effective dose for over a year. Most of the 14 non-AE or more were included. A proforma was designed to answer the withdrawals had effective doses for over 2 years. following questions; the patient’s length since diagnosed, dose and Disclosure statement: D.T.O. has received either advisory fees from period of use of HCQ, routine blood monitoring (full blood count, renal Roche, AbbVie, MSD, UCB Servier and Pfizer (previously Wyeth); and and liver function), visual assessment before commencing medication has received speaker fees and travel expenses from the Leiden and whether visual deterioration was discussed with an ophthalmol- Rheumatology Service, MSD, Menarini and Roche. All other authors ogist. Case notes and ICE desktop was used to gather the necessary have declared no conflicts of interest. information and data were inputted onto a MS Excel spread sheet. Results: A total of 46 patients (33 male and 13 female) were included E52. SUBCUTANEOUS METHOTREXATE: ARE THERE but 6 were excluded as they had been on HCQ for less than 6 months. SAVINGS TO BE MADE? Only 10% of patients had their dose calculated according to their lean body weight and 13% had it reduced after 3 months. An ophthalmol- Saajan Radia1 and Elizabeth MacPhie2 ogy history, performance of visual acuity and funduscopy at 1Manchester Medical School, University of Manchester, Manchester commencement of HCQ was poorly performed, 8%, 10% and 5% and 2Rheumatology Department, Lancashire Care NHS Foundation respectively. However 100% of patients who experienced visual Trust, Preston, UK symptoms after starting treatment were referred to an ophthalmologist and of those 67% stopped taking HCQ immediately. Only 7% of Background: MTX is an important drug in the treatment of RA and patients receiving treatment for more than 5 years were referred to an PsA. The drug can be given orally but may be changed to s.c. ophthalmologist. injections when oral MTX is not tolerated or as part of treatment Conclusion: Despite recommendation from local guidelines the escalation. However, s.c. MTX is significantly more expensive than oral reduction of dose after 3 months of HCQ is rarely performed. Visual MTX. The aim of this project was to understand how s.c. MTX is being assessment is not routinely performed and patients are overall aware used by the rheumatology team at the Minerva Health Centre and of the complications that can occur and when they should stop taking identify whether there were any potential cost savings. their medication. The findings of the audit will be presented locally to Methods: A retrospective review of all patients currently prescribed the multidisciplinary rheumatology team in order to improve care of s.c. MTX was undertaken. This involved a review of their clinical letters. these patients. There needs to be improved communication between The following information was recorded: reason for switching to s.c. the hospital staff, patient and their local optician at commencement of MTX, how long they had been on s.c. MTX and their current dose, HCQ and to ensure appropriate investigations and management are co-prescription of other DMARDs and biologics and current disease performed at initiation and while taking HCQ. We aim to re-audit in a activity. Each case was individually assessed to determine if there was year’s time. a case for switching back to oral MTX or stopping MTX in patients with Disclosure statement: The authors have declared no conflicts of PsA on anti-TNF therapy with well controlled disease. interest. Results: A total of 170 patients were prescribed s.c. MTX. 134 patients had a diagnosis of RA, 28 had PsA and 8 were prescribed for other E51. METHOTREXATE IN INFLAMMATORY POLYARTHRITIS: indications. 119 (70%) of the patients were female with a mean age of DOSE, ROUTE OF ADMINISTRATION AND PERSISTENCE 60 (range 19–88 years.) The majority of patients, 57%, were prescribed OVER FIVE YEARS doses of 20 mg or more. We were able to determine the reason for switching in 138 patients and more patients started on s.c. MTX due to William Rufus1, K. O’Reilly1, Ruth K. Slack1, Shweta S. Bhagat1, intolerance of oral MTX rather than escalation of treatment (55% v Vivek Rajagopal1 and David T. O’Reilly1 42% respectively.) 42.4% of all patients were prescribed other 1Rheumatology, West Suffolk Hospital, Bury St Edmunds, UK DMARDs and 8% were on biologics. We identified two patients with RA with well controlled disease who were switched to s.c. MTX as an Background: Oral MTX or s.c. MTX is the mainstay treatment in RA, escalation of their treatment and had subsequently been started on inflammatory polyarthritis (IPA) and PsA. Numerous studies report on anti-TNF therapy. We identified one patient with PsA now on anti-TNF tolerability and persistence. We present our data on persistence and therapy with well controlled disease. The potential cost savings by doses achieved over a five-year period in our treat-to-target service switching back to oral in the RA patients and stopping s.c. MTX in the model where treatment is intensified to achieve remission or low patient with PsA amounted to an annual saving of £2685. disease states. Conclusion: The potential cost savings identified by switching Methods: The electronic patient database was reviewed to identify the patients back to oral MTX or stopping s.c. MTX were small. first 100 patients given MTX for polyarthritis in 2009 with records However, we identified a significant number of patients on s.c. MTX, available for review at 5 years. We recorded start date, initial dose, switched for treatment escalation who did not need more expensive i192 E-POSTER ABSTRACTS

biologics to control disease activity. We recognize the need to evaluate inflammatory arthritis on long-term parenteral MTX. Retrospective this group of patients in the future but the results do suggest that s.c. case note review was performed via the electronic results and notes MTX defers the need for biologic therapy, indirectly resulting in system. Data collected included patient demographics, MTX dose, significant savings. dose adjustment, comorbidity, concomitant nephrotoxic agents and Disclosure statement: E.M. has received honoraria from Pfizer, serum creatinine (sCr). UHA provides sCr alone as a measure of renal Roche and AbbVie. The other author has declared no conflicts of function, therefore the Cockcroft-Gault equation was used to calculate interest. the estimated glomerular filtration rate (eGFR). Results: 136 patients (40 with e-RA and 96 with established parenteral MTX use) were assessed. The prevalence of CKD stage 3 was 15 % in E53. SERUM SCLEROSTIN LEVEL AMONG EGYPTIAN the eRA group and 14% in the established group. In those with CKD RHEUMATOID ARTHRITIS PATIENTS: RELATION TO BONE stage 3 only 16% (n ¼ 1) in the eRA group, and 0% (n ¼ 14) in the MINERAL DENSITY, DISEASE ACTIVITY AND RADIOLOGICAL established group had their dose adjusted (Table 1). GRADING Conclusion: This audit highlights the high prevalence of CKD in a Mervat Eissa1, Somaya Anwar1, Sahar Fakhreldin1 and relatively young population with inflammatory arthritis, with over 10% Dina Mehaney2 having CKD stage 3. Use of eGFR is recommended to guide 1Rheumatology & Rehabilitation and 2Clinical and Chemical monitoring and MTX dose adjustment as serum creatinine alone Pathology, Cairo University, Cairo, Egypt underestimates renal function. The high prevalence of nephrotoxic co- therapy and comorbidity highlights the need for vigilant monitoring and Background: Bone loss in RA is caused by increased bone resorption; prescribing in this population. There is need to develop consensus however, there is no increased bone formation. The Wnt pathway is guidance with renal physicians to ensure safe use of MTX in this important in the control of bone formation through regulation of setting. osteoblast activity. Sclerostin is an important regulator of the Wnt Disclosure statement: M.C. has received honoraria from Roche, pathway by blocking Wnt binding to its receptor and thereby inhibiting Abbott and UCB. All other authors have declared no conflicts of bone formation. An increased sclerostin expression in synovial tissues interest. of RA was found compared with OA patients Methods: Routine laboratory investigations and testing for serum sclerostin level were done. Plain radiography of the hands and feet and E54 TABLE 1. A comparison of the demographic, renal function, average MTX DXA testing were done for all patients. dose, adjustment of MTX dose according to renal function and concomitant Results: Forty RA patients, 26 (65%) were females and 14 (35%) nephrotoxic drugs and comorbidities in the MTX-established and initiation groups males. Their ages ranged from 21 years to 68 years with a mean of MTX initiation Established 48.9 11.6 years; their mean value of disease duration was 8 6.4 group (n ¼ 40) MTX group years and 40 age and sex matched apparently healthy subjects were (n ¼ 96) included. In RA patients, serum level of sclerostin ranged from 0.1 to Female, n (%) 29 (72.5) 71 (74) 1.1 ng/ml, with a mean of 0.4 0.2 ng/ml. In the controls, it ranged Age, mean (S.D.), years 57 (14.2) 59 (12.8) from 0.2 to 2.3 ng/ml, with a mean value of 0.5 0.4 ng/ml. No Average MTX dose, mg 14.9 (0.8) 19.1 (5.5) significant difference was found between RA patients and healthy sCr, mmol/l 89.5 (14.2) 82 (14.4) Average eGFR, ml/min 100 (34.8) 98 (38.4) controls as regard mean value of serum sclerostin level. CKD 1 (eGFR >90 ml/min), n (%) 23 (57.5) 49 (51.2) Postmenopausal RA patients had higher levels of serum sclerostin CKD 2 (eGFR 60–90 ml/min), n (%) 11 (27.5) 33 (34.3) than premenopausal RA patients (mean value 0.46 0.26 and CKD 3 (eGFR 30–59 ml/min), n (%) 6 (15) 14 (14.5) 0.29 0.18 ng/ml, respectively). However, it was statistically significant CKD 4 (eGFR 15–29 ml/min), n (%) 0 (0) 0 (0) on comparing healthy postmenopausal to healthy premenopausal with CKD 5 (eGFR <15 ml/min/dialysis), n (%) 0 (0) 0 (0) mean values 0.5 0.39 and 0.32 0.14 ng/ml, respectively (P ¼ 0.02). Adjustment of MTX according to sCR, n (%) 1 (16) 0 (0) Serum sclerostin had significantly positive correlations with age of RA Number with sCr in range but 6 (15) 14 (14) < ¼ ¼ ¼ ¼ eGFR 60 ml/min, n (%) onset (r 0.328, P 0.039), weight of RA patients (r 0.32, P 0.043) Concomitant nephrotoxic agents, n (%) and negative correlation with ESR in RA patients (r ¼ –0.34, P ¼ 0.03). NSAIDS 26 (65) 38 (39.6) Fourteen (35%) of RA patients had osteoporosis on DXA test. There Diuretics 4 (10) 5 (5.2) was no statistically significant correlation between serum sclerostin ACE inhibitors 3 (7.5) 10 (10.4) and BMD, disease activity or radiographic grading. Angiotensin II inhibitors 1 (2.5) 5 (5.2) Conclusion: Serum sclerostin level in RA patients did not differ Comorbidities, n (%) significantly from healthy subjects. Serum sclerostin levels have no Hypertension 10 (25) 17 (17.7) Ischaemic heart disease 2 (5) 5 (5.2) correlation to disease activity, radiographic joints damage or BMD in Diabetes mellitus 2 (5) 11 (11.5) RA. More studies on serum sclerostin levels among different grades of RA activity are encouraged. ACE: angiotensin-converting-enzyme; eGFR: estimated glomerular filtration rate; Disclosure statement: The authors have declared no conflicts of sCr: serum creatinine. interest.

E54. CHRONIC KIDNEY DISEASE AND METHOTREXATE E55. SMOKING PREVALENCE IN AN ESTABLISHED COHORT PRESCRIBING IN AN INFLAMMATORY ARTHRITIS OF RHEUMATOID ARTHRITIS PATIENTS IN A LARGE UK POPULATION TEACHING HOSPITAL Phatchrawan Tuntirungrojchai1, Marian Chan2, Christopher Sparks1 Tazeen J. Ahmed1, Leena Yalakki2 and Katie Moss3 and Nicola J. Goodson3 1Rheumatology, Croydon University Hospital, 2Rheumatology, 1Rheumatology, Liverpool University and 2Rheumatology, Mersey Kingston Hospital NHS Trust and 3Rheumatology, St George’s Deanery, Liverpool, 3Rheumatology, University Hospital Aintree, Healthcare NHS Trust, London, UK Liverpool, UK Background: Smoking is known to be a modifiable risk factor for the Background: MTX elimination is reduced in patients with impaired development of seropositive RA. It contributes 25% of the population renal function (a common comorbidity in rheumatic disease), increas- burden of RA. Those who are smokers are less likely to respond to ing the risk of MTX toxicity. There is no clear consensus on MTX dose MTX and are more likely to fail anti-TNF with a reduction of response adjustment in patients with chronic kidney disease (CKD). The 2008 to rituximab. Although the prevalence of smoking is well known in British Society of Rheumatology DMARD monitoring guidelines early arthritis (25%) smoking in established RA is less well recommend caution and close monitoring with MTX use in renal characterized. This study looks at smoking in an established cohort impairment. Guidance from the Renal Handbook, Metoject and MTX of RA patients. use in cancer patients are varied and broad. Our aim was to conduct Methods: All RA patients testing positive for ACPA from 2010 to 2013 an audit exploring: prevalence of CKD in inflammatory arthritis patients and all RA patients receiving anti-TNF treatment from 2008 to 2013 treated with MTX, MTX prescribing practices in relation to renal were contacted. 265 patients were included in the study. Patients were function and develop standard guidelines for prescribing of MTX in contacted by telephone and asked about their smoking history and rheumatology patients with CKD. efforts in cessation of smoking Methods: Two groups of patients attending University Hospital Aintree Results: 178 patients took part in the survey, (178/265, 67.2%); the (UHA) rheumatology outpatients department between January 2014 remaining patients were non-contactable, deceased or refused and June 2014, were identified: Patients with early RA (eRA) initiated participation. 76% were Caucasian, 12% Asian and 8% Afro- on oral MTX within the past 4 months and patients with established Caribbean. The average age was 58 and 74% were female.15% (26/ E-POSTER ABSTRACTS i193

178) were smokers. The mean age of smokers was 57.6 years and the Rituximab treatment was recommended. She was started on mean pack-year history was 21.1. The majority of smokers were etanercept instead due to patient’s fear of side effects. AZA was Caucasian (20/26, 75%). The majority of current smokers were male. stopped. Despite being 2 months into etanercept treatment, she 85% had tried to quit, 81% had been asked by their doctor about experienced recurrent muscle pain and limb weakness. At the same smoking and 73% had been asked to stop smoking but only 46% had time, her joints pain and swelling did not improve. Rituximab was been given support smoking. subsequently commenced, alongside with high dose oral predniso- Conclusion: 15% of the RA population were smokers. The known lone. One month following rituximab, she was reviewed in clinic, prevalence of smoking in the general population is 21.2%. A review of appeared clammy and breathless. Chest auscultation revealed fine the effectiveness of NHS smoking cessation services in 2009 crepitations in lungs. She was tachycardic at 110 beats/min. Hospital demonstrated quit rates of 53% at 1 month and 15% at 1 year. admission was felt warranted. Admission blood results revealed Offering very brief smoking cessation advice is the single most cost pancytopenia with acute renal impairment with an estimated glomer- effective and clinically proven preventative action a healthcare ular filtration rate of 16. Urine dipstick showed presence of blood and professional can take. Rheumatology outpatients may be an ideal protein. Chest X-ray was unremarkable. Direct Coomb’s test was opportunity to support patients to give up smoking and improve their negative. Blood cultures, hepatitis and HIV screen came back disease prognosis. It’s time to Ask, Advise and Act on smoking negative. On day 3 of admission, she developed pyrexia and Disclosure statement: The authors have declared no conflicts of orthopnoea and was noted to have deteriorated clinically on the interest. same day. She was intubated and ventilated prior to be transferred out of the hospital. Further immunology tests revealed acute CMV infection. Renal biopsy subsequently showed evidence of scleroderma E56. ABSTRACT WITHDRAWN renal crisis. She was treated with plasma exchange, prednisolone and valganciclovir. She was readmitted into hospital a month later with scleroderma renal crisis. The CMV PCR titre was negative. She was started on captopril. Unfortunately, she had further hospital admission E57. DOES TNF-a ANTAGONIST REDUCE RISK OF MYOCARDIAL 3 months later with diarrhoea, vomiting, pyrexia, hypotension and INFARCTION FOR PATIENTS WITH RHEUMATOID ARTHRITIS? neutropenic sepsis. CMV serology detected IgG and IgM antibodies. Daryl L. Yeo1 and Xuan Yong Lee1 She required treatment in intensive care unit. She received granulocyte 1Undergraduate Department, Manchester Royal Infirmary, colony stimulating factor, steroids, ganciclovir, meropenem and Manchester, UK vancomycin. Conclusion: This case demonstrated the complexity of the manage- Background: RA is a systemic chronic inflammatory condition that ment of connective tissue disorder and polymyositis which involved creates a pro-atherogenic state, increasing patients’ risk of myocardial several immunosuppressants. It is important to bear in mind that CS is infarction (MI). TNF-a plays a major role in stimulating this inflammatory the most basic and indispensable treatment modalities in many clinical reaction. It is hypothesized that TNF-a antagonists have a secondary aspects of rheumatic conditions, but has its immunosuppressive role in reducing MI. A literature review was done to investigate if TNF-a effect. Thorough systemic review is essential in every patient who has antagonists reduce the risk of MI in RA patients. been on sequential multiple immunosuppressive agents. Methods: A literature review was conducted to evaluate if TNF-a Disclosure statement: The authors have declared no conflicts of antagonists reduce the risk of MI in RA patients. The database of choice interest. was PubMed, and the search terms included rheumatoid arthritis, myocardial infarction, TNF-a and TNF-a antagonist. A cohort study, cross-sectional study, and four case–control studies were reviewed. E60. LIFESTYLE CHOICES AND KNOWLEDGE BASE IN Results: The BSRBR cohort study showed that overall, patients did PATIENTS WITH PSORIATIC ARTHRITIS: A QUALITATIVE not show a reduction in the risk of MI (incidence rate 1.44, 95% Cl AUDIT 0.56, 367), when compared with patients using traditional DMARDs. However, responders to anti-TNF therapy have a significantly lower Anna L. Timmis1, Morag Lenman1, Simone Castagno2, incidence rate of MI compared with non-responders (incidence rate Jonas Mmesi3, Dilrukshi Tennekone3, Yulia Peysakhova1 and 0.36, 95% CI 0.19, 0.69). The QUEST-RA study revealed that Sonya Abraham3 prolonged anti-TNF therapy could reduce MI by 58% compared with 1Imperial GP Specialty Training, Department of Primary Care and non-DMARDs (hazard ratio 0.42, 95% CI 0.21, 0.81). A case–control Public Health, 2Department of Medicine, Imperial College London study showed MI risk reduction of 80% for anti-TNF and MTX and 3Department of Rheumatology, Imperial College Healthcare NHS combination vs MTX monotherapy (RR 0.8, 95% CI 0.05, 0.88). Trust, London, UK Conclusion: TNF-a antagonists have been proved to show benefits in specific CVD risk factors such as dyslipidaemia, insulin sensitivity and Background: To examine PsA patient involvement and satisfaction in endothelial dysfunction. This review suggests that anti-TNF treatment order to review how a service may be improved. may benefit in MI incidence reduction. However, more studies Methods: A questionnaire was completed by PsA patients enquiring focusing at responders to anti-TNF therapy will be required to into their lifestyle choices, awareness of additional associated health strengthen this association. risks and their desire for annual screening health assessments. Disclosure statement: The authors have declared no conflicts of Results: 82 patients completed the questionnaire after giving informed interest. consent. 14.6% (12) of the PsA patients questioned smoked which is less than the UK national average of 20% in 2012. Of these 12 patients who smoked, 11 had considered quitting and 3 wished to be referred to E58. ABSTRACT WITHDRAWN a rheumatology based smoking cessation service. 1.2% (1) of the group admitted to a weekly consumption of over 20 units of alcohol with 85.4% (70) drinking 0–10 units. 65.9% (54) consciously tried to follow a low fat E59. CYTOMEGALOVIRUS INFECTION IN A PATIENT ON diet. Cardiovascular disease, hypertension and diabetes have all been MULTIPLE IMMUNOSUPPRESSANT THERAPIES significantly associated with PsA however only 42.7% (35) of the PsA patients questioned were aware of any additional health risks. 85.4% Elaine Y. Tang1 and Evin Sowden1 (70) would appreciate an annual health assessment. One of the top three 1Rheumatology, Pennine Acute Hospitals NHS Trust, Manchester, UK unmet patient needs evident in the free text responses was access to information on PsA, advice on lifestyle choices and associated health Background: CMV infection has been reported to occur in patients risks (mentioned in 7 responses). who received immunosuppressive therapy. It is particularly a major Conclusion: A minority of patients were aware of additional health risks cause of morbidity and mortality in immunocompromised hosts. associated with PsA highlighting a need for improvement in patient Methods: We report the case of a 56 year old woman who initially education and access to information about PsA. This could be imparted presented to rheumatologist in 1995 with painful and swollen joints. verbally, in written form or online sources. Additional resources and time Results: The patient was diagnosed with seronegative RA and spent invested in educating patients with PsA will decrease long-term received DMARDs including penicillamine and MTX. In 2010, she morbidity and mortality. An annual health assessment, which is not complained of thigh muscle pain and limb weakness. Serum creatine currently routine practice for those with PsA, as it is for RA, would lead to kinase level was raised at 16 000 U/l. Immunology tests were done and better personal and public health outcomes. Additionally availability of results showed positivity in Jo-1 antibody, SSA and SSB. Muscle lifestyle improvement opportunities and interventions could also help to biopsy subsequently revealed evidence of myopathic changes. She improve outcomes in these patients. was started on high dose oral prednisolone, followed by AZA after Disclosure statement: The authors have declared no conflicts of 2 months. 18 months later, she experienced flare up of joints pain. interest. i194 E-POSTER ABSTRACTS

E61. AN AUDIT TO ASSESS THE EFFECTIVENESS OF A effect in 97% of patients and a reduction in CRP in 80%. 37% of MANNED NURSE HELPLINE patients experienced adverse events but these led to the discontinua- 1 1 1 tion of MMF in only 9%. The results are comparable with those from Samantha Carvalho , Sandy Loader , Diana Collinson , previous studies demonstrating the effectiveness of MMF in the Julie Higgins1 and Zoe Cole1 1 treatment of large vessel vasculitis. However, this study adds weight to Rheumatology, Salisbury Distract Hospital, Salisbury, UK the evidence by incorporating larger patient numbers over a longer follow-up period. Background: Nurse helplines are an essential and integral part of the Disclosure statement: The authors have declared no conflicts of care of rheumatology patients. The service provides support and interest. empowerment not only to patients but also to their carers and families. A recent audit of our helpline suggested patients felt uncomfortable leaving messages on answerphone and there was often a delay in E63. MANAGEMENT PATHWAY FOR PSORIATIC ARTHRITIS: dealing with their queries. Feedback suggested that patients wanted IS THERE A WINDOW OF OPPORTUNITY? to be able to talk to a nurse directly. As a result a pilot was set up to provide a manned service for 2 h each day. Ganesh Kasavkar1, Anupama Nandagudi2 and Anurag Bharadwaj2 Methods: We retrospectively audited 100 patients, with a diagnosis of 1Rheumatology, Medway Maritime Hospital, Gillingham and inflammatory arthritis, at random that had utilized this service between 2Rheumatology, Basildon and Thurrock University Hospital, Basildon, April–July 2014. Patients were sent a postal questionnaire with a UK stamped address envelope for easy return. Patients were asked a variety of questions to determine how easy this service was to access, Background: PsA and RA are common chronic inflammatory arthritic how effective their query was dealt with, how the service compared condition seen in approximately 1% of the European population each. with previous and how improvement could be made. However the diagnosis is delayed due to comparatively poor Results: Of the 100 patients contacted, 67 patients replied. Of these, awareness of PsA in the community including general practitioners 94% were appropriately using the helpline for a number of queries (GPs) and patients. It has been proven that there is a window of including disease management, medication advice and test results. opportunity for autoimmune disorder like RA where an early referral 97% of patients felt that this service was helpful and their query dealt and treatment improves the outcome. We looked at the management with immediately. The vast majority of patients were able to access pathway of our cohort of PsA patients from Basildon hospital on these this service within two attempts (81%). Patients preferred this service lines. We audited our practice against the published PsA management however 40% of patients would like more hours allocated to this guidelines set by the EULAR (2011) and the British Society for service. In addition, feedback from the nurses and support staff Rheumatology (2012). providing the service suggests this service is preferable as queries are Methods: We retrospectively selected 50 patients who were diag- dealt with in real time. No complaints have been received. nosed with PsA in last 4 years at the Rheumatology Department, Conclusion: Rheumatology patients prefer manned help lines com- Basildon Hospital, and focused on the first year of the management. pared with answer phone messages as they prefer speaking directly to Results: The age of the patients ranged from 26 to 77 years of age a nurse and having their queries answered in real time. On the basis of (median 48 years, IQRL 35, IQRH 57). The male to female ratio was 1:1. this audit our helpline has been changed permanently. The median duration of symptoms was 13 months at the time of Disclosure statement: Z.C. has received honoraria from AbbVie, specialist review with more than 60% patients were reviewed after Pfizer and MSD. All other authors have declared no conflicts of duration longer than 12 months. Most patients were referred by GPs interest. (80%) and a few by dermatologists (12.5%). Looking at the subtypes of diseases, polyarthritis was the commonest pattern (55%) followed by oligoarthritis (37%). Clinicians measured the disease activity differently E62. IS MYCOPHENOLATE MOFETIL EFFECTIVE IN THE as number of tender and swollen joints (80% patients) and Psoriatic TREATMENT OF LARGE VESSEL VASCULITIS? Arthritis Response Criteria (PsARC) score (32.5% of patients). The visual analogue scale score for global disease was noted in 5% of Ruth Smith1, Kar-Ping Kuet1, Mohammed Akil1 and Rachel Kilding1 1 patients. Dactylitis and enthesitis were noted in 7.5% of patients Rheumatology, Royal Hallamshire Hospital, Sheffield, UK respectively. 67.5% of patients had normal CRP at the time of review. DMARDs were used in treatment of 65 % of patients. MTX was first Background: Primary large vessel vasculitides encompass GCA and choice in poly (77%) and SSZ in oligo (46%). Takayasu’s arteritis. The mainstay of treatment is glucocorticoids, with Conclusion: There is a significant delay between the onset of immuno-suppressants such as MTX and AZA being used as steroid- symptoms and first review by a rheumatologist. Dactylitis and sparing agents. In the Rheumatology department at the Royal enthesitis did not affect the subcategorization of disease or the plan Hallamshire Hospital, Sheffield, UK, MMF, a reversible inhibitor of of management. There were three distinct clinical patterns noted which inosine monophosphate dehydrogenase necessary for the growth of further decide the treatment pathway and outcome measures. B and T cells, has been used as an alternative immuno-suppressant. DMARDs were used frequently. Spondyloarthropathy formed a smaller There is limited data supporting its effectiveness in patients with large group. vessel vasculitis, but anecdotal evidence from clinical practice in Disclosure statement: The authors have declared no conflicts of Sheffield has shown it to be effective. The aim of this retrospective interest. study is to evaluate the effectiveness of MMF in the treatment of patients with large vessel vasculitis in terms of reduction in steroid dose, reduction in inflammation (CRP) and overall tolerability of the E64. POST-DENOSUMAB HYPOCALCAEMIA MONITORING drug. IN RENAL IMPAIRMENT Methods: A retrospective review of 35 patients with large vessel vasculitis (23 with large vessel vasculitis, 5 with TA, 4 with Takayasu’s Shuja S. Majeed1,2, Derry Wright1,2 and Stuart Webber1,2 arteritis, 2 with aortitis and 1 with GCA) taking MMF between January 1Rheumatology, Weston General Hospital and 2Rheumatology, 2008 and December 2013 was undertaken. The patient list was Weston Area Health Trust, Weston Super Mare, UK created by searching electronically saved clinic letters for the keywords large vessel vasculitis, aortitis, Takayasu’s, giant cell Background: Denosumab is licensed by NICE for the primary and arteritis, temporal arteritis and mycophenolate mofetil. Reductions in secondary prevention of osteoporosis in patients intolerant of oral steroid dose and CRP and adverse effects to MMF were assessed. bisphosphonates. Denosumab is a monoclonal antibody that Results: The patients, 29 women and 6 men with a mean age of 64, reduces osteoclast activity and hence bone breakdown. It is had been taking MMF in doses of between 1.5 g once daily to 1.5 g administered as a s.c. injection every 6 months. Summary of product twice daily for between 1 and 10 years. MMF had a steroid-sparing characteristics states no dose adjustment needed in renal impair- effect in 34 patients (97%) and in 6 cases the steroids were ment. Hypocalcaemia must be corrected before treatment. Clinical discontinued. 28 patients (80%) experienced a reduction in their monitoring of calcium is recommended before each dose and CRP over the study period and 21 (60%) had CRP of less than 5 mg/l those predisposed to hypocalcaemia within 2 weeks after initial at the end of December 2013. The mean CRP at initiation of MMF was dose. The use of denosumab in patients with renal impairment 24.1 and at the end of the study period it was 7.6. 28 patients (creatinine clearance<30) or dialysis is associated with higher risk of continued taking MMF, 25 (71%) at the highest doses prescribed. hypocalcaemia. 13 patients (37%) experienced adverse events while taking MMF, but Methods: Patients being commenced on denosumab with renal these led to the termination of treatment in only 3 cases (9%). impairment [estimated glomerular filtration rate (eGFR) <50] were 4 patients (11%) had additional medications added in to the MMF. identified. Calcium and vitamin D levels were checked prior to Conclusion: MMF is an effective and well tolerated treatment for large treatment. Patients had weekly monitoring of serum calcium levels vessel vasculitis. This retrospective review showed a steroid sparing post-denosumab treatment to monitor hypocalcaemia. E-POSTER ABSTRACTS i195

E64 TABLE 1. Weekly calcium results post-denosumab treatment Patient Denosumab Baseline eGFR Pre-treatment Post-treatment calcium results number injection calcium results date Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 1 22/01/2013 On haemodialysis 2.43 2.17 2.3 2.49 2.57 2.62 2.45 2.46 1 30/07/2013 On haemodialysis 2.92 2.93 2.53 2.4 2.72 2.71 2.66 1 28/01/2114 On haemodialysis 2.53 2.11 2.12 2.21 2.17 2.11 2.08 2.17 1 29/07/2014 On Haemodialysis 2.76 2.48 2.24 2.2 2.12 2.17 2.17 2 30/10/2012 21 2.56 1.99 2.24 2.29 2.25 2.22 2.38 2 30/04/2013 10 2.51 1.95 1.85 1.97 2.13 2.16 2.32 3 22/01/2013 21 2.18 2.29 2.21 2.26 2.31 2.12 2.29 4 14/01/2014 50 2.48 2.36 2.3 2.33 2.34 4 22/07/2014 50 2.34 2.29 2.36 2.35 2.37 5 09/09/2014 48 2.71 2.39 2.46 2.44 2.4 eGFR: estimated glomerular filtration rate.

Results: Total of five patients identified who were at risk of Conclusion: Lack of awareness of important differential diagnoses hypocalcaemia in view of renal impairment (eGFR <50). Calcium may be one factor contributing to the low uptake of appropriate levels were monitored closely on a weekly basis initially. Patient 1 management steps. Two patients audited were referred with meta- who was on haemodialysis was closely monitored post denosumab tarsophalangeal swelling, but on rheumatology review, acute knee on dialysis unit. Patient 2, on week 2 post second dose of synovitis was also present. The acute knee swelling had not been denosumab needed admission in view of hypocalcaemia which detected, reflecting either lack of full history and musculoskeletal was identified on monitoring as seen in Table 1. Patient 2 also had examination, or difficulty in recognizing synovitis, which may further hypocalcaemia after the first dose of denosumab which was explain the apparent low uptake of joint examination. Poor uptake of addressed by liaising with the renal team. The second dose of knee aspiration may reflect lack of experience or time of seniors on the denosumab precipitated hypocalcaemia despite prior treatment with medical ward to teach joint aspiration. In this audit, knee aspirations high dose vitamin D and liaison with the renal team. Subsequent done by the general medical team were performed by a CMT who had denosumab treatment was discontinued in this patient. Patients recently gained independence in knee aspiration during rotation on the with eGFR<30 and on haemodialysis were more prone to hypocal- rheumatology ward. To improve management of acute joint swelling on caemia as seen in Table 1. The number of patients is relatively small the medical ward, clinical guidelines are published within the general however weekly monitoring helped identify two patients with medical guidance folder of our trust intranet. Rheumatology registrars hypocalcaemia on blood monitoring. Also checking calcium levels and consultants also undertake supervision for knee aspiration for post-denosumab treatment weekly initially helped identify hypocal- medical trainees. A joint model in our clinical skills laboratory is also caemia earlier. available to aid teaching knee aspiration to trainees. Conclusion: Close monitoring of calcium levels in patients with renal Disclosure statement: The authors have declared no conflicts of impairment helps identify hypocalcaemia early. The Summary of interest. product characteristics recommends calcium monitoring 2 weeks post treatment in patients at risk of hypocalcaemia. The British National Formulary suggests denosumab should be used with caution in E66. A NEW DIAGNOSIS OF FIBROMYALGIA: A individuals with eGFR<30. We would recommend weekly blood QUALITATIVE EXPLORATION INTO QUALITY OF LIFE calcium monitoring initially in patients with renal impairment. Patients with low eGFR (<30) are at risk of hypocalcaemia and weekly blood Chloe Fletcher1, Greg Booth1 and Sarah-Jane Ryan1 monitoring initially can help identify patients early. 1Health Sciences, University of Brighton, Eastbourne, UK Disclosure statement: The authors have declared no conflicts of interest. Background: The diagnosis of FM is complex and, consequently, can often take a long period of time to establish. FM cannot be ruled out in a similar way to other pathologies using laboratory tests. It is known to E65. MANAGEMENT OF THE ACUTE SWOLLEN JOINT: AN mimic symptoms of similar pathologies and a conclusive pathology of AUDIT OF MEDICAL INPATIENTS FM has yet to be found. Previous studies into the effects of FM have found the condition to have detrimental consequences to a person’s Nehal Narayan1 and Rainer Klocke1 quality of life. Negative impacts on relationships, dependence on 1Rheumatology, Russell’s Hall Hospital, Dudley, UK family members, increased anxiety, depression and financial insecu- rities are just a few of the problems associated with FM. While some Background: Several published recommendations for management of people experience increased satisfaction with their health after the acute swollen joint exist: the 2006 British Society for Rheumatology diagnosis, others find the stigma linked with FM to cause increased recommendations for management of the hot swollen joint; and the anxiety. The usefulness of the diagnosis itself has, therefore been EULAR/EFORT 2009 recommendations for management of acute knee deemed questionable after considering the impact on a person’s swelling. Common to these recommendations are that affected quality of life (QOL). The purpose of this study to explore the effects of patients undergo history taking, examination of musculoskeletal diagnosis on QOL of FM patients in the initial period after diagnosis by system, blood tests to include full blood count, inflammatory markers identifying significant themes within a representative population and renal function, plain X-rays of the affected joint and aspiration of sample. the swollen joint. In this audit, we therefore set a standard of expecting Methods: The research project was approved by the University of management of 90% of patients with acute swollen joints to be in line Brighton, School of Health Professions, School Research Ethics and with these recommendations. The importance of joint aspiration is Governance Panel on 4 December 2013. A qualitative research acknowledged by the fact that knee joint aspiration is deemed an technique was used to collect data; consisting of a combination of essential GIM procedure by the JRCPTB (Joint Royal Colleges telephone and face-to-face interviews conducted using a semi- Postgraduate Training Board) for all registrars training in General structured format. Interviews were carried out by the researchers Internal Medicine, and competence is desirable at core medical trainee with nine people that had been diagnosed with FM within the last 12 (CMT or medical SHO) level. Therefore, in cases of knee swelling, we months. Interviews were recorded on a Dictaphone and transcribed documented whether knee aspiration was performed, prior to verbatim by the researchers. Braun and Clarke’s (2006) method of rheumatology referral. thematic analysis was used to analyse the data and subsequently Methods: Over 3 months, case notes of medical inpatients referred to identify any themes that arose. the rheumatology registrar with acute joint swelling (less than 6 weeks Results: Three themes emerged from the data: describing feelings onset) were reviewed. prior to and during the search for a diagnosis, the impact of the Results: 23 patients were identified. History was documented in diagnosis on QOL, and what is happening now that a name has been 18/23, examination of joints in 2/23. 16/23 had appropriate blood tests. put to their condition. Receiving the diagnosis of FM can affect a 5/23 patients had X-rays of the affected joints. No aspiration of joints person’s life both positively and negatively. It can influence their other than knees was undertaken prior to rheumatology referral. 15/23 psychological state, relationships with family, friends and employers, patients had knee swelling. 3 had knee aspiration prior to rheumatol- social activities and occupations. ogy referral: one was done by orthopaedics, and two knee aspiration Conclusion: The researchers recommend that future studies be procedures were done by a renal CMT. Median time to rheumatology carried out on an international level with a larger population. Exploring referral was 4 days. the effect diagnosis can have on people with FM provides valuable i196 E-POSTER ABSTRACTS

information to contribute toward the body of evidence on the condition WOMAC and SF-36 scores. The gender differences suggest that for and the importance of early diagnosis. Diagnosis emerged as a similar knee OA X-ray grade women’s clinical scores are lower. defining point throughout the study, emphasizing the need for greater Disclosure statement: The authors have declared no conflicts of awareness particularly in primary care, to ensure early diagnosis and interest. better support for those affected. Disclosure statement: The authors have declared no conflicts of interest. E69. ASSOCIATION OF SERUM LEPTIN LEVELS WITH KNEE OSTEOARTHRITIS IN A SAMPLE OF IRAQI FEMALE PATIENTS Sami Salman1 and Zahraa Al-Jallili1 E67. ENHANCED CLOSED KINEMATIC CHAIN 1Rheumatology, Medical College University of Baghdad, Baghdad, BIOMECHANICAL THERAPY FOR PATIENTS AFTER TOTAL Iraq KNEE ARTHROPLASTY Lee Yaari1, Yona Kosashvili1, Ganit Segal2, Shai Shemesh1, Background: OA is a biomechanical process whereby joints respond Steven Velkes1, Ronen Debi3, Amit Mor2, Benjamin Bernfeld4 and pathologically to mechanical stress, resulting in cartilage degradation Avi Elbaz2 and changes in subchondral bone. It has many risk factors as known 1Department of Orthopaedic Surgery, Rabin Medical Centre, Petah female gender, obesity and ageing. Leptin is a peptide hormone Tikva, 2AposTherapy research group, AposTherapy, Herzliya, secreted by adipocytes and plays an important role in regulation of 3Department of Orthopaedic Surgery, Barzilay Medical Centre, body weight, its level is more in obese subjects and in female gender 4 regardless of obesity, so it may play a metabolic link between obesity Ashkelon and Department of Orthopaedic Surgery, Carmel Medical and OA. The study objective is to examine the cross-sectional Centre, Haifa, Israel association of serum leptin level in a sample of Iraqi females with knee OA. Background: Many factors contribute to suboptimal results of total Methods: A total of 90 female patients with knee OA (KOA) and equal knee arthroplasty (TKA). Little is known regarding the value of post- number of their matched healthy controls. OA was diagnosed surgical rehabilitation after TKA. We examined the effect of an according to ACR criteria for OA and their BMI classified according enhanced closed kinematic chain exercises programme on gait to WHO classification of BMI into three groups: normal weight, patterns and clinical outcomes among patients with a lack of progress overweight, obese. Radiological grading done according to Kellgren in their post-surgical rehabilitation. and Laurence radiological classification for OA. Serum leptin level was Methods: Twenty-two patients were prospectively followed during the assessed using the ELISA method. study. Gait spatiotemporal parameters were measured at initial Results: Leptin was significantly higher in cases compared with evaluation, after 15 min of therapy and at 3 months. Western Ontario controls; the mean serum leptin was (52.41 28.26) and and McMaster Osteoarthritis Index (WOMAC) and short form 36 (40.39 25.67), respectively. Its level directly correlated with BMI, (SF-36) questionnaires were filled in by patients before treatment and higher levels in obese and overweight than normal weight subjects, after 3 months of treatment. and the difference was significant among both cases and controls. Results: WOMAC and SF-36 scores significantly improved after 3 Association of leptin levels with radiological grading, the mean serum months of treatment. Gait velocity, single limb support (SLS) and step leptin was higher in cases with grade III and IV than grade II. length of the operated leg significantly improved even after a single Conclusion: Serum leptin level was higher in female patients with knee 15-min treatment. Normal gait velocity appeared among 36% of OA compared with their matched controls, and its level was directly patients after 3 months of treatment. associated with increased BMI. Conclusion: We found rehabilitation using enhanced closed kinematic Disclosure statement: The authors have declared no conflicts of chain biomechanical therapy to be potentially beneficial for patients interest. post-TKA who experience a suboptimal rehabilitation course. The expected time for a consolidated improvement is 3 months. Disclosure statement: G.S. is an employee of AposTheray. R.D. is a E70. A COMPARISON OF TWO HYALURONIC ACID shareholder of AposTherapy. A.M. is a shareholder of AposTherapy. PREPARATIONS IN PATIENTS WITH KNEE OSTEOARTHRITIS

A.E. is a shareholder of AposTherapy. All other authors have declared 1 1 1 no conflicts of interest. Maliha Shaikh , Venkat Reddy and Dev Pyne 1Rheumatology Department, The Royal London Hospital, London, UK E68. GENDER DIFFERENCES IN THE RELATIONS BETWEEN CLINICAL QUESTIONNAIRES AND RADIOGRAPHIC GRADES Background: Intra-articular HA for knee OA is not recommended by IN KNEE OSTEOARTHRITIS: A CROSS-SECTIONAL NICE based on cost-benefit analysis. However the debate continues EVALUATION OF 518 PATIENTS as there is evidence from systematic reviews and meta-analyses such as the Cochrane Review, 2006 and the EULAR Taskforce 1,2 3 4 5 Amir Herman , Ofir Chechik , Ganit Segal , Yona Kosashvili , Recommendations, 2003 for its effectiveness in pain reduction. 3 3 4 4 3 Ran Lador , Moshe Salai , Amit Mor , Avi Elbaz and Amir Haim Synthetic HA preparations may be of high molecular weight 1 2 Department of Orthopaedic Surgery, Talpiot Medial Leadership (Synvisc-like) or low molecular weight (Ostenil-like). Barts Health 3 Programme, Sheba Medical Centre, Tel Hashoner, Department of changed the funding approval from Synvisc One in 2011 to Ostenil Orthopaedic Surgery, Sourasky Medical Centre, Tel Aviv, Plus in 2013, based on the cost of an injection vial of £215 and £96, 4Apostherapy Research Group, AposTherapy, Herzliya and respectively. We therefore sought to audit the efficacy of each agent in 5Apostherapy Research Group, Rabin Medical Centre, Petah Tikva, real clinic patients after a single injection for knee OA. Israel Methods: Patients were deemed suitable for HA injection if they had confirmed OA of the knee (Kellgren grade II–IV), were unable to tolerate Background: To evaluate the correlations between common clinical or had not responded to oral NSAIDs, intra-articular CSs and were OA diagnostic tools in order to determine the value of each. A unsuitable for knee replacement. All patients attending the secondary goal was to investigate the influence of gender differences Rheumatology Department who met these criteria were offered on the findings injection with Ostenil (post-2013) or Synvisc (2011–2012). Patients Methods: Five hundred and eighteen patients with knee OA were recorded pain scores [pain visual analogue scale (VAS)] score on a evaluated using the Western Ontario and McMaster Osteoarthritis scale of 0 (no pain) to 10 (worst pain) pre-injection, 2 hourly for 24 h, Index (WOMAC) questionnaire, short form 36 (SF-36) Health Survey daily for a week, alternate days for a month, at 6 weeks, 3 months, 4 and plain radiographs. Analysis of variance (ANOVA) was used to months and 6 months post-injection. All patients gave informed compare the different domains of the WOMAC and SF-36 ques- consent. Statistical analysis: Mann–Whitney U test or paired Student’s tionnaires between genders and the radiographic scale. t-tests were used to compare the groups as appropriate, using a 5% Results: Higher knee OA X-ray grade were associated with worse significance level throughout. clinical outcome: for women, higher scores for the WOMAC pain, Results: We included 33 patients with knee joint OA with a mean age function and final scores and lower scores in the SF-36 final score; in of 67.4 years (range 25–85) and 25 were female. Twenty patients men, lower SF-36 overall and physical domains scores. Gender received Ostenil to 32 joints and 13 received Synvisc to 14 joints and differences were found in all clinical scores that were tested, with the duration of follow-up was 6 months. There was significant women having worse clinical scores for similar radiographic grading improvement in pain VAS from baseline at all time points with both (P-value <0.001). preparations (P-values shown in Table 1). Despite a significantly higher Conclusion: Knee radiographs for OA have an important role in the baseline VAS in the Ostenil group, there was no significant difference clinical evaluation of the patient. Patients with higher levels of knee OA in VAS between the two groups at 1, 3, 4 and 6 months after treatment. in X-ray have a higher probability of having a worse clinical score in the Average pre- and post-treatment pain VAS scores are tabulated E-POSTER ABSTRACTS i197

E70 TABLE 1. VAS scores at baseline and 1, 3, 4 and 6 months post-injection Pre-treatment VAS VAS 1 month VAS 3 months VAS 4 months VAS 6 months post-injection/10 post-injection/10 post-injection/10 post-injection/10 Ostenil Plus Mean (S.D.) 7.78 (1.96) 4.22 (3.28) 4.84 (3.09) 4.97 (3.05) 4.95 (2.91) Median 8 4 4 4 5.5 n 32 32 31 31 20 P-value — <0.0001 <0.0001 <0.0001 <0.005 Synvisc One Mean (S.D.) 6.8 (0.89) 4.57 (2.65) 4.14 (2.07) 4.14 (2.79) 3.86 (2.97) Median 7 6 4 3 3 n 14 14 14 7 7 P-value — <0.005 <0.0001 <0.05 <0.05 VAS: visual analogue scale.

below. Maximum benefit was seen at 1 month but the difference from E71 TABLE 1. Average pain change after injection baseline VAS scores remained significant at 6 months with an average reduction in VAS of 36% for Ostenil and 43% for Synvisc. Condition Average Average Improved in Average Improved in Conclusion: HA injections in our sample led to a significant VAS VAS 6 weeks, % VAS 3 months, % improvement in pain VAS for up to 6 months. HA injections seem a before 6 weeks 3 months injection after after useful adjunct in knee OA with a single injection of Ostenil Plus as injection injection effective but cheaper than Synvisc One in our cohort. Inflammatory 7.65 3.54 53.72 3.75 50.98 Disclosure statement: The authors have declared no conflicts of arthritis interest. Primary OA 7.81 2.5 67.98 4.5 42.38 Total 7.73 3.06 60.41 4.85 37.25 VAS: visual analogue scale. E71. CORTICOSTEROID INJECTIONS FOR ARTHRITIS OF HIP JOINT Background: Osteoporosis is a deterioration of skeletal bone, which, Matara A. I. Kulasinghe1 and Chandrabhusan Chattopadhyay1 although common in those over 50 years of age, still exists in those 1Rheumatology, Wrightington Hospital, Wigan, UK below that age range. There is currently no standard definition of osteoporosis in this age group, and there is very limited current Background: OA of the hip joint is a painful debilitating condition. evidence about the predictors of the disease in those aged below 50. NSAIDs and other analgesics are unsuitable for many patients This study focuses on the identification of predictors of low BMD in an especially in elderly patients. Intra-articular injection of local steroid under-50 cohort. is accepted as treatment modality by NICE. At Wrightington Hospital, Methods: Data from 3872 patients under 50 years of age undergoing we regularly carryout intra-articular injections of hip joints for DXA were included in the study. Linear regression analysis was used to inflammatory and non-inflammatory arthritis. We wanted to evaluate investigate significant predictors of low BMD, adjusting for age. the effect of this treatment method including effects of various Results: Significant results for total mean hip BMD (age adjusted) variables if any on the final outcome predictors were weight, BMI, number of indications for scan and a Methods: It is a service evaluation of fluoroscopic guided injections to family history of fracture. Significant L1–L4 BMD (age adjusted) the hip joint with 80 mg Depo-Medrol and 7.5ml of 0.9% saline. All the predictors were height, weight, Index of Multiple Deprivation score, patients who have undergone steroid injections to the hip joint after number of indications for scan, family history of fracture, age at scan, April 2014 were included for evaluation. Patients were informed about BMI and any tobacco use. the project and consent was obtained. On the day of injection following Conclusion: Predictors of a low BMD in the under 50s varied according information were recorded. BMI, pain in visual analogue scale, to anatomical location and sex. The only consistent predictor across both duration of the pain, analgesics consumption, range of movements, sexes and anatomical locations was the number of indications for scan. other comorbidities, imaging details and the diagnosis. At 6 weeks the Disclosure statement: The authors have declared no conflicts of patients were interviewed over the phone on relief in pain and changes interest. in the consumption of analgesics and anti-inflammatory medication. At 3 months patients were seen in the follow-up clinic and re-assessed. X-rays of the patients were reviewed and graded according to E73. AUDIT OF TERIPARATIDE USE IN OSTEOPOROSIS: TO Lawrence–Kellgren scale. ASSESS ADHERENCE TO NICE GUIDELINES AND Results: 25 hip joints in 19 patients were injected. Seven patients had TREATMENT RESPONSE bilateral injections. There were 3 males and 16 females. On the day of injection exacerbation of pain, difficulty in walking and fever was not Aisha Ghouma1 and Keeranur Jayakumar2 experienced by any of the patients. The age range was 38–89 years. 1Rheumatology, Russell’s Hall Hospital, Dudley and 2Rheumatology, There were seven RA, eight primary OA and four other inflammatory HEFT, Solihull, UK arthritis patients. Average radiation exposure was 1.8 mGy/m2.At6 weeks, 33.3% showed more than 80% improvement and 62.46% Background: Teriparatide, a recombinant fragment of human PTH, is showed more than 50% improvement in pain. 16 patients reduced the an anabolic agent indicated for the secondary prevention of analgesics in 6 weeks. In 3 months, 6.63% showed improvement in osteoporotic fragility fractures in postmenopausal women. It stimu- flexion, 17.56% improvement in internal rotation and 4.47% improve- lates new formation of bone and increases resistance to fracture. ment in external rotation observed. Teriparatide yearly cost is around £3544. The primary objective of this Conclusion: More than 60% of patients have shown >50% improve- audit is to measure current practice at the Heart of England ment in the pain in 6 weeks of injection. A 3-month evaluation was Foundation Trust against NICE guidance on use of teriparatide. We done only in 12 patents in this ongoing study. There is no significant also aimed to audit treatment response to teriparatide. improvement in joint movements after steroid injections. We expect to Methods: Retrospective analysis of patients with osteoporosis who recruit about 75 patients by next March when 6 months data would be used teriparatide between 2012 and 2014. Data collected from the I- available. care electronic system. Disclosure statement: The authors have declared no conflicts of Results: 15 postmenopausal women with established osteoporosis interest. identified. Adherence to NICE guidelines was assessed. The use of teriparatide in 14 out of 15 (93%) was as per NICE recommendations. One patient had teriparatide for osteonecrosis of the jaw while on E72. PREDICTORS OF LOW BONE MINERAL DENSITY IN alendronate. All used bisphosphonate or strontium before teriparatide MEN AND WOMEN UNDER 50 YEARS OF AGE (100%). The response to treatment was satisfactory in 5/15 (33%); unsatisfactory in 3/15 (20%), one had a neck of femur fracture and the Chloe Egerton1, Luke Farrow2, Alex Oldroyd3 and Marwan Bukhari3 second had fracture of 5th metatarsal (despite an improved T-score); the 1Lancaster University, Lancaster, 2Department of , response was not clear in 7/15 (47%), 2 were still on treatment, 3 did not Glasgow Royal Infirmary, Glasgow and 3Department of have repeat DXA, one could not tolerate treatment and one was Rheumatology, Royal Lancaster Infirmary, Lancaster, UK deceased. i198 E-POSTER ABSTRACTS

Conclusion: Excellent compliance with NICE guidelines in initiating from the AS clinic database. They completed a questionnaire after teriparatide. 2 out of 12 patients who received treatment suffered informed consent which combined validated measures of disease fragility fractures after treatment. It is difficult to draw conclusions on activity: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); bone density improvement because DXA was performed only in the Bath Ankylosing Spondylitis Functional index (BASFI) with quality 7 patients. of life; and the Ankylosing Spondylitis Quality of Life (ASQoL). Cases Disclosure statement: The authors have declared no conflicts of were compared with controls using descriptive statistics (IBM SPSS interest. version No 22). Results: A total of 203 subjects were identified and approached. Response rates were 56.2% in CA and 30.3% in NA (CA n ¼ 77, NA E74. A CROSS-SECTIONAL SURVEY OF MANAGEMENT n ¼ 20) and showed non-attendance at clinic was due to a location and PRACTICE OF PSORIATIC ARTHRITIS IN ESSEX UK timing of the clinic, failure to receive appointments and patient Ganesh Kasavkar1, Anupama Nandagudi2 and Anurag Bharadwaj2 perception of feeling well. Feedback regarding clinic effectiveness 1Rheumatology, Medway Maritime Hospital, Gillingham and was similar between the two groups with mainly positive feedback and 2Rheumatology, Basildon and Thurrock University Hospital, Basildon, UK 27% CA suggesting no change was required to the clinic. However, the key areas for improvement included holding clinics closer to Background: PsA is a chronic inflammatory arthritis as prevalent as patients and better support in clinic allowing for continuity of care. No RA—affecting approximately 1% of the European population. PsA statistical differences were seen between the groups in terms of management has evolved in the last few years with increasing BASDAI, BASFI or ASQoL. Patients with a BASDAI score 4 were awareness, advent of biologics and publication of international seen in both groups. There were no statistically significant differences guidelines e.g. Grappa, EULAR and the British Society for between CA and NA in terms of demographics, employment status or Rheumatology (BSR). We looked at the current practice of PsA index of social deprivation. CA were more likely to be on NSAIDs than management among the clinicians and compared it with the published NA. recommendations (EULAR and BSR guidelines). Conclusion: Reasons for non-attendance were multifactorial and Methods: We conducted a survey among the clinicians practising differed from patient to patient. Although the numbers in this study are rheumatology in Essex to analyse their practice for the management small and there may be a self-selection bias, the study shows that PsA. The survey was based on questionnaire about referral pattern, patients who stop attending the clinic (NA) perceive their disease to be use of classification criteria, subcategorization, investigations, treat- better controlled or have better coping mechanisms even though they ment modalities and reasoning for the same. may have BASDAI scores similar to CA. Some valuable suggestions Results: We received total of 28 responses, i.e. 21 from consultants, have been made by patients in both groups which will be addressed to 5 from registrars and 2 from nurses. Referrals for patient review came improve compliance and patient care in the AS clinic in the future. from general practitioners (80%) and dermatologists (17%) for PsA Disclosure statement: The authors have declared no conflicts of assessment. Rheumatologists referred patients to Dermatology mostly interest. for severe skin involvement (68%). CASPAR criteria for diagnosis were used by 54% of clinicians with only 10% always using it. For subcategorization Moll and Wright criteria was used most commonly. Most clinicians did not sub categorize or treat enthesitis (78%) and E76. AN AUDIT OF THE TREATMENT OF PSORIATIC dactylitis (85%) differently. DMARDs were used by 79% of the ARTHRITIS WITH BIOLOGICS clinicians for oligoarthritis and MTX use was highest (71%) followed Charlotte Rawlings1, Anurag Negi1 and Ernest Choy1 by SSZ (46.3%). In polyarthritis MTX was used by all clinicians as first- 1Rheumatology, University Hospital of Wales, Cardiff, UK line agent while SSZ was the preferred second-line agent (78.6%) followed by LEF (14.3%).The reasons given for the use of MTX as first- Background: February 2014 audit of the 2012 British Society for line agent were due to efficacy (39%), works for both skin and joints Rheumatology (BSR) guideline for the treatment of PsA with biologics (14.3%), evidence based (10.7%). The reasons for use of SSZ as (published July 25 2013). The previous BSR guidelines were written in second-line agent were efficacy (18.5%), safety (11.1%), experience 2005 when anti-TNF was not as widely available. Etanercept, (7.4%), good for enthesitis (3.7%). Disease outcome measures were infliximab, adalimumab and golimumab are recommended for the used by 75% clinicians with PsARC (Psoriatic Arthritis Response treatment of adults with active and progressive PsA when the criteria Criteria) being the commonest (76%) followed by DAS for 28 joints are met. Certolizumab has been added to this list with NICE approval (DAS28; 19%). Spinal involvement presenting as psoriatic spondyloar- in June 2014. thropathy were treated as AS by 65% of the clinicians. Biologic agents Methods: To audit the 22 patients started on biologics between 25 were used by 68% of the clinicians with adalimumab being the July 2013 and 28 Feb 2014. Data were collected using a combination commonest agent (63%), reason being efficacy (44%). of electronic and paper notes and applying the BSR PsA Audit Tool. Conclusion: Enthesitis and dactylitis do not contribute to the Results: Of the 22 patients with PsA, none of the patients had axial subcategorization or management choices of psoriatic arthritis in our disease. Phenotype analysis showed that 23% had nail psoriasis, 27% cohort. The use of PASI (Psoriasis Area and Severity Index)/body dactylitis and 36% enthesitis. 9% of patients had >10% body surface surface area score for assessment of skin involvement is rare by area of psoriasis and 18% had seen the dermatologist. Of the patients rheumatologist. There was high use of DMARDs even in oligoarticular with peripheral disease, the most used TNF inhibitor was adalimumab PsA. MTX is the preferred first-line agent. Majority of clinicians treat AS (13/22), followed by etanercept (5/22), golimumab (3/22) and infliximab and psoriatic SpA similarly. Among the biologics, adalimumab is (1/22). 2/22 had adverse indicators including raised CRP 5 and preferred. swollen or tender joints or structural joint damage due to disease. The Disclosure statement: The authors have declared no conflicts of most popular first-line DMARD was MTX (13/22), then SSZ (4/22), interest. Ciclosporin (3/22), AZA (1/22) and HCQ (1/22). The second-line most popular DMARD was LEF (7/22), MTX (5/22), SSZ (5/22) and E75. FACTORS AFFECTING NON-ATTENDANCE AT THE Ciclosporin (4/22). The most common failure for first and second ANKYLOSING SPONDYLITIS CLINIC AND ITS EFFECT ON DMARD therapy was inefficacy at 12/22. All patients who were HEALTH OUTCOMES reviewed at 12 weeks had a Psoriatic Arthritis Response Criteria (PsARC) evaluation but 6/22 patients had not had a 12 week review. Karen Secombes1, Neil Basu1, Lesley Davidson2 and Ejaz M. Joint counts at initiation of therapy showed that 20/22 were eligible. 1 I. Pathan2 patient, however, did not have adverse indicators and had <3 tender 1Musculoskeletal Research Group, University of Aberdeen and and swollen joints. 2Rheumatology, Aberdeen Royal Infirmary, Aberdeen, UK Conclusion: 100% of PsA patients that were started on biological therapy between 25 July 2013 and 28 February 2014 had peripheral Background: The AS clinic in Aberdeen is a physiotherapist led clinic disease. It is unclear whether these are true results or that axial PsA is with medical input from junior medical staff. A recent audit found being classified as AS. The majority patients were on Adalimumab. The almost half of the patients had been lost to follow-up. Reasons for non- most used first-line DMARD was MTX and second-line was LEF. None attendance were not known and the health status of the non-attending of the patients had Psoriasis Area and Severity Index (PASI) individuals was a cause for concern. We aimed to identify reasons for assessments but two had severe skin disease and four had seen a non-attendance at a specialist AS clinic with view to informing service dermatologist. Six patients were not reviewed at 12 weeks. reconfiguration, and establish whether non-attenders (NA) reported Recommendations: father audit to establish if patients on anti-TNF inferior clinical outcomes to clinic attenders (CA). are being wrongly classified as having AS rather than axial psoriatic Methods: A case–control study was conducted, in which cases were arthritis. There is a need for a greater awareness of the anti-TNF defined as NA and controls were defined as CA. All subjects eligibility criteria for axial PsA. Assess the need for dermatology review (diagnosed by clinicians and referred to the service) were identified if psoriasis >10% body surface area. 12 week review with E-POSTER ABSTRACTS i199

PsARC PASI. PASI training for rheumatology staff would be helpful at the last session to assess their satisfaction with the group. This to aid a more rounded approach to assessment of biologic efficacy. utilized Likert scales in response to a number of questions. Disclosure statement: The authors have declared no conflicts of Results: In total 70 patients started the group, 49 patients completed interest. the group and were included in the analysis. 84% were female with a mean age of 49.6 years (range 23–71 years.) The FIQR total score improved in 33 patients, post-course. However, the improvement was E77. INVOLVEMENT AND SATISFACTION IN PATIENTS WITH not statistically significant (P ¼ 0.18). There was no correlation PSORIATIC ARTHRITIS: A QUALITATIVE AUDIT between outcome and age, pain duration or baseline FIQR. Twenty- Anna L. Timmis1, Morag Lenman1, Simone Castagno2, six patients (53%) returned the 6 month follow-up FIQR. Of these, 14 Jonas Mmesi3, Dilrukshi Tennekone3, Yulia Peysakhova1 and maintained or improved their FIQR score (vs post-course). Overall Sonya Abraham4 reduction in FIQR score (baseline vs follow-up) still failed to reach 1Imperial GP Specialty Training, Department of Primary Care and significance (P ¼ 0.13). The satisfaction questionnaire demonstrated Public Health, 2Department of Medicine, Imperial College London, that patients had a better understanding of their condition with 100% 3Department of Rheumatology, Imperial College Healthcare NHS strongly agreeing or agreeing with this statement. 94% also agreed or Trust and 4Department of Rheumatology, Imperial College London, strongly agreed that they no longer felt they would need to see their GP London, UK as frequently regarding their condition as they did before the course. Conclusion: Overall, analysis and feedback is encouraging, although Background: To examine PsA patient involvement and satisfaction in improvements in FIQR scores did not reach statistical significance. A order to review how a service may be improved. significant frustration for the team is the high dropout rate, though Methods: A questionnaire was completed by patients with PsA when patients complete the group patient satisfaction is high. The enquiring into the diagnostic process and involvement in treatment team are considering ways in which to improve attendance and ensure decisions. best use of resources. Results: 82 patients completed the questionnaire. 54.9% (45) of Disclosure statement: E.M. has received honoraria from Pfizer, patients had to see their general practitioner (GP) three or more times Roche and AbbVie. The other author has declared no conflicts of before being referred to a specialist. 50% (41) of patients felt satisfied interest. regarding the time interval from initial presentation to specialist assessment. 81.7% (67) were referred to a rheumatologist as opposed E79. FATIGUE IS COMPARABLE BETWEEN FIBROMYALGIA to a dermatologist in the first instance. 87.8% (72) had been involved AND SPONDYLOARTHRITIS: DIFFERENCES BETWEEN FM as much as they wanted in the management of their condition. 93.9% AND HLAB27(þ) SPA WITH REGARD TO THE MAIN (77) had confidence in the doctors treating them and 95.1% (78) felt MUSCULOSKELETAL COMPLAINT AS PERCEIVED BY THE doctors addressed concerns and provided clear explanations. In the PATIENTS free text responses the top three themes which were mentioned were: coordination and communication between the rheumatology and Aicha Bouraoui1, Andreas Georgiou1 and Euthalia Roussou1 dermatology services and primary and secondary care (mentioned 1Rheumatology, King George Hospital, London, UK on 10 occasions), access to specialist routine and emergency appointments (9 occasions) and a desire for more information about Background: Aiming to assess clinical differences between FM and PsA (7 occasions). SpA, patients seen in clinic with primary FM (n ¼ 50) and HLAB27(þ) Conclusion: A delay in early referral is evident. Patient education, SpA (n ¼ 69) were asked to complete questionnaires. Both ques- increased awareness of PsA in primary care and resources such as the tionnaires have the same question: what is the main musculoskeletal Psoriasis Epidemiology Screening Tool questionnaire in primary care problem that the disease is causing to you? could aid early referral. Communication between disciplines, access to Methods: All patients seen in routine rheumatological clinics and appointments and patient explanation should be addressed. Barriers clinically assessed and other conditions were excluded aiming to have to funding, coordination and communication between primary and a unified cohort. SpA patients only having the HLAB27(þ) locus were secondary care also need to be reviewed. A joint rheumatology and included. Patients had to choose any (one or more) from a list of eight dermatology service would certainly improve coordination of care items: fatigue, neck pain, upper back pain, lower back pain, stiffness, between these interrelated specialties for patients with PsA and may joint pain/swelling, pain with pressure on various areas and other. be more cost effective. Innovative means of communicating informa- Under the category other they could add anything not listed. 90% CI tion to patients could involve online resources and patient education levels were used to assess statistical significance difference between forums. Further research needs to be undertaken to examine the the two groups. The study has taken place locally and gained ethics benefits of early review and multispecialty review for patients with PsA. approval. Disclosure statement: The authors have declared no conflicts of Results: All FM patients were females while the SpA group had 30 interest. males and 39 females. The mean age of the initial symptom was 34 years ( 10) for the FM group (range 14–52 years) and 27 years (12) for the SpA group range (7–59 years). At 90% confidence level, the E78. EVALUATION OF THE FIBROMYALGIA EDUCATION difference in the mean age of initial symptom was statistically GROUP AT THE MINERVA HEALTH CENTRE significant between the two groups (P > 0.05). Our main result Samuel Naylor1 and Elizabeth MacPhie2 showed that fatigue occurred in similar percentage in both groups 1Manchester Medical School, University of Manchester, Manchester (42%) in FM and (49.3%) in SpA (P > 0.05). Under other symptoms and 2Rheumatology Department, Lancashire Care NHS Foundation noted by patients in FM group were: dizziness, headaches, stomach Trust, Preston, UK pain, sleep disturbance, lack of concentration, swollen ankles, muscle aches and shoulder pain. Background: The management of FM requires a multidisciplinary Conclusion: Fatigue was the only symptom from those listed that approach which should include a combination of pharmacological and occurred in similar percentage in both groups. Back pain (upper and non-pharmacological interventions. With limited resources available to lower), neck pain, stiffness, pain with pressure and even joint pains rheumatology departments it is not possible to provide individually have been recorded in higher percentages in the FM group in a tailored self-management programmes. Many units now deliver self- statistically significant manner. management programmes to groups of patients with FM. In January Disclosure statement: The authors have declared no conflicts of 2013 the Rheumatology Department at the Minerva Health Centre interest. established a Fibromyalgia Education Group delivered by occupational therapists and consisting of four sessions covering topics including: E80. SECONDARY FIBROMYALGIA IN PATIENTS WITH routine setting and pacing, managing stress and relaxation techniques, OTHER RHEUMATIC DIAGNOSES: CLUES FOR RECOGNITION managing unhelpful thoughts and graded exercise. The aim of this ON A MULTIDIMENSIONAL HEALTH ASSESSMENT project was to evaluate the effectiveness of this Fibromyalgia QUESTIONNAIRE AND PHYSICIAN RHEUMDOC CHECKLIST Education Group using the revised FM impact questionnaire (FIQR) and a patient satisfaction questionnaire. Theodore Pincus1, Elena Nikiphorou2, Annie Huang1 and Methods: Patients attending the group were asked to complete an Isabel Castrejon1 FIQR at the first (baseline) and last (post-course) sessions. A follow-up 1Rheumatology, Rush University Medical Center, Chicago, IL, USA FIQR was sent out in the post 6 months after completion of the group and 2Rheumatology, Addenbrooke’s Hospital, Cambridge, UK (follow-up.) Data were analysed for significant reductions in FIQR total score. Coefficients of variance were used to identify any correlation Background: 20–40% of patients with various rheumatic conditions between outcomes and patient variables. Statistical significance was are recognized to have concomitant comorbid FM, which often set at P < 0.05. Patients were also asked to complete a questionnaire complicates patient management. Secondary FM may be difficult to i200 E-POSTER ABSTRACTS

recognize in patients who meet criteria for RA, SLE and other diseases. interacted with the expert panel and delegates. The day was funded by A 2-page multidimensional health assessment questionnaire (MDHAQ) the local rheumatology endowment fund and refreshments provided and 1-page RHEUMatology DOCtor (RHEUMDOC) checklist include by AbbVie. The day was free for delegates to attend. scales that provide clues to FM. We analysed MDHAQ and Results: Feedback was obtained from 34 out of 45 delegates via RHEUMDOC scales in patients with various rheumatic diseases who SurveyMonkey. 76.47% had never previously attended any educa- were designated by their rheumatologists as having or not having tional sessions on HMS. Feedback for the guest speakers in the secondary FM. morning was positive. 88% found the lecture given by Dr Hakim Methods: All patients seen in a clinical setting complete a 2-page extremely useful; attendees found it useful to go over the nomen- MDHAQ in 5–10 min in the waiting area, prior to seeing the clature and overlap between HMS and Ehlers–Danlos syndrome. rheumatologist in routine care. The MDHAQ includes physical function Feedback was similarly positive for other speakers. 94% found the (FN) in 10 activities scored 0–3, total 0–30 converted to 0–10 and 0–10 afternoon case reports extremely or very helpful. 67% reported that visual analogue scale (VAS) scores for pain (PN), patient global score they would still have attended if there had been a fee for the day. (PATGL) and fatigue (FT), a 0–60 item symptom checklist and Overall comments from the day highlighted the educational benefits; demographic data. RAPID 3 (0–30) is the sum of scores for FN, PN delegates praised the organization of the day, the variety of different and PATGL. RHEUMDOC is a one-page physician checklist with four aspects addressed in the case presentations and felt that their 0–10 VAS physician global estimates to assess overall patient status practice would change as a result of the study day. (DOCGL), inflammation (reversible signs; DOCINF), damage (irrever- Conclusion: This was the first multidisciplinary study day on HMS in sible signs; DOCDAM) and neither inflammation nor damage South Wales. New ideas were generated and delegates felt more (DOCNON), e.g. FM. All patients were classified as having or not confident in managing such patients in future. We would recommend having a secondary diagnosis of FM, and compared for mean scores the organization of similar study days in other units. One suggestion for on MDHAQ and RHEUMDOC scales, using t-tests to analyse improvement would be to involve psychologists as the attendees felt statistical significance. this would have enhanced the learning experience. Results: Of 311 patients with various rheumatic diagnoses other than Disclosure statement: A.H. is a board member of the CWHHE Clinical FM, 294 (94.5%) did not and 17 (5.6%) did have a diagnosis of Commissioning, London; has received consulting fees from the secondary FM—a likely underestimate of the true prevalence. Mean Hypermobility Unit and the Hospital of St John and St Elizabeth; has scores on each of the MDHAQ scales were 1.5–3 fold higher in received Royalties from Hypermobility, Fibromyalgia and Chronic Pain patients with secondary FM versus no FM (Table 1). DOCGL was and Churchill Livingston; has received payment for Masterclass highest in patients with secondary FM compared with those with no Training in Hypermobility Syndromes; and has received research FM, while DOCINF and DOCDAM did not differ significantly in the two grants from the National Lottery, volunteer training and HMSA. All groups (Table 1). Mean DOCNON was 5.4 in patients with FM, versus other authors have declared no conflicts of interest. 1.3 in those with no FM, a 4-fold difference. Conclusion: Simple patient and physician questionnaires can provide useful clues to recognize secondary FM in patients with other primary E82. DEVELOPMENT OF A TECHNIQUE TO IDENTIFY rheumatic diagnoses. STAPHYLOCOCCAL ENTEROTOXIN FRAGMENTS IN URINE Disclosure statement: The authors have declared no conflicts of FROM PATIENTS WITH RHEUMATOID ARTHRITIS interest. Laura E. Grace1, Marwan A. S. Bukhari2, Robert M. Lauder3 and Adam M. Taylor1 1Lancaster Medical School, Lancaster University, 2Rheumatology, 3 E80 TABLE 1. Mean MDHAQ scores in patients with various primary rheumatic Royal Lancaster Infirmary and Division of Biomedical and Life diagnoses and a secondary diagnosis of FM Sciences, Lancaster University, Lancaster, UK Non-secondary Secondary P-value FM FM Background: Bacterial toxins are well known to cause a variety of Patients, n (%) 294 (94.5%) 17 (5.6%) infections and diseases, which can lead to toxic shock and sepsis. A Patient measures, mean (S.D.) link has been proposed between pathogenic microorganisms and the MDHAQ-function (FN) (0–10) 2.2 (2.0) 4.0 (1.8) <0.001 development of chronic, autoimmune conditions like the immune MDHAQ-pain (PN) (0–10) 4.8 (3.3) 7.8 (1.4) <0.001 complex disease, RA. Potential pathogenic mechanisms include the DMHAQ-Patient Global (PATGL) (0–10) 4.3 (3.2) 7.3 (1.3) <0.001 hygiene hypothesis and molecular mimicry. Porphyromonas gingivalis, RAPID3 (0–30) 10.8 (7.6) 19.5 (3.0) <0.001 a periodontal pathogen, has been shown to be able to citrullinate host MDHAQ-fatigue (FT) (0–10) 4.2 (3.2) 7.8 (1.9) <0.001 MDHAQ-number of symptoms (0–60) 9.1 (8.1) 22.5 (8.9) <0.001 and bacterial proteins. This foreign proteolytic processing and post- Doctor measures translational modification produces epitopes to which the body has no RHEUMDOC-overall global (DOCGL) 3.5 (2.1) 4.9 (1.8) 0.01 immunological tolerance. For example, anti-CCP antibodies are RHEUMDOC-inflammation (DOCINF) 1.6 (1.9) 1.3 (1.3) 0.73 present in the majority of RA patients. Staphylococcus aureus has RHEUMDOC-damage (DOCDAM) 2.7 (2.2) 3.0 (2.3) 0.31 also been suggested as a candidate organism that could play a role in RHEUMDOC-neither (DOCNON) 1.3 (2.3) 5.4 (2.9) <0.001 the initiation and development of RA. Our unpublished data have MDHAQ: Multidimensional Health Assessment Questionnaire; RAPID3: Routine suggested that immune complexes are detectable in urine. Therefore, Assessment of Patient Index Data 3; RHEUMDOC: Rheumatology Doctor. a method for the rapid detection of common staphylococcal enterotoxin fragments needs to be developed. The first aim was to enzymatically digest staphylococcal enterotoxins B and C (SEB/SEC), toxic shock syndrome toxin-1 (TSST-1) and alpha haemolysin (AH). E81. HYPERMOBILITY SYNDROME STUDY DAY: AN Secondly, we aimed to validate a method for the rapid identification of EXAMPLE OF BEST PRACTICE toxin peptide fragments by mass spectrometry. Methods: Toxins were dissolved in water and incubated with Celia R. Beynon1, Ceril Rhys-Dillon1 and Alan Hakim2,3 proteolytic enzymes. Optimum temperatures and minimum incubation 1Rheumatology, Royal Glamorgan Hospital, Rhondda Cynon Taff, times for each toxin were confirmed by Coomassie stain, western blot 2Rheumatology, Whipps Cross University Hospital, Barts Health NHS and ELISA. Following the confirmation of digestion, peptides were Trust and 3The Hypermobility Unit, The Hospital of St John and St separated by HPLC and analysed using a Bruker HCT ultra Elizabeth, London, UK electrospray ionization mass spectrometer. Peptide identification was performed using the MASCOT database. Background: We identified a learning need in order to increase Results: Trypsin completely digests SEB and SEC after 4 h of awareness of hypermobility syndrome (HMS) and its management in incubation at 378C. Trypsin alone only partially digests AH, therefore our department. a combination of lysine C (4 h) and trypsin (18 h) is required for Methods: A study day was arranged in January 2014 at the Royal complete digestion. Pepsin successfully digests TSST-1 after 2 h of Glamorgan Hospital. The day was attended by 45 people comprising incubation at 378C. All four staphylococcal enterotoxins have been rheumatology consultants, trainees, specialist nurses, physiothera- correctly and confidently identified by our liquid chromatography mass pists, occupational therapists and podiatrists across the five local spectrometry approach. health boards in South Wales. The morning content was delivered by Conclusion: There is currently no published method for the detection Dr Alan Hakim (Senior Lecturer in Rheumatology), Mrs Rosemary Keer and identification of S. aureus fragments. We have shown sufficient (physiotherapist) and Mrs Donna Wicks (CEO of the Hypermobility digestion of each of the staphylococcal toxins for analysis by mass Syndromes Association). Lectures covered clinical features, manage- spectrometry. The toxins may be broken down in the human body, ment strategies and patient support services. The afternoon session which means that the detection of peptide fragments, rather than featured case presentations of five patients with specific problems whole toxin, may lead to more effective identification of a bacterial relating to HMS. Each patient attended their own presentation and presence. Further to these results, the methodology needs to be E-POSTER ABSTRACTS i201

adapted to detect the staphylococcal peptide fragments in urine. The E84. WOULD YOU LIKE TO BE CALLED DEFORMED? application of mass spectrometry analysis of urine for the detection of 1 2 2 3 toxins is non-intrusive and could be extended to a range of Mark Lloyd , Sidrah Akhtar , Nichola Osborne , Hayley McBain , Paul Reilly4 and Ailsa Bosworth5 autoimmune and inflammatory illness that are known to be caused 1 2 3 by bacteria. Rheumatology, Medicine, Frimley Park Hospital, Frimley, Health Services Research, City University, London, UK, 4Rheumatology, Funding Statement: supported by University Hospitals of Morecambe 5 Bay National Health Service Trust (N.T. and D.B.). Cairns Base Hospital, Cairns, Australia and NRAS, Maidenhead, UK Disclosure statement: The authors have declared no conflicts of interest. Background: Would you like to be called deformed? We [consultant rheumatologist, recent successful preparation for the clinical exam (PACES) candidate, recently qualified foundation doctor E83. DEVELOPMENT OF A JOINT INJECTION/ASPIRATION (FY1), PACES examiner, psychologist and person with RA] wouldn’t. SIMULATION COURSE FOR SPECIALITY TRAINEES IN One of the first concerns of RA patients is often that they will develop RHEUMATOLOGY IN THE YORKSHIRE AND HUMBER deformed hands. This is understandable; as well as the functional DEANERY effects of RA changes there is a known association between Anetha Sabanathan1, Rasha Omer1 and Lisa Dunkley2 appearance and depression in patients with RA. Recent National 1Hull Institute of Learning and Simulation, Hull Royal Infirmary, Hull Rheumatoid Arthritis Society patient surveys suggest significant and 2Rheumatology, Sheffield Teaching Hospital NHS Foundation concerns regarding loss of attractiveness, as well as embarrassment Trust, Sheffield, UK regarding appearance. Why then is the term deformity used so frequently? The answer may lie in health professional training. Because they often have stable signs and are systemically well RA Background: The JRCPTB (Joint Royal Colleges Postgraduate Training Board) Specialty Training curriculum for Rheumatology patients often appear in under- and postgraduate examinations (focus in around 20% of PACES cases), where they may undergo physical and mandates that trainees should be able to: describe and identify the surface anatomy of the musculoskeletal system; and gain compe- verbal examination. These examinations are also designed to test empathy and consultation skills. Ironically, however, candidates are tences in joint and soft tissue injections for hand/wrist, elbow, encouraged to use textbooks which specifically suggest the use of the shoulder, hip, knee and ankle/foot joints. This is usually achieved on an informal basis; however, simulation training can provide a realistic word deformity in the description of rheumatoid hands. Methods: We looked at current medical textbooks and examination learning opportunity to prepare for patient care. We obtained deanery approval and funding, designed and successfully ran a simulation guides. Results: The Oxford handbook of Rheumatology advises readers to note course within the Yorkshire and Humber Deanery to aid trainees in any deformity of digits, the BMJ ABC of Rheumatology describes achieving these competencies. We present our experience and feedback received from our attendees. deformities due to joint erosions. The commonly used At a Glance student text book notes the rheumatoid hand swan neck deformity and the Methods: Our objectives were to provide simulated training in joint injections/aspiration for Rheumatology speciality trainees, and to Masterpass student OSCE guide suggests looking for joint deformity; this is echoed in Essential Notes for Medicine Finals. Two of the most popular demonstrate the surface anatomy of the joints using live examples. To show that simulation can improve trainee confidence in joint Membership of the Royal Colleges of Physicians examination aids injection techniques. Eight rheumatology trainees in their first year, one suggest candidates state that there is a symmetrical deforming arthropathy (Rhyder, 2003) and that there is a deforming polyarthritis rheumatology trainee in the second year and one general practitioner trainee (during their rheumatology rotation) took part in a one day (Hall, 2008). The Oxford Handbook of General Practice refers to joint destruction and deformity. The UK’s biggest selling clinical medicine workshop. Station 1 was a communication station, highlighting potential consenting issues. Five stations were procedural, hand/ textbook (The Oxford Handbook of Medicine) suggests looking for joint damage and deformity and swan neck deformities. The popular Kumar wrist, ankle/foot, knee, elbow and shoulder. Surface anatomy was and Clarke (6th edition) describes unsightly deformity. demonstrated on actors and faculty. Bony models were utilized to aid Conclusion: in anatomy demonstration. Regional joint injection instruction manual In his seminal 1949 Lancet paper Richard Asher listed cruelty as one of the seven sins of medicine ‘where the patient is treated was provided as pre-course material. Evaluations were carried out with pre and post-course questionnaires, using a seven point Likert as if he is unconscious or discussed as if he is already on the necropsy slab’. Calling people deformed because they have the typical hand score. Results: Confidence levels (Table 1) increased significantly in appearances of rheumatoid is at least insensitive and could be viewed performing ankle, acromioclavicular, elbow and epicondyle injections. as cruel. The term should be removed from rheumatology teaching and eventually be associated with negative examination assessment. Based Confidence levels increased nonsignificantly in performing wrist, carpal tunnel, glenohumeral, subacromial and knee injection. on psychological research different terms are used in other conditions, including disfigurement, visible distinction, visible difference and 9/10 of the trainees felt that the session fully met their learning objectives, while 1/10 felt that the session mostly met their learning altered appearance. There are no data in the field of RA hand changes. Further research is needed to determine which phrases can reconcile needs. informative clinical description with patient acceptability. Conclusion: Simulation can be successfully used to improve trainee Disclosure statement: confidence in injection techniques, in particular in those joints which The authors have declared no conflicts of interest. are performed less frequently in practice. Our course has obtained deanery approval and funding and will be run annually. Disclosure statement: The authors have declared no conflicts of E85. DEVELOPING A CLINICAL RESEARCH COMMUNITY interest. FOR PHYSIOTHERAPISTS: THE ANKYLOSING SPONDYLITIS INTEREST GROUP NORTH WEST Jennifer Stockdale1, Jane Martindale2, Rachel Evans3, 4 5 6 E83 TABLE 1. Pre- and post-confidence scores William Gregory , Jenny Ratcliffe and Lynne Goodacre 1Physiotherapy, Blackpool Teaching Hospital NHS Foundation Trust, How confident are you in: Mean Mean P-value Blackpool, 2Physiotherapy, Wrightington, Wigan and Leigh NHS pre- post- 3 confidence confidence Trust, Wigan, Physiotherapy, Southport and Ormskirk NHS Trust, 4 score score Southport, Physiotherapy, Salford Royal NHS Foundation Trust, 5 Your overall ability to perform joint injections 2.70 4.50 0.00 Salford, Physiotherapy, East Cheshire NHS Trust, Macclesfield and 6 Performing wrist (mid/ulnar carpel) injections 2.30 4.10 0.53 Research and Development, NHS Research and Development Performing carpel tunnel injections 2.20 4.10 0.53 North West, Manchester, UK Performing glenohumeral joint injections 3.10 4.30 0.12 Performing acromioclavicular joint injections 2.20 3.90 0.02 Background: The NHS constitution outlines a commitment to the Performing subacromial bursae injections 3.10 4.20 0.16 Performing elbow joint (post) injections 2.50 4.60 0.01 promotion, use and conduct of research to improve patient outcome. Performing lat/med epicondyle injections 2.40 4.50 0.01 Making this a reality when services are under increasing pressure is a Performing knee lat/med joint injections 4.60 5.00 0.53 challenge for many clinicians. Physiotherapists (PTs) in the North West Performing tibiotalar (ankle) joint injections 2.60 4.40 0.01 of England have developed a strong community of practice which Lat: lateral; med: medial. seeks to deliver on this constitutional commitment. i202 E-POSTER ABSTRACTS

Methods: The Ankylosing Spondylitis Special Interest Group North West centres, cross-sectional chest CT can only give a definitive diagnosis (ASSIGnw) is a regional forum for physiotherapists working with people in around 75% of cases and even when a diagnosis is made assessing with AS comprising 60 members from 25 Trusts. The groups’ aim is to the degree of inflammation is challenging—an interesting contrast to develop a strong regional network to inform, promote and share our approach to renal inflammation. We struggle with ANA-positive evidence-based practice, benchmark services and develop research patients with ILD and no other CTD features, usually opting for a trial of capability. ASSIGnw meets three times a year and members undertake immune suppressants if there is suggestion of active lung inflamma- work between meetings. Meetings are co-ordinated and led by a clinical tion. Assessing response is again challenging; lack of disease academic and while some include external speakers the majority are progression may be the only evidence of treatment efficacy. highly interactive meetings with a focus on undertaking clinically oriented Conclusion: The ILD MDT has required significant effort to initiate and projects, sharing experiences and ideas and supporting the implemen- maintain but has been of great value. We have learnt much about one tation of high standards of evidence-based practice. another’s specialties and found the process very supportive. Most Results: Since 2008 ASSIGnw has undertaken a range of projects. It importantly, patients have benefited significantly from a combined organized a two day event bringing together PTs and people with AS review. to explore patient’s approaches to exercise and their information Disclosure statement: The authors have declared no conflicts of needs. This led to the development of the first cross-Trust consensus interest. based, user informed and tailored AS exercise resource. Two practical hydrotherapy workshops have been held and work undertaken to develop a standardized approach to undertaking measurements for E87. TREATMENT OF AN ACUTE GOUT FLARE IN PATIENTS the Bath Ankylosing Metrology Index (BASMI). This led to the design WITH KIDNEY DISEASE: A QUESTIONNAIRE SURVEY and conduct of a study exploring the inter- and intra-observer reliability Gowrie Balasubramaniam1, Michael Almond1, Frances Borg2 and of the BASMI, providing evidence that excellent inter- and intra- Bhaskar Dasgupta2 observer reliability among physiotherapists from different clinical 1Renal Medicine and 2Department of Rheumatology, Southend centres was achievable and that differences in BASMI of 1.0 or less University Hospital, Westcliff-on-Sea, UK are within bounds of error with only changes above these limits being confidently interpreted as true clinical changes. Complementing this Background: Patients with chronic kidney disease (CKD) are at high work a subsequent study undertaken by the group, which explored risk of acute gout attacks and are challenging to treat. These patients normative values for the BASMI, indicated that it is unusual for healthy are excluded from most studies due to the risk of NSAIDS. They also individuals to score zero on the BASMI. This has implications for the have multiple comorbidities such diabetes, heart disease and interpretation of BASMI scores, especially at baseline. Members of the hypertension. There is a lack of guidance on treating these patients, group also worked in collaboration with the National Ankylosing and so we undertook a survey in the Eastern region among Spondylitis Society (NASS) to inform the development of the NASS rheumatologists, nephrologists and general practitioners (GPs). research strategy to identify national research priorities. Methods: We sent out e-mail invitations with a link to rheumatologists Conclusion: The specific clinical focus of activities undertaken by and nephrologists who were part of the East of England network. We ASSIGnw has enabled the group to make a significant contribution to not only their own practice but also the evidence base for the assessment and management of AS. The development of the group E87 TABLE 1. Results of survey into the management of acute gout attack in provides a potential model to inform the development of similar clinical patients with CKD (eGFR <60) research networks. Disclosure statement: J.S. has received research funding from Pfizer. Question Total of 54 responses All other authors have declared no conflicts of interest. What treatment would you 54 responses use to treat a CKD (eGFR <60) patient E86. THE VALUE OF A JOINT RHEUMATOLOGY/ with an acute gout RESPIRATORY INTERSTITIAL LUNG DISEASE MEETING attack? Colchicine 38% (20/53) Mark Lloyd1, Lucy Schomberg2, John Seymour2, 17 low-dose colchicine <2 mg/24 h Jonathan Macintyre2, Stacey Starr2 and Nicholas Hughes3 1 high dose colchicine >2 mg/24 h 1Rheumatology, 2Respiratory Medicine and 3Radiology, Frimley Park 1 until symptomatic with diarrhoea 1 did not specify further Hospital, Frimley, UK Steroids 23% (13/53) 7 i.m. injection Background: Lung disease in rheumatic disorders can be challenging. 4 low-dose Pred < 25 mg Multidisciplinary team (MDT) meetings are commonly used in other 1 high dose Pred > 25 mg specialties and in tertiary rheumatology units but perhaps less 1 responded (20–30 mg) frequently in district general hospital (DGH) settings. We report the Both steroids and colchicine 26% (14/53) 8 Low-dose colchicine and i.m. steroids successful implementation of a rheumatology/respiratory interstitial 3 Low-dose colchicine and Pred < 25 lung disease (ILD) meeting in a DGH, with additional tertiary centre 1 Low-dose colchicine and Pred > 25 mg teleconferencing. 1 i.m. steroids and Pred < 25 mg Methods: A monthly morning 2-h session within the radiology department NSAIDs 2% (1/53) was organized. Clinics were re-arranged to enable attendance. The key Other 11% (6/53)—possibly NSAIDs, either attendees include a radiologist with specific interest in interstitial lung colchicine or Pred depending on disease (ILD) an ILD specialist nurse, a rheumatologist and two or three patient profile and specific eGFR How long would you use 43 Responses (11 skipped) respiratory consultants. A 3 monthly teleconference with a tertiary oral treatment for acute respiratory centre takes place. Case discussions are documented real gout attacks in patients time on a shared drive MS Excel spreadsheet. with CKD? Results: The MDT has been operational for 12 months. 74 patients 42% (18/43) <5 days have been discussed: 53 with primary respiratory conditions, 21 with 46% (20/43) >5 days and <2 weeks primary rheumatological conditions. Rheumatology cases included 7% (3/43) >2 weeks four SLE, three RA, three systemic sclerosis, three ANCA-associated 5% (2/43)—until symptoms subside, until prophylactic treatment established vasculitis and one primary SS. The meetings are always useful. Do you think there is clear 51 Responses (3 skipped) Learning points for the rheumatologist include a better understanding guidance/guidance on of cross-sectional chest imaging and its multiple acronyms, the treating acute gout attacks importance of reflux as an ILD mimic, and the need to address this in patients with CKD? aggressively in patients who may be candidates for lung transplanta- 48/51 No tion (lung transplant is contraindicated in reflux). The MDT gives the 3/51 Yes—BSR guidelines chance of a second look—one CCP, RF-positive patient with recent Do you use criteria for the 48 Responses (6 skipped) diagnosis of an acute biopsy proven sarcoid has had several years of treatment for RA and gout attack? associated ILD, which in retrospect was sarcoid ILD. The MDT pushes Yes 9 us to look harder for relevant antibodies—a third set of ENAs sent to a 2 ACR tertiary centre eventually picked up an anti-Zo synthetase antibody in a 1 BSR patient with myositis and aggressive ILD. He has responded well so far 1 gout crystals to rituximab. A further level of support is given by the tertiary centre No 39 teleconference review, both in diagnosis and in support for BSR: British Society of Rheumatology; CKD: chronic kidney disease; eGFR: inspiratory flow rate drugs. Uncertainties remain—even in tertiary estimated glomerular filtration rate; Pred: prednisolone. E-POSTER ABSTRACTS i203

also send out invitations to local GPs who attended for hospital 1Rheumatology, Royal Blackburn Hospital, Blackburn, 2School of update. We used a free online survey website, SurveyMonkey. Health, 3School of Psychology, University of Central Lancashire, Results: There were 54 respondents in total: 24 rheumatologists, 11 Preston, 4Rheumatology, Queen’s Medical Centre, Nottingham, nephrologists and 19 general practitioners. 51/54 (94%) did not feel 5Centre of Rheumatology Research, University College London, that there were clear guidelines to manage acute gout in CKD. This is London, 6Rheumatology, Doncaster Royal Infirmary, Doncaster, reflected in the wide range of responses seen in answer to questions 7Rheumatology, Royal Hallamshire Hospital, Sheffield, 8Peter regarding clinical practice (Table 1). Maddison Rheumatology Centre, Llandudno Hospital, Llandudno, Conclusion: There is a general consensus across all specialities that 9The Kellgren Centre for Rheumatology, Manchester Royal Infirmary, treatment of acute gout in patients with CKD lacks clear guidance. Manchester and 10Rheumatology Research Group, University of Colchicine and steroids (particularly by intramuscular route) appear to Birmingham, Birmingham, UK be favoured. The use of colchicine is limited by the risk of accumulation and increased adverse events, especially in prolonged Background: With improving survival in SLE patients, patient-reported treatment. There is an opportunity for better and safer management health-related quality of life (HRQoL) has become an important such as IL-1 blockade in acute gout associated with renal impairment. outcome. The LupusQoL is a disease-specific patient-derived Disclosure statement: The authors have declared no conflicts of HRQoL measure with good psychometric properties. The aim of the interest. UK multicentre LupusQoL Sensitivity Study was to assess whether LupusQoL is sensitive to change when patients report their change in health status using the global change score (Juniper scale). E88. A PSEUDOSWELLING: WHEN THE PATIENT MOANS Methods: Patients with SLE (4 1997 ACR criteria), experiencing a ABOUT PSEUDOGOUT flare (new A or B by the BILAG-2004 Index) and requiring an increase in Maria Mouyis1, Jessica Manson1 and Mike Brown2 treatment (either prednisolone 20 mg daily, introduction of MTX, 1Rheumatology Department and 2Infectious Diseases Department, parenteral steroids, CYC and/or biologics) were recruited from 9 UK centres. Assessments were undertaken at baseline and monthly for 9 University College London Hospital, London, UK months after initiation of therapy and included the BILAG-2004 disease activity index and the LupusQoL. The LupusQoL has eight domains: Background: An 88 year old male patient with known hypertension, physical health (PH), pain (Pa), planning (Pl), intimate relationships (IR), benign prostatic hyperplasia and pseudogout presented to the private burden to others (BtO), emotional health (EH), body image (BI) and sector with a flare of pseudogout. His knee was injected with fatigue (F). The scores for each domain ranged from 0 (worst health) to methylprednisone. Two weeks later, he presented to the NHS 100 (best health). Patients also completed the global change score, the Rheumatology Clinic with ongoing swelling and pain of the right Juniper scale which ranged from þ7 (improvement) to -7 (deterioration) knee and right ankle. The right knee was warm, swollen and tender for each of the domains of the LupusQoL. The change in the LupusQoL with evidence of a joint effusion. Apart from a low-grade temperature scores when patients reported an improvement in the global score (þ2 of 37.88C, the patient felt well. to þ7), no change in global score (–1, 0, þ1) or a deterioration of the Methods: The patient was treated for a flare of pseudogout with global score (–2 to –7) between consecutive time points are reported colchicine, the pain improved but the knee remained swollen. as mean changes, with 95% CIs constructed using robust standard Repeated fluid aspirations were performed and flucloxacillin was errors to account for repeated patient assessments. started empirically Results: Mean (S.D.) age was 40.9 (12.8) and duration since diagnosis Results: Test results were white cell count 8.43 109/l, neutrophils was 9.3 (8.1) years for the 101 patients recruited; 94% females, 62.6% 6.93 109/l, haemoglobin 13.1 g/dl, platelets 502 109/l, urea and white Caucasians, 15.2% south Asians, 8.1% black Caribbean, 4% electrolytes normal, GFR >90 ml/min, ALP 542 IU/l, alanine transami- black Africans, 5% mixed and 1% Chinese. For all domains of the nase 92 IU/l, urate190 mmol/l and CRP 266 mg/l. First fluid aspirate of LupusQoL, HRQoL [mean (CI)] worsened when patients reported a the right knee: no crystals seen, no organisms seen and Pseudomonas deterioration in health status: PH –3.7 (–5.2, –2.1), Pa –6.5 (–8.9, –4.1), aeruginosa culture growth within 24 h. A second aspirate of the right Pl-4.6 (–7.0, –2.2), IR-7.7 (–14.7, –0.6), BtO –4.6 (–6.9, –2.3), EH–4.4 (– knee (4 days later) showed intracellular CPPD crystals. Urine and 6.0, –2.7), BI –2.5 (–4.2, –0.8) and F ¼ –4.6 (–6.5, –2.8). HRQoL blood cultures were negative. US of the liver was normal. An X-ray of improved in all domains of the LupusQoL when patients reported an the knee showed destruction of the fibular head, involving the proximal improvement in health status: PH 5.6 (4.2, 7.1), Pa 9.3 (7.1, 11.5), Pl 6.3 tibiofibular joint. There was marked periostitis and soft tissue swelling. (3.9, 8.8), IR 8.3 (4.3, 12.4), BtO 10.4 (7.7, 13.1), EH 6.2 (4.7, 7.8), BI 6.4 MRI of the knee showed a very large effusion in the knee. The proximal (3.6, 9.2) and F 8.9 (6.8, 11.0). HRQoL was stable when patients tibiofibular joint was very abnormal. There were erosions and marked reported little change in health status (þ0.6 PH, þ2.5 for BtO). synovitis of the joint but also gross bone marrow oedema of the fibula Conclusion: Using patient reported global change score (Juniper and, to a lesser extent the tibial joint margins. The appearances were scale), all domains of the LupusQoL appear to be sensitive to change consistent with septic arthritis of the joint with associated osteomye- (responsive) when patients report a deterioration or improvement in litis. Flucloxacillin was changed to tazobactam and piperacillin their health status. (Tazocin) based on fluid culture results and sensitivities. While on Disclosure statement: K.M. has received research funding from antibiotic therapy, the patient was also treated with colchicine to treat Arthritis Research UK. All other authors have declared no conflicts of the pseudogout. After day 17, the patient developed an allergic interest. reaction to Tazocin and ciprofloxacin was initiated. By this stage the knee swelling and pain improved and CRP had normalized; the patient was discharged to the community for rehabilitation. Conclusion: No source of the pseudomonal infection was identified. Pseudomonal infections tend to be more common in immune- E90. ABSTRACT WITHDRAWN compromised hosts, but although our patient was elderly he was not immune-compromised. Pseudomonas is associated with prosthetic joint infections rather than native joint infections but has been E91. ABSTRACT WITHDRAWN recognized as an infective organism in patients with RA due to pre- existing damage in the joint. There is very little literature on pseudomonal infections in the presence of pseudogout which is what makes this case unusual. This case also stresses the need to E92. ASSESSMENT OF PHYSICAL ACTIVITY AMONG PATIENTS repeat aspirations and culture in patients with known crystal arthritis— WITH SYSTEMIC LUPUS ERYTHEMATOSUS infection and crystal arthropathy can coexist. Nikolas Malliotis1, Faye Dannhauser2 and Dev Pyne1 Disclosure statement: The authors have declared no conflicts of 1 interest. Rheumatology, Barts and the London NHS Trust, London and 2General Practice, Chigwell Medical Practice, Essex, UK

E89. THE DISEASE-SPECIFIC LUPUSQOL IS SENSITIVE TO Background: The benefits of physical activity are well established for CHANGE IN PATIENTS WITH MODERATE OR SEVERE well-being. There is substantial evidence on the associations between SYSTEMIC LUPUS ERYTHEMATOSUS AFTER TREATMENT OF low levels of physical activity (PA) and increased risk of cardiovascular A FLARE disease (CVD). Patients with SLE have at least twice the CVD risk compared with the general population and PA may have a positive Kathleen McElhone1, Chris Sutton2, Janice Abbott3, Jane Burnell2, impact on this risk. We therefore undertook to assess the PA levels of Peter Lanyon4, Anisur Rahman5, Chee-Seng Yee6, Mohammed Akil7, lupus patients from a large teaching hospital cohort and compared Yasmeen Ahmad8, Ian Bruce9, Caroline Gordon10 and them with the PA levels of patients from the primary care setting Lee-Suan Teh1 without a diagnosis of SLE. i204 E-POSTER ABSTRACTS

Methods: The General Practice Physical Activity Questionnaire E94 TABLE 1 Demographics (GPPAQ) was used to assess the level of PA. This questionnaire is a Demographic Number of patients screening tool validated to measure the PA levels of patients aged 16– Sex Male 10 74 years and can be used both in the primary care and disease- Female 90 specific clinics. A total of 100 patients with a known diagnosis of SLE Age, years <30 7 who attended the Lupus Clinic at Barts Health NHS Trust completed 30–39 22 the GPPAQ. As a comparative group, 100 patients aged 30–50 years 40–49 27 without SLE also completed the GPPAQ while attending a GP surgery. 50–59 19 Their specific diagnoses were not recorded. In both groups, the 60–69 18 GPPAQ generated the Physical Activity Index (PAI), which classifies 70–79 7 Ethnicity White 71 (68% vitamin D level <50 nmol/l) the patients into four different levels of PA: active, moderately active, British 21 (71% vitamin D level <50 nmol/l) moderately inactive and inactive. The recommendations are that all Asian 8 (75% vitamin D level <50 nmol/l) patients who receive a score of less than active should be offered Black — intervention in PA in line with the NICE Physical Activity Guidance (May Treatment HCQ 17 (92% vitamin D level <50 nmol/l) 2013). DMARDs 9 (80% vitamin D level <50 nmol/l) Results: 56% (n ¼ 56) of the SLE patients were found to be inactive Steroids 9 (71% vitamin D Level <50 nmol/l) compared with 46% (n ¼ 46) in the non-SLE group. The number of Combination 54 (57% vitamin D level <50 nmol/l) (DMARDs/HCQ active patients was more than double in the non-SLE compared with plus steroids) the SLE group (37% vs 18%). The number of patients who were less None 11 (73% vitamin D level <50 nmol/l) than active (with a PAI of moderately active, moderately inactive and inactive) and hence in need of PA interventions, was 82% in the SLE group and 63% in the non-SLE primary care group. The differences in these patients had further high dose treatment with the rest continuing PAI between the two groups were found to be statistically significant maintenance therapy alone. after analysis with chi-square (P ¼ 0.0097). Conclusion: This study highlights high prevalence of vitamin D Conclusion: Our SLE patients were found to have statistically deficiency in this SLE population with significant proportions needing significant lower PA levels compared with similar aged patients in long-term maintenance to maintain vitamin D-replete status. Low-dose the community. The need for interventions is particularly high, with vitamin D replacement (up to 800 units of vitamin D) is not always more than 80% of the SLE patients being at a suboptimal PA level. sufficient for maintaining normal vitamin D levels in these patients. Clinicians should therefore consider promoting exercise, referring to Disclosure statement: The authors have declared no conflicts of the current UK Department of Health PA recommendations and NICE interest. guidance on physical activity. Disclosure statement: The authors have declared no conflicts of interest. E95. AN UNUSUAL CAUSE OF PANCYTOPENIA IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOUS Azeem Ahmed1, Jasroop Chana1, Jeremy McNally1 and E93. ABSTRACT WITHDRAWN Rebecca Sampson2 1Rheumatology and 2Haematology, Royal Berkshire Hospital, Reading, UK E94. VITAMIN D DEFICIENCY IN SLE PATIENTS ATTENDING THE CTD CLINIC IN COVENTRY Background: A 40 year old Croatian female presented to our department with a flare of her lupus arthritis in May 2014. She had a James Miller1, Shirish Dubey1 and Maggie Allen1 background of SLE since 2010, with an antibody profile of ANA 1/640 1Rheumatology, University Hospitals Coventry & Warwickshire, (homogeneous), dsDNA 93 and anti-Ro antibody positive. She had Coventry, UK been stable on HCQ 400 mg daily up until this presentation. Methods: Along with a florid peripheral arthritis, she had evidence of Background: Sun exposure is important to maintain adequate levels 3þ blood and 2þ protein in her urine with a stable creatinine level of 49 of vitamin D. This is a challenge for patients with SLE given the majority mmol/l. Her dsDNA rose to 500, correlating with her disease activity. In of patients have photosensitivity. A number of studies have suggested addition, she developed a pancytopenia with haemoglobin 113 g/dl, an association between low vitamin D levels and increased disease white blood cells 2.10 109, neutrophils 1.2 109 and platelets activity but other studies have not corroborated this. A recent review 82 109/l. She was started on a reducing course of prednisolone article has concluded there is no strong evidence to suggest there is 40 mg daily and MMF titrated to 1 g twice daily with normalization of improvement in clinical symptoms following supplementation but there her full blood count. Viral serology indicated previous infection with are very few data from the UK. There is no consensus on optimal parvovirus. In addition she was IgM and IgG positive for CMV for which supplementation making management unclear, although most physi- she was commenced on anti-viral therapy. In July 2014, her cians would tend to treat existing vitamin D deficiency. We therefore pancytopenia recurred despite MMF 1 g twice daily, HCQ 400 mg performed this study to look at our own cohort to investigate the daily and prednisolone 10 mg daily. An abdominal US revealed an prevalence of vitamin D deficiency and assess what treatment options enlarged spleen of 17.3 cm. Despite discontinuing MMF her pancyto- had been effective at maintaining vitamin D-replete status. penia worsened: haemoglobin 98 g/dl, white blood cells 0.8 109 and Methods: We retrospectively looked at all patients attending the platelets 21 109/l. She had a normal ferritin, ESR, CRP, lactate connective tissue disorder clinic at University Hospitals Coventry & dehydrogenase, Vitamin B12, folate and complement levels. The direct Warwickshire from March to August 2014. Only patients with a clinical antiglobulin test was weakly positive and prednisolone was increased diagnosis of SLE were included. This study was approved by the local to 60 mg daily. Initial impression was of increased lupus activity, but research and development department. We recruited 100 patients despite 1 mg/kg prednisolone her platelets continued to fall to obtaining blood results, demographics and prescriptions from our 15 109/l. Following IVIG 2 g/kg, her platelet count only improved to electronic notes system (CRRS). Data were analysed using MS Excel. 40 109/l. Results: 100 patients were included, although 16 patients had not had Results: The patient underwent a bone marrow biopsy in September vitamin D levels tested. The demographics are shown below (Table 1). demonstrating a dry hypocellular aspirate, but the trephine revealed a 84 patients had vitamin D levels tested during their time in clinic. 26 grossly disorganized marrow with increased megakaryocytes with had vitamin D insufficiency (30–50 nmol/l) and 31 had deficiency some clustering. Fibrin grade was 1. The findings were consistent with (<30 nmol/l) with a mean value of 28 nmol/l. 27 patients had normal prefibrotic myelofibrosis. She is currently under assessment for levels; of these 17 were already on maintenance therapy. This level of transplantation due to refractory disease. Full cytogenetics including low vitamin D is comparable to data collected previously on high risk JAK2 mutation screening is pending at time of writing the abstract. populations within the hospital trust in 2013. High dose vitamin D Conclusion: Peripheral cytopenias occur commonly in SLE affecting treatment with ergocalciferol or cholecalciferol (total dose 400 000 80% of patients but can be challenging to diagnose and treat. Case units to 720 000 units) was given to 23 patients, 21 with deficiency and reports reveal myelofibrosis as a cause of pancytopenia in SLE up to 2 with insufficiency. 18 then continued on a maintenance therapy 5%. Other causes of bone marrow abnormalities include aplastic (Adcal D3, Calcichew D3 or Fultium D3). Of the 34 patients not anaemia and pure red cell aplasia, indicating that the bone marrow receiving high dose therapy, 26 were started on maintenance therapy. itself is a target organ in the disease, although the pathogenesis is 8 patients received no treatment. 43 of the 57 patients had a repeat incompletely understood. There is evidence that treating with test performed following treatment and for 36 patients, levels had immunosuppression can cause regression of marrow fibrosis and normalized. Of these 36 patients 27 had their level rechecked regeneration with normal tissue. What is unusual in our patient is her subsequently and 16 had dropped again below 50 nmol/l. Two of pancytopenia did not improve with high dose CS, IVIG or MMF. The E-POSTER ABSTRACTS i205

pathology was only highlighted following the bone marrow biopsy, an male diagnosed with PAN in 2012 following recurrent admissions investigation to consider in resistant cases. with thrombophlebitis, livedo reticularis and weight loss. Skin biopsy Disclosure statement: The authors have declared no conflicts of was in keeping with cutaneous PAN. Disease control was achieved interest. with the use of high dose steroids, MMF and CYC, but was complicated by iatrogenic osteoporosis with recurrent vertebral collapse; DXA showed a Z-score of –4.7 at the lumbar spine and – E96. INTRAVENOUS IMMUNOGLOBULIN IN REFRACTORY 2.7 at the hip despite bisphosphonates and cholecalciferol. Steroid POLYARTERITIS NODOSA weaning resulted in flares of cutaneous PAN. He was treated with Nikita Arumalla1, Animesh Singh2 and Richard Stratton3 Kiovig, with resolution of cutaneous symptoms and fall in CRP from 1A&E, Watford General Hospital, Watford, 2Rheumatology, 118 mg/l to 4 mg/l. At 4 months follow-up, there was continued Charing Cross Hospital and 3Rheumatology, Royal Free Hospital, symptom resolution, oral prednisolone weaned from 35 mg daily to London, UK 15 mg, no further fractures. Conclusion: We have described two cases of PAN refractory to Background: PAN, a vasculitis characterized by necrotic inflamma- conventional treatment with steroids, MMF and CYC that have been tory lesions of the small and medium-sized arteries with extensive successfully treated with IVIG. The mode of action of IVIG in PAN has systemic involvement is conventionally treated with CSs, disease- not been widely studied but probably involves both Fc-dependent and modifying agents and CYC in life-threatening or steroid-refractory (Ab)2-dependent mechanisms of action. IVIG interacts with various disease. The role of IVIG has been described in other inflammatory components of the immune system including an anti-idiotype effect rheumatic conditions such as myositis, although use in PAN is against pathogenic autoantibodies, inhibition of cytokines, saturation limited. of Fc receptors on effector cells of the immune system (B and T Methods: We describe two cases of refractory PAN treated success- lymphocytes, dendritic cells) and regulates a range of genes. With a fully with IVIG at a dose of 2 g/kg over 3 days on a 4-weekly basis. Both lack of controlled studies, the indications of IVIG in vasculitis are patients fulfilled ACR diagnostic criteria for PAN. restricted to those resistant to CSs and immunosuppressive therapy Results: In case 1, a 32-year-old female diagnosed with PAN in and further work is required to establish appropriate treatment 2005, complicated by small bowel ischaemia requiring resection and protocols. bilateral renal artery aneurysms requiring stenting. Initial symptoms Disclosure statement: The authors have declared no conflicts of of abdominal pain, weight loss and fevers persisted with a raised interest. CRP of 122 mg/l despite treatment with i.v. methylprednisolone, MMF and i.v. CYC. Treatment with Privigen led to a dramatic E97. ABSTRACT WITHDRAWN improvement and symptom resolution with a reduction in CRP to 8 mg/l by day 5. Four-month follow-up recorded six cycles of IVIG, ongoing symptom resolution, CRP <5 mg/l, oral prednisolone weaned from 30 mg daily to 12.5 mg. In case 2, a 30-year-old E98. ABSTRACT WITHDRAWN Abstract Reviewers

The Heberden Committee was expanded substantially for the purposes of abstract assessment to ensure that every abstract was peer reviewed, blind, by at least three reviewers. The Heberden Committee is extremely grateful for the assistance of everyone who gave up their time to review abstracts and acknowledges them accordingly:

Heberden Committee Prof Simon Bowman Dr Mwidimi Ndosi Dr Hector Chinoy Dr Elena Nikiphorou Prof Ian Clark Dr Elizabeth Price Prof Christopher Denton Dr Edward Roddy Dr Caroline Flurey Dr Maliha Shakih Dr Patrick Gordon Dr Nick Shenker Dr Zunaid Karim Prof Jaap van Laar Prof Gary MacFarlane Dr David Walker Prof Justin Mason Dr Karen Walker-Bone Prof Robert Moots Prof Gerry Wilson Dr Chetan Mukhtyar Dr Chee-Seng Yee

Additional reviewers Prof David Abraham Dr Celia Gregson Dr Voon Ong Assoc Prof Jo Adams Prof Alison Hammond Dr Ben Parker Dr Yasmeen Ahmad Dr Inam Haq Prof George Peat Dr Nicole Amft Prof Elaine Hay Prof Constantino Pitzalis Dr Marina Anderson Dr Philip Helliwell Dr Mark Porcheret Dr Jacqueline Andrews Prof Ariane Herrick Dr Blandine Poulet Prof Nigel Arden Dr Sam Hider Dr Elizabeth Rankin Dr Eileen Baildem Dr Alan Holmes Dr Karim Raza Ms Cathy Ball Dr Tim Holt Prof Anthony Redmond Dr Francesca Barone Dr Neil Hopkinson Dr Ben Rhodes Prof Anne Barton Dr Kimme Hyrich Dr Ruth Richmond Prof Michael Beresford Dr John Ioannou Dr Sarah Ryan Dr Rupa Bessant Prof John Isaacs Dr Alan Salama Dr Fraser Birrell Prof David Jayne Dr Benjamin Schreiber Prof Marina Botto Dr Paresh Jobanputra Prof David L. Scott Dr Cathy Bowen Dr Gareth Jones Ms Ruth Squires Dr Matt Brown Dr Jeremy Jones Dr Rebecca Stack Prof Ian Bruce Dr Kelsey Jordan Dr Nurhan Sutcliffe Dr Maya Buch Dr Sabrina Kapoor Prof Deborah Symmons Prof Christopher Buckley Dr Lesley Kay Dr Martin Thomas Prof Kuntal Chakravarty Dr Andrew Keat Prof Jonathan Tobias Prof Ernest Choy Dr Clive Kelly Prof Tonia Vincent Dr David Collins Dr Patrick Kiely Dr Nicola Walsh Prof Philip Conaghan Dr Anne Kinderlerer Dr Louise Warburton Prof Andy Cope Dr George Kitas Dr Fiona Watt Dr Fiona Cramp Dr Helen Lachmann Dr Richard Watts Dr Lorraine Croot Dr Peter Lanyon Prof Lucy Wedderburn Prof Bhaskar Dasgupta Dr Thomas Lawson Dr Andrew Whallet Dr Joel David Dr Jo Ledingham Dr Ross Wilkie Dr Julie Dawson Dr Heidi Lempp Dr Anita Williams Dr Chris Deighton Prof Alex MacGregor Dr Lyn Williamson Dr Emma Derrett-Smith Dr Michelle Marshall Dr Elspeth Wise Dr Emma Dures Dr John McBeth Prof Jim Woodburn Prof Michael Ehrenstein Prof Iain McInnes Prof Jane Worthington Prof Paul Emery Dr Hoda Mirjafari Prof Adam Young Dr Cristina Estrach Ms Janice Mooney Dr Dahai Yu Prof Helen Foster Prof Ann Morgan Dr Emmanuel George Prof Wan-Fai Ng Author Index

Numbers refer to page number (abstract number)

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F., i96, (115) Borukhson, L., i176, (E05) Canhao, H., i25, (O07), i89, (099) Akram, Q., i178, (E11) Barkham, N., i57, (022) Bosworth, A., i21, (I119), i62, Cantagrel, A., i71, (058) Alachkar, M., i87, (095) Barnabe, C., i86, (091) (035), i145, (247), i189, (E45), Caporali, R., i188, (E42) Al-Allaf, W., i76, (067) Barnes, T., i58, (024) i201, (E84) Cardy, C., i33, (O20) Alderdice, D., i55, (015) Barone, F., i132, (216) Bouraoui, A., i199, (E79) Carlucci, F., i119, (179) Alenius, G.-M., i48, (O53) Barton, A., i22, (O01), i27, (O10), Bourke, L., i42, (O41) Carpenter, L., i24, (O05), i82, Alexander, Y., i91, (105) i27, (O11), i47, (O49), i48, Bourke, S., i151, (261) (081) Algeo, N., i105, (141) (O53), i61, (034), i70, (054), Bowen, C., i37, (O30) Carrasco, R., i5, (I30), i153, (267) Ali, A. A. 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M., i6, (I31), i65, (042) Bradley, R., i38, (O32) i66, (045), i112, (159) Ambler, N., i35, (O25) Beaton, D., i62, (035) Brennan, F., i41, (O38) Cassell, J., i10, (I47) Amjadi, P., i41, (O38) Bedson, J., i158, (278) Brode, S., i142, (236) Castagno, S., i193, (E60), i199, Ammori, M., i105, (140) Behrens, F., i48, (O53) Bromilow, L., i104, (139), i105, (E77) Anderson, A. E., i70, (054) Behrouzi, R., i106, (143) (140) Castrejon, I., i84, (088), i120, Anderson, E., i126, (199) Beirne, P., i86, (092) Brown, E. B., i71, (057) (182), i121, (183), i139, (232), Anderson, J., i61, (034), i76, (066), Belch, J. JF., i87, (094) Brown, G. M. A., i96, (116) i199, (E80) i80, (077) Belcher, J., i38, (O31) Brown, M. A., i48, (O53) Cates, M. J., i50, (003) Anderson, M., i13, (I69), i34, Bell, J., i33, (O21) Brown, M., i203, (E88) Chaabo, K., i82, (082) (O22) Bell, J., i149, (256), i150, (258) Brown, P., i70, (054) Chalder, T., i83, (085), i84, (087) Andrea Nelson, E., i98, (120) Benger, J., i38, (O32) Bruce, E. S., i59, (028) Chan, J., i140, (234) Andrews, J., i131, (213) Bennell, K. L., i112, (159) Bruce, E., i56, (019) Chan, M., i58, (024), i192, (E54) Andrews, S., i148, (253) Bennett, A. N., i134, (219) Bruce, I. N., i30, (O14), i30, (O15), Chana, J., i128, (203), i204, (E95) Anuj, S., i64, (040), i64, (041) Bennett, A., i10, (I50) i48, (O53), i64, (040), i64, Chandratre, P., i68, (051) Anwar, S., i192, (E53) Bennett, M. J., i71, (058) (041) Chang, S., i80, (076) Arat, S., i111, (156) Bensen, W. G., i77, (069), i186, Bruce, I., i27, (O10), i54, (013), Charlton, J., i61, (032) Arden, N. K., i117, (173), i118, (E37) i56, (019), i58, (024), i91, Chartier, M., i77, (069), i186, (E37) (176) Benveniste, O., i47, (O50) (105), i106, (143), i163, (291), Chatterjea, R., i72, (059) Arden, N., i67, (047), i106, (145), Beresford, M. W., i30, (O15), i156, i163, (292), i177, (E08), i203, Chattopadhyay, C., i197, (E71) i171, (314) (274) (E89) Chau, I., i133, (218) Arkell, P., i128, (202), i189, (E46) Berks, M., i34, (O22) Bruni, C., i60, (029) Chechik, O., i196, (E68) Armitage, J., i87, (094) Bernfeld, B., i196, (E67) Brunner, H. I., i157, (277) Chen, Y., i158, (278) i208 Author Index

Cheng, S., i32, (O17) Critchley, D. J., i108, (149) Dickson, K., i112, (160), i113, Etomi, O., i162, (288) Chesterton, L., i112, (159) Crocker, I., i163, (291), i163, (292) (161) Eusden, J., i49, (O54) Chethan, R., i154, (269) Croft, A. P., i45, (O47) Diffin, J., i26, (O09) Evans, L., i127, (200) Chew-Graham, C., i67, (046) Cronholm, P., i171, (315) Dinsdale, G., i34, (O22) Evans, R., i201, (E85) Chieng, A. S. E., i46, (O48), i153, Culliford, D., i171, (314) Dixey, J., i24, (O05), i90, (101), Evans, S. J., i99, (123), i175, (E03) (267) Cumming, J., i112, (160), i113, i90, (102) Exley, M., i9, (I39) Chinoy, H., i27, (O10), i27, (O11), (161) Dixon, W. G., i16, (I84), i25, (O07), Eyre, S., i48, (O52), i148, (253), i47, (O50), i122, (188), i123, Cummings, S. R., i17, (I88) i27, (O10), i79, (072), i89, i149, (255), i149, (257), i150, (189) Cutolo, M., i34, (O22) (099), i185, (E34) (259) Chitale, A., i56, (020) Cuttell, J., i179, (E16), i180, (E18) Dobrzynska, M. H., i123, (190) Chitale, S., i78, (070), i82, (080), Czirja´ k, L., i188, (E42) Dobson, J., i115, (169) Fagerli, K. M., i134, (220), i135, i92, (107), i139, (231), i145, Dodenhoff, R., i13, (I66) (221) (246) D’Agostino, M. A., i81, (079) Doherty, M., i16, (I83), i64, (039), Fakhreldin, S., i192, (E53) Chowdhury, A. C., i94, (110) D’Angelo, S., i130, (208) i88, (098), i165, (298), i166, Falahee, M., i110, (154) Choy, E., i6, (I31), i145, (246), Dadoun, S., i62, (035) (299) Falk, R., i169, (308) i198, (E76) Dahiya, S., i110, (155) Doherty, S. A., i88, (098) Farrar, J., i171, (315) Christie, D., i155, (273) Danda, D., i122, (187) Donaldson, S. L., i51, (004) Farrell, W. E., i48, (O51) Chudyk, A., i68, (049) Dando, C., i37, (O30) Donnelly, C., i55, (015) Farrow, L., i197, (E72) Chura, R., i115, (169) Danko, K., i47, (O50) Donnelly, S., i133, (218) Fautrel, B., i62, (035) Ciurtin, C., i115, (167), i129, (206), Dannhauser, F., i203, (E92) Donnelly, S., i30, (O13) Feighery, C., i132, (214) i151, (260) Darzi, J., i65, (042) Dooley, M., i111, (158) Feldman, D., i71, (058) Clark, E. M., i60, (030), i128, (204) Das, S., i74, (061) Dore´ , C. J., i74, (062) Feletar, M., i48, (O53) Clarke, B., i168, (304) Dasgupta, B., i32, (O18), i33, Doria, A., i47, (O50) Ferguson, E., i168, (305) Clarke, S., i38, (O32) O19 I63 213 Douglas, K., i182, (E25) Fernando, X., i147, (250) Clarkson, K., i39, (O34), i66, ( ), i12, ( ), i131, ( ), Douglas, M. R., i182, (E25) Ferreira, J. C. F., i74, (061) (045), i68, (050) i171, (314), i173, (318), i202, Dregan, A., i61, (032) Filer, A., i33, (O20), i33, (O21), i42, Clarson, L. E., i38, (O31) (E87) Drew, S., i106, (145) (O40), i69, (052) Clayton, A. M., i100, (125) Daskin, J., i132, (216) Dreyer, L., i25, (O07), i89, (099) Filkova, M., i185, (E35) Clayton, R., i78, (070) Dass, S., i12, (I61), i86, (092) Druce, K. L., i26, (O08) Fina-Aviles, F., i67, (047) Clewes, A. R., i100, (125) Datta, P., i140, (233) Druett, K., i107, (146) Finckh, A., i25, (O07), i89, (099) Clinch, J., i11, (I55), i18, (I93) Davenport, G., i64, (039), i165, Dubey, S., i51, (005), i78, (071), Finney, A., i67, (046) Clubbs Coldron, B., i75, (064) (298), i166, (299) i175, (E01), i204, (E94) Finney, D., i21, (I117) Clynes, M. A., i183, (E28) David, J., i51, (006), i170, (312) Duda, J., i125, (196) Firth, J., i18, (I94), i107, (147) Clynes, M., i63, (036), i63, (038) Davidson, J. E., i153, (267) Duffort, P., i115, (169) Fisher, B., i132, (216), i42, (O40), Coady, D., i131, (213) Davidson, L., i198, (E75) Duffy, H., i68, (049) i69, (052) Cobb, J., i132, (216) Davies, B., i45, (O46) Duffy, S., i109, (151) Fisher, C., i116, (170) Cobb, J., i148, (252) Davies, K., i189, (E44) Dunkley, L., i146, (249), i201, Fisher, C., i45, (O45) Cobine-Davies, M., i51, (004) Davies, L., i5, (I30) (E83) Fitchett, K., i144, (244) Cogollo, E., i122, (186) Davies, R., i153, (266), i153, (267), Durcan, L. J., i87, (096) Fitter, S. L., i96, (116) Cohen, H., i11, (I56) i156, (274), i156, (275) Dures, E., i18, (I95), i35, (O25) FitzClarence, H., i115, (167), i129, Cole, Z., i194, (E61) Davies, R., i103, (135) Dyke, B., i69, (052) (206) Coles, M., i8, (I38) Dawes, P. T., i48, (O51) Dziedzic, K. S., i67, (046), i68, Fitzgerald, D., i160, (285) Collins, D., i121, (185), i147, (251) Dawson, J. K., i77, (068), i100, (049), i127, (201) Fitzgerald, O., i48, (O53) Collins, S., i145, (247) (125) Fitzgerald, P., i98, (120) Collinson, D., i194, (E61) Dawson, J., i171, (315) Fitzmaurice, T. J., i142, (236) Combe, B. G., i28, (O12), i73, Day, N., i97, (119) Earl, A., i98, (121) Fitzpatrick, C., i135, (222) (060) D’Cruz, D., i6, (I33), i9, (I42), i20, Earl, K. E., i43, (O42) Fletcher, C., i195, (E66) Conaghan, P., i1, (I02), i8, (I36), (I110), i30, (O15) i61, (032), Earl, S., i71, (057), i180, (E21) Flurey, C. A., i9, (I44), i36, (O28), i73, (060), i127, (200) i95, (113), i163, (293), i166, Eassa, L., i95, (112) i111, (157) Congdon, R., i183, (E29) (300) Easton, V., i44, (O43) Fonseca, C., i159, (282) Connolly, D., i113, (162), i132, De Benedetti, F., i157, (277) Edwards, C. J., i30, (O15), i34, Forbes-Price, A., i77, (068) (214), i135, (222) De Bleecker, J., i47, (O50) (O24), i67, (047) Ford, G., i20, (I113) consortium, R.-M., i64, (040), i64, De Cock, D., i115, (168) Edwards, C., i94, (111) Fordham, J. N., i83, (083) (041) de Pablo, P., i33, (O21) Edwards, M. H., i61, (033), i63, Forgie, B., i98, (121) Cook, M. J., i26, (O09) de Souza, S., i2, (I12), i65, (042), (036), i63, (038), i124, (192), Forrester-Barker, W., i173, (318) Cook, R. E., i144, (243) i115, (169) i129, (205), i129, (207), i130, Foster, H. E., i45, (O46), i153, Cooper, A., i131, (213) Deakin, C. T., i44, (O44) (208), i130, (209) (267), i156, (274), i157, (276) Cooper, C., i17, (I89), i61, (033), Dean, L. E., i136, (224) Egerton, C., i197, (E72) Foster, N. E., i36, (O27), i40, i63, (036), i63, (038), i66, Deane, K. H. O., i132, (215) Eissa, M., i178, (E12), i192, (E53) (O36), i112, (159), i113, (163), (044), i67, (047), i117, (173), Deary, V., i132, (215) Elbaz, A., i124, (193), i196, (E67), i140, (233) i117, (174), i118, (176), i124, Debi, R., i124, (193), i196, (E67) i196, (E68) France, J., i190, (E47) (192), i129, (205), i129, (207), Dejonckheere, F., i80, (076) Elder, M. J., i142, (236), i143, Francis, I., i122, (187) i130, (208), i130, (209) Denison, H. J., i63, (036) (239) Frane, J., i157, (277) Cooper, N. A., i96, (116) Dennison, E. M., i61, (033), i63, El-Hammady, D. H., i84, (086) Fraser, I., i35, (O25) Cooper, R. G., i31, (O16), i43, (036), i66, (044), i124, (192), Ellis, B., i20, (I111) Fraser, P., i148, (253) (O42), i47, (O50) i129, (205), i129, (207), i130, Ellis, L., i142, (236) Freeston, J. E., i76, (065) Cooper, R., i122, (188) (209), i183, (E28) Ellis, S., i98, (122) Friswell, M., i157, (276) Cooper, V., i67, (046), i68, (049) Denton, C. P., i19, (I103), i32, El-Sherbiny, Y. M., i81, (078), Frith, J., i132, (215) Cope, A. P., i49, (O54), i70, (055) (O17), i60, (029), i101, (128), i164, (295) Fryer, A. A., i48, (O51) Cope, A., i74, (062), i185, (E35) i159, (282), i159, (283), i160, Elwyn, G., i107, (147) Fu, B., i22, (O01), i27, (O11), i47, Cordingley, L., i46, (O48), i61, (284), i161, (287), i162, (288) Emery, P., i23, (O04), i28, (O12), (O49) (034), i154, (268) Derrett-Smith, E., i60, (029), i159, i34, (O24), i54, (012), i73, Fuji, T., i125, (194) Costello, R., i185, (E34) (283), i160, (284) (060), i74, (061), i76, (065), Furst, D. E., i28, (O12), i32, (O17), Cotton, C. V., i43, (O42) 076 Diamantopoulos, A., i80, ( ) i81, (078), i86, (092), i97, i73, (060) Cox, A. J., i100, (125) Diamantopoulos, A., i32, (O18), (117), i97, (118), i131, (213), Cramp, F., i5, (I26), i106, (144), i33, (O19), i173, (318) i164, (295) i109, (152), i109, (153), i188, Diboll, J., i70, (054) Emes, R. D., i48, (O51) Gade, A., i137, (226) (E43) DiCarlo, J. C., i73, (060) Emin, A., i171, (314) Gadsby, K., i10, (I52) Craven, A., i172, (316), i173, (317) DiCicco, M., i93, (109) English, C., i45, (O46) Gaffney, K., i19, (I100), i19, (I104), Crawford, G., i137, (226) Di Cicco, M., i138, (229) Erb, N., i30, (O15) i179, (E15) Cribbs, A., i41, (O38) Dickinson, M., i161, (286) Erwig, L. P., i18, (I98) Gaillez, C., i81, (079) Cristinacce, P., i91, (105) Dickson, C., i105, (141) Estrach, C., i59, (027) Gak, N., i160, (284) Author Index i209

Galavan, N., i132, (214) Griffith, S., i98, (121) Hayes, F., i181, (E24) Humphreys, J. H., i22, (O01), i76, Galeazzi, M., i77, (069), i81, (079), Griffiths, B., i13, (I70), i30, (O15), Hayward, R. J., i136, (223) (066), i148, (254) i186, (E37) i131, (213), i177, (E07) Hayward, R., i158, (278) Hunter, D., i105, (141) Galiutina, O., i167, (301) Griffiths, C. E. M., i27, (O11) Hazell, L., i2, (I13) Hunter, J., i131, (213) Galloway, J., i21, (I118), i65, Grocott, C.-L., i189, (E46) Hazra, N., i61, (032) Hurley, M. V., i6, (I31), i126, (199) (042), i74, (062), i75, (063), Grosart, R., i144, (242), i145, Healey, E. L., i4, (I22), i40, (O36), Hurley, M., i100, (126), i112, i85, (090), i88, (097), i89, (245) i67, (046), i127, (201) (160), i113, (161) (100), i92, (106), i93, (108), Guerra, S. G., i159, (282) Heath, J. J., i179, (E16), i180, Hutchings, A., i32, (O18), i33, i115, (169), i123, (189), i185, Gul, H. L., i23, (O04) (E18) (O19), i171, (314), i173, (318) (E35), i189, (E45) Gullick, N., i65, (042), i88, (097), Hellgren, K., i25, (O07) Hutchinson, C., i14, (I77) Gamal, R. M., i84, (086) i89, (100) Helliwell, P., i1, (I01), i48, (O53), Hutchinson, D., i184, (E32) Garner, R. H. K., i116, (171) Gulliford, M., i61, (032) i147, (250) Hutchinson, J., i60, (030) Garrood, T., i82, (082), i98, (121), Gunawardena, H., i58, (026) Helliwell, T., i168, (306) Hyrich, K. L., i5, (I30), i10, (I49), i151, (262), i158, (279) Gunn, J. L., i51, (006), i52, (007) Helm, E. J., i78, (071) i25, (O07), i27, (O10), i27, Gaskin-Colligan, F., i108, (148) Gunn, J., i170, (312) Helyes, Z., i8, (I34) (O11), i47, (O49), i59, (028), Gasparyan, A., i16, (I85) Gupta, A., i154, (269), i154, (270), Henderson, J.-A., i55, (015) i61, (034), i76, (066), i80, Gebhart, D., i171, (315) i155, (271) Heneghan, C., i38, (O31) (077), i89, (099), i134, (220), Gedalia, A., i157, (277) Gupta, M., i131, (213) Henry, M. T., i160, (285) i135, (221), i149, (255), i153, George, E., i36, (O29) Gupta, N., i122, (187) Hensor, E. M. A., i23, (O04) (266), i153, (267), i154, (268), Georgiou, A., i140, (234), i199, Gurden, S., i10, (I51) Herman, A., i124, (193), i196, i156, (274), i156, (275), i184, (E79) (E68) (E33), i187, (E41) Georgopoulou, S., i75, (063), Herna´ ndez, V., i25, (O07), i89, i189, (E45) Haas, J. P., i148, (252) (099) Iagnocco, A., i81, (079) Gerloni, V., i157, (277) Haase, A., i106, (144) Herrick, A., i9, (I40), i34, (O22), Iannone, F., i25, (O07), i89, (099) Ghio, D., i46, (O48), i154, (268) Hackett, K. L., i132, (215) i161, (286) Iaremenko, K., i170, (311) Ghouma, A., i197, (E73) Hagel, S., i62, (035) Heslop, P., i36, (O29), i108, (148), Iaremenko, O., i170, (311), i190, Ghuman, A. S., i114, (166) Haggett, A., i114, (166) i109, (151) (E48) Giardina, E., i48, (O53) Haigh, R., i71, (057) Hesselstrand, R., i34, (O22) Ibrahim, F., i24, (O06), i74, (062), Gibson, J. H., i130, (210) Haim, A., i196, (E68) Hetland, M., i25, (O07), i89, (099) i92, (106) Gibson, S., i36, (O29) Hakim, A., i4, (I19), i200, (E81) Hewins, P., i162, (290) Ibrahim, I., i148, (254) Gibson, T., i118, (177) Hale, E., i9, (I43) Hewitt, J., i75, (064), i83, (084) Iglarz, M., i159, (283) Gidman, W. K., i5, (I30) Hall, A., i140, (233) Hewlett, S., i35, (O25), i36, (O28), Inanc, M., i162, (289) Gilbane, A., i159, (283) Hall, J., i102, (133) i106, (144), i109, (152), i109, Ioannou, J., i13, (I71) Giles, I. P., i19, (I102), i41, (O39), Hall, S., i71, (058), i133, (217) (153), i188, (E43) Ioannou, Y., i42, (O41), i45, (O45), i101, (129), i104, (138), i131, Hall-Craggs, M., i45, (O45) Heycock, C., i86, (093) i153, (267), i155, (273) (213) Halliday, N., i112, (159) Hider, S. L., i38, (O31), i39, (O34), Iqbal, K., i86, (093) Gillibrand, R., i111, (157) Hameed, B., i151, (261) i66, (045), i68, (050), i152, Irvine, L., i22, (O02) Ginn, K., i12, (I64) Hamilton, J., i86, (093) (263), i168, (306) Irving, K., i83, (085), i158, (279) Gladman, D. D., i133, (217) Hamilton, W., i171, (314) Higgins, J., i194, (E61) Isaacs, J. D., i27, (O11), i47, Glossop, J. R., i48, (O51) Hammam, N., i155, (272) Hill Gaston, J. S., i142, (236), (O49), i69, (053), i70, (054), Glover, A. R., i96, (116) Hammar, F., i69, (052) i143, (239), i143, (240) i149, (255), i187, (E38), i187, Goel, R., i122, (187) Hammer, H. B., i81, (079) Hill, A. C., i99, (123), i175, (E03) (E41) Goff, I., i56, (018) Hammond, A., i3, (I17), i101, Hinamn, R. S., i112, (159) Isenberg, D. A., i1, (I04), i30, Goldsmith, P., i20, (I109) (130), i111, (158), i117, (172), Hinks, A., i148, (252) (O15), i96, (114), i115, (167), Goljanek-Whysall, K., i43, (O42) i121, (184) Hinsch Gylvin, L., i188, (E42) i122, (186), i131, (213), i164, Gomez-Reino, J. J., i133, (217) Hampson, G., i158, (279) Hirsch, G., i125, (196), i126, (197), (294), i164, (296) Gooberman-Hill, R., i38, (O32), Han, B., i47, (O49) i126, (198) Isorna Porto, M. J., i23, (O04) i108, (150), i128, (204) Hancock, T., i145, (245) Ho, P., i48, (O53), i180, (E17) Goodacre, L., i136, (225), i201, Hands, R., i138, (229) Hoare, O., i144, (242) (E85) Hanna, M. G., i47, (O50) Hockings, P., i91, (105) Jacklin, A., i111, (158) Goodall, J. C., i142, (236), i143, Hanns, L., i155, (273) Hofstetter, C., i62, (035) Jacklin, C. B., i145, (247) (239), i143, (240) Hanson, S., i114, (166) Hogan, S. L., i169, (308) Jacklin, C., i144, (244) Goodfield, M., i54, (012) Hansson, M., i110, (154) Holden, M. A., i36, (O27), i40, Jackson, M. J., i31, (O16) Goodheart, A., i54, (013) Haq, I., i92, (106) (O36), i112, (159) Jackson, S., i113, (163), i140, Goodson, N. J., i59, (027), i192, Haraoui, B., i188, (E42) Holden, W., i183, (E29) (233) (E54) Harber, M., i159, (282) Hollick, R. J., i2, (I11) Jacques, T. S., i44, (O44) Gordon, C., i30, (O15), i162, Harding, I., i60, (030) Holmes, A., i159, (283) Jagadeesh, L. Y., i85, (089) (290), i203, (E89) Hargreaves, B., i69, (053), i70, Holmes, C., i117, (174) Jagannath, D., i63, (038) Gordon, F., i98, (122) (054) Holt, T. A., i67, (048) Jahreis, A., i32, (O17) Gordon, J., i77, (068) Harney, S., i160, (285) Holton, J. L., i44, (O44) James, J., i91, (105) Gordon, P., i89, (100), i122, (188), Harper, L., i172, (316) Hong, C., i85, (089), i151, (262) James, K., i131, (213) i123, (189) Harris, C. E., i136, (223) Hope, H. F., i61, (034) Jameson, K. A., i63, (036), i66, Gorodkin, R., i54, (014), i120, Harris, H., i92, (106) Horton, S. C., i76, (065) (044), i129, (207), i130, (209) (181) Harrison, A., i158, (280) Hoschtitzky, A., i54, (014) Jani, M., i27, (O10), i27, (O11) Gottenberg, J.-E., i25, (O07), i89, Harrison, T., i86, (091) Hotopf, M., i84, (087), i88, (097) Jasim, M. A., i76, (067) (099) Harry, D. J., i99, (123) Hough, Y., i100, (125), i111, (158) Javaid, K., i52, (007), i67, (047) Gough, A., i51, (004) Hart, D., i131, (211) Howell, K., i34, (O22) Javaid, M. K., i118, (176) Grace, L. E., i200, (E82) Harty, L., i160, (285) Hu, C., i133, (217) Jayakumar, K., i88, (098), i197, Grace, M., i37, (O30) Harvey, J., i60, (029) Hu, Y., i169, (308) (E73) Graham, K., i38, (O33), i65, (043) Harvey, N. C., i130, (208) Huang, A., i84, (088), i121, (183), Jayne, D., i30, (O15) Grainge, M., i64, (039), i165, Harvey, P. R., i162, (290) i199, (E80) Jayne, M., i172, (316) (298), i166, (299) Haskard, D., i119, (179) Huffmeier, U., i48, (O53) Jefferies, C., i30, (O13) Grant, D., i159, (281) Hassell, A. B., i99, (124), i109, Hughes, L., i100, (126) Jeffery, L. E., i42, (O40) Grant, R., i112, (160), i113, (161) (151), i143, (241) Hughes, N., i202, (E86) Jeffery, R., i183, (E30) Gray, L., i181, (E22) Hatsukami, T., i91, (105) Hughes, R., i68, (049) Jeffries, A. P. D., i89, (100), i92, Grayson, P. C., i173, (317) Hauari, H., i112, (160), i113, (161) Hughes, R., i145, (247) (106) Green, A., i89, (099) Hauser, B., i100, (127) Hui Wong, W., i183, (E28) Jenkins, P., i54, (014) Green, P., i41, (O38) Hawarden, A., i99, (124), i108, (148) Huizinga, T. WJ., i28, (O12), i73, Jerman, E., i44, (O43) Greenwood, R., i38, (O32) Hawley, S. J., i117, (173) (060) Jie, S., i91, (105) Gregersen, P. K., i47, (O50) Haworth, K. E., i48, (O51) Humby, F., i93, (109), i102, (131) Jimmieson, P., i46, (O48) Gregory, B., i41, (O38) Hay, E. M., i13, (I65), i40, (O36), Humphrey, C., i69, (053) Jinks, C., i36, (O27), i67, (046) Gregory, W., i201, (E85) i140, (233) Humphreys, E., i145, (246) Jobanputra, P., i33, (O21) i210 Author Index

Johnstone, E., i163, (291) Kirkham, B., i4, (I20), i82, (082), Lilleker, J. B., i122, (188) Manning, J., i34, (O22), i161, Joly, J., i115, (168) i85, (089), i137, (228), i151, Lim, C. S. E., i179, (E15) (286) Jones, A., i14, (I79) (262) Lim, E. L. P., i180, (E17) Manning, V. L., i6, (I31) Jones, G. T., i26, (O08), i136, Kirwan, J. R., i36, (O28), i109, Lim, K., i116, (171) Manson, J., i129, (206), i151, (224) (152), i109, (153) Lim, V., i87, (095), i145, (246) (260), i203, (E88) Jones, G., i114, (166) Kitas, G. D., i87, (094), i125, (196), Limaye, V., i47, (O50) Mant, T., i185, (E35) Jones, H., i78, (070) i126, (197), i126, (198) Ling, C.-Y., i118, (177) Marianayagam, T., i98, (122) Jones, J. G., i78, (070), i82, (080), Kither, H., i163, (291), i163, (292) Ling, S., i54, (014) Mariette, X., i25, (O07), i89, (099) i144, (243) Klocke, R., i125, (196), i126, Linklater, H., i168, (304) Marion, M. C., i148, (252) Jones, S., i92, (107) (197), i126, (198), i195, (E65), Linton, D., i62, (035) Marks, J., i117, (174) Jones, V., i111, (158) i96, (116) Lip, S., i100, (127) Marques, E., i38, (O32) Jordan, A., i33, (O21), i45, (O47) Knight, L., i110, (155) Lippett, J., i117, (173) Marra, G., i151, (260) Jordan, J., i67, (046) Knight, S., i101, (129) Listing, J., i25, (O07), i89, (099) Marrin, K., i107, (147) Jordan, K., i158, (278) Koduri, G., i77, (068) Little, J., i56, (019) Marshall, D., i36, (O29) Jorgensen, C., i157, (277) Korendowych, E., i48, (O53) Little, M., i18, (I99) Marshall, M., i39, (O35), i88, (098) Juarez, M., i69, (052) Kosashvili, Y., i196, (E67), i196, Litwic, A. E., i61, (033), i63, (036) Marshall, T., i22, (O01), i148, Judge, A., i117, (173), i118, (176), (E68) Litwic, A., i63, (038) (254) i172, (316), i173, (317) Koskela, S., i126, (199) Lloyd, M., i201, (E84), i202, (E86) Marthi, A., i103, (136), i103, (137) Kraus, A., i145, (246) Loader, S., i194, (E61) Martin, D., i15, (I80) Kriss, S., i3, (I14) Lohr, S., i48, (O53) Martin, L., i86, (091) Kaambwa, B., i6, (I31) Kudari, M., i128, (203) Lorente-Canovas, B., i74, (062) Martin, P., i148, (253) Kabia, A. R., i86, (092) Kuet, K.-P., i194, (E62) Lorenz, H.-M., i77, (069), i186, Martin, U., i36, (O29) Kalinowski, M., i36, (O29) Kuhn, I. L., i72, (059) (E37) Martindale, J., i136, (225), i201, Kamali, S., i162, (289) Kulasinghe, M. A. I., i197, (E71) Lostarakos, V., i128, (202) (E85) Kane, D., i48, (O53), i80, (075) Kumar, K., i110, (154) Lovell, D. J., i157, (277) Martini, A., i157, (277) Kaneshiro, S., i125, (194) Kuvikova, I., i167, (301) Luben, R. N., i64, (040), i64, (041) Martins, F., i25, (O07), i89, (099) Kapoor, R., i118, (175) Kyle, S., i119, (178) Ludivico, C., i71, (058) Marzo-Ortega, H., i19, (I101), i48, Karjigi, U., i77, (068) Lundberg, I., i47, (O50) (O53) Karppinen, J., i34, (O23) Lunt, M., i26, (O09), i27, (O10), Mascarenhas, R., i71, (057) Karyekar, C. S., i28, (O12), i73, Lacaille, D., i62, (035) i79, (072), i153, (266), i156, Massey, J., i70, (054) (060) Lador, R., i196, (E68) (275) Matcham, F., i49, (O54), i83, Kasapc¸ opur, O¨ , i162, (289) Lages, A., i60, (029) Luqmani, R. A., i32, (O18), i33, (085), i84, (087), i88, (097) Kasavkar, G., i194, (E63), i198, Laishram, S., i122, (187) (O19), i67, (047), i67, (048), Mathew, A. J., i122, (187) (E74) Lamb, J., i47, (O50), i122, (188) i169, (308), i170, (312), i171, Mathew, R. G., i144, (243) Kassim Javaid, M., i117, (173) Landewe´ , R., i137, (228) (314), i171, (315), i172, (316), Mathialahan, T., i87, (095) Kaur-Papadakis, D., i134, (219) Langefeld, C. D., i148, (252) i173, (317), i173, (318) Mathiesen, P., i47, (O50) Kavanaugh, A., i133, (217), i137, Lanier, G., i171, (315) Lutalo, P. M. K., i30, (O15), i95, Mattey, D. L., i48, (O51) (228) Lanyon, P., i13, (I68), i169, (310), (113), i163, (293) Matucci-Cerinic, M., i60, (029) Kay, L., i136, (224) i173, (318), i203, (E89), i30, Lyn Tan, A., i76, (065) Mauri, C., i14, (I75) Kazmi, M. F., i52, (008), i176, (O15), i64, (039), i131, (213), Lynch, B., i181, (E24) Maxton, C., i179, (E14) (E04) i165, (298), i166, (299), i169, Mazumdar, S., i162, (290) Kearns, G., i30, (O13) (309) Mc Laughlin, M., i72, (059) Kearsley-Fleet, L., i27, (O10), Latham, S., i127, (200) Ma, M., i74, (062) McAlear, C., i171, (315) i59, (028), i153, (266), i156, Lauder, R. M., i200, (E82) Ma, Q., i114, (164) McAllister, K., i48, (O52), i148, (274), i156, (275), i184, Law, R., i139, (231) Maatta, J., i34, (O23) (253) (E33) Lawrence, A., i94, (110), i169, Macfarlane, G. J., i26, (O08), McAlpine, C., i190, (E47) Keat, A. C., i136, (223) (307) i136, (224) McArdle, A., i31, (O16), i43, Keenan, A.-M., i20, (I115) Lawson, T., i146, (248) MacGregor, A. J., i22, (O02), i26, (O42) Kehoe, O., i125, (195) Lazarou, I., i93, (109), i138, (229) (O09), i34, (O23), i38, (O33), McBain, H., i201, (E84) Keidel, S., i97, (117), i97, (118) Le Bars, M., i186, (E37), i77, i44, (O43), i64, (040), i64, McBeth, J., i35, (O26) Kellom, K., i171, (315) (069), i81, (079) (041), i65, (043), i71, (056), McCarthy, E. M., i30, (O13) Kelly, C., i77, (068), i86, (093) Leal, J., i118, (176) i150, (258) McCarthy, G. M., i87, (096) Kelly, S., i190, (E47) Leandro, M., i115, (167) Macintyre, J., i202, (E86) McCormick, J., i42, (O41) Kelly, S., i93, (109), i138, (229) Leask, A., i142, (238) Mackay, K., i94, (111) McDonald, B., i173, (318) Kennedy, A., i41, (O38) Lee, A. T., i47, (O50) Mackenzie-Green, B., i119, (178) McElhone, K., i203, (E89) Kenny, D., i87, (096) Lee, J. J., i78, (071) Mackie, S. L., i51, (004), i168, McErlane, F., i157, (276) Khalifa, H., i84, (086) Lee, S., i80, (075) (305) McGovern, A., i148, (253) Khamashta, M., i30, (O15) Leggett, S. A., i62, (035) Mackworth-Young, C., i119, (179) McHugh McHugh, N., i30, (O15) Khan, A., i181, (E24) Lehner, P. H., i41, (O37) MacMullan, P. A., i87, (096) McHugh, N. J., i44, (O44), i67, Khan, H., i53, (009) Leith, M., i53, (010), i53, (011) MacPhie, E., i184, (E31), i191, (048), i131, (213), i48, (O53) Khan, I., i176, (E05) Lemmey, A. B., i78, (070), i82, (E52), i199, (E78) McInnes, I. B., i42, (O40), i137, Khan, S. Y., i176, (E06) (080), i139, (231), i144, (243) Maddison, P., i78, (070), i82, (080) (228) Khan, S., i180, (E19) Lempp, H., i65, (042), i75, (063), Madigan, A. M., i87, (096) McLaren, J., i131, (213) Khanbhai, T., i151, (261) i108, (149), i115, (169), i189, Magliano, M., i103, (136), i103, McLaughlin, M., i79, (073) Khanna, D., i32, (O17) (E45) (137), i128, (203), i173, (318) McManus, R., i48, (O53) Khaw, K.-T., i64, (040), i64, Lendrem, D., i70, (054), i132, Magliano, M., i102, (133) McNally, E., i32, (O18), i33, (O19) (041) (215) Mahtani, K. R., i67, (048) McNally, J., i204, (E95) Khawaja, A. A., i41, (O39) Lenman, M., i193, (E60), i199, Mahto, A., i93, (109), i138, (229) McPherson, S., i50, (001) Khedr, E. M., i84, (086) (E77) Majeed, S. S., i194, (E64) McQueen, P., i37, (O30) Kiely, P. D. W., i24, (O05), i88, Lenton, D., i100, (125) Makadsi, R., i98, (121) McWilliams, D. F., i88, (098) (098), i90, (101), i90, (102), Lespessailles, E., i133, (217) Maki, D., i108, (149) Md Yusof, Md. Y., i86, (092) i152, (264) Leszczynski, P., i71, (058) Malaiya, R., i168, (304) Mease, P. J., i133, (217), i137, Kilding, R., i194, (E62) Levasseur, K., i126, (198) Mallen, C. D., i38, (O31), i39, (228) Kinder, A., i137, (227) Lewis, C. M., i49, (O54), i70, (055) (O34), i66, (045), i67, (046), Medina Peralta, M., i67, (047) King, J., i114, (165) Lewis, M. J., i41, (O37) i68, (050), i112, (159), i152, Medina-Quin˜ ones, C., i164, (294) King, J., i97, (119) Lewis, M., i112, (159), i140, (233) (263), i168, (306) Mehaney, D., i192, (E53) King, Y., i184, (E33) Lewis-Barned, N., i1, (I07) Malliotis, N., i203, (E92) Mehta, K., i167, (302) Kingsley, G. H., i24, (O06), i85, Lewthwaite, A., i182, (E25) Manhas, R., i119, (178) Mehta, P., i119, (179) (090) Li, C., i102, (132) Mani-Babu, S., i166, (300) Mehta, T., i167, (302) Kingsley, G., i74, (062) Lightfoot, A. P., i31, (O16), i43, Mankia, A. K., i23, (O03) Mellemkjær, L., i25, (O07), i89, Kinsey, K. L., i107, (147) (O42) Mankia, K., i51, (006), i170, (099) Kiran, A., i171, (314) Lightstone, E., i18, (I97) (312) Menz, H. B., i39, (O35) Author Index i211

Mercer, L. K., i25, (O07), i89, Narayan, N., i195, (E65) Omer, R., i201, (E83) Plenge, R., i150, (259) (099), i135, (221) Naredo, E., i81, (079) Omma, A., i162, (289) Pollard, L., i85, (090) Merkel, P. A., i171, (315), i173, Nash, P., i137, (228) Ong, V. H., i101, (128), i161, (287) Pollock, J., i2, (I09) (317) Nathan, J. A., i191, (E50) Ong, V., i60, (029), i160, (284) Pollock, J., i35, (O25) Merrill, J., i1, (I05) Naylor, S., i199, (E78) Orozco, G., i48, (O52) Poncet, C., i77, (069), i186, (E37) Merris, H., i51, (005) Negi, A., i103, (135), i198, (E76), Orteu, C. H., i160, (284) Ponchel, F., i23, (O04), i81, (078) Meshaka, R., i78, (071) i96, (115) Osborne, D., i89, (100) Ponte, C., i32, (O18), i33, (O19), Meulenbelt, I., i150, (258) Negoescu, A. F., i120, (182), i121, Osborne, N., i201, (E84) i170, (312) Meyfroidt, S., i115, (168) (183), i139, (232) Østergaard, M., i81, (079) Poole, K. ES., i131, (212) Mian, A. N., i24, (O06), i82, (082), Nel, L., i95, (113) Ostor, A. J. K., i91, (103) Poornesh, K., i53, (009) i85, (090), i88, (097) Nelson, I., i60, (030) Ostor, A., i79, (073) Porcheret, M., i67, (046) Middleton, D., i77, (068) Newton, J. L., i132, (215) O¨ sto¨ r, A., i72, (059) Porter, J. C., i41, (O39) Mihai, C., i62, (035) Newton, L. R., i54, (013), i120, Ottewell, L., i181, (E22) Potter, T., i55, (017), i118, (175) Millar, A., i53, (010), i53, (011) (181) Owaki, H., i125, (194) Poulton, C., i169, (308) Miller, A., i67, (047), i67, (048) Ng, N., i93, (109) Oxtoby, J., i68, (049) Poxon, I., i161, (286) Miller, F. W., i47, (O50) Ng, W.-F., i5, (I28), i131, (213), Prabu, A., i30, (O15) Prahalad, S., i148, (252) Miller, J., i204, (E94) i132, (215) Paccou, J., i129, (207), i130, I74 Prakash, A., i147, (250) Milling, S., i14, ( ) Ngcozana, T., i101, (128) (208), i130, (209) Milman, N., i171, (315) Prakash, J. A. J., i122, (187) Nguyen, H., i101, (129) Pachman, L. M., i47, (O50) 146 Prasad, R., i175, (E02) Minaur, N., i107, ( ) Ni Gabhann, J., i30, (O13) Packham, J. C., i48, (O51), i48, Ming Hao, C., i187, (E41) 126 Prathapsingh, M., i55, (016) Ni Mhuiri, A., i100, ( ) (O53), i134, (220), i135, (221), Ming, C. R., i89, (100), i123, (189) Nicholls, E., i40, (O36), i63, (037) Pratt, A. G., i69, (053), i70, (054) i189, (E46) Misra, D. P., i94, (110), i169, (307) Nightingale, A. L., i67, (048) Prease, C., i131, (213) Pagliarini, S., i51, (005) Misra, R., i94, (110), i169, (307) Nightingale, P., i33, (O21), i87, Price, E., i131, (213), i147, (251) Pakozdi, A., i103, (134) Mistry, A., i169, (308) (094) Price-Forbes, A. N., i78, (071) Palmer, E., i77, (068) Mittal, G., i181, (E23), i182, (E26) 178 Pricop, L., i137, (228) Nightingale, R., i119, ( ) Pande, I., i74, (062) Mitton, K., i191, (E50) 282 Prieto-Alhambra, D., i67, (047), Nihtyanova, S. I., i159, ( ), Parajuli, B., i155, (271) Mmesi, J., i193, (E60), i199, (E77) i117, (173), i118, (176) i160, (284), i161, (287) Parida, S. S., i125, (195) Mohamed, A. A. A., i164, (295) Prior, J., i68, (051) Nikiphorou, E., i10, (I46), i24, Parker, B., i30, (O15) Mohammed, A., i168, (305) Prior, Y., i3, (I18), i101, (130), (O05), i79, (073), i82, (081), Parraga Prieto, C., i123, (189) Mokhtar, I., i148, (254) i111, (158), i117, (172), i121, i84, (088), i90, (101), i90, Parry, J., i182, (E26) Molberg, Ø, i47, (O50) (184) (102), i120, (182), i121, (183), Parsons, C., i61, (033), i63, (038), Mo¨ ller, I., i81, (079) Prothero, L., i75, (063), i189, (E45) i139, (232), i199, (E80) i124, (192), i129, (205) Mooney, J., i22, (O02) Prowse, P., i36, (O29) Nisar, M. K., i91, (103) Paskins, Z., i128, (202), i143, Moons, P., i111, (156) Puntmann, V., i166, (300) Nisar, M., i77, (068) 241 Moore, A., i36, (O27), i108, (150) ( ) Purva, M., i147, (250) Nishikawa, M., i125, (194) Patel, H., i60, (029) Moore, O. A., i97, (119), i114, (165) Pye, S. R., i79, (072), i185, (E34) Nixon, N. B., i48, (O51) 304 Moore, T., i34, (O22), i161, (286) Patel, S., i168, ( ) Pyne, D., i103, (134), i196, (E70), Noddings, R., i36, (O28) Patel, V., i137, (227) Moorthy, A., i137, (226) i203, (E92) Norris, J., i69, (053) 132 Moots, R., i17, (I86) Paterson, H., i102, ( ) Pyrkotsch, P., i34, (O22) Norton, S., i24, (O05), i82, (081), Pathan, E. M. I., i136, (224), i198, Mor, A., i124, (193), i196, (E67), i88, (097), i90, (101), i90, (102) (E75) i196, (E68) Noutsou, P., i182, (E27) Patterson, K., i99, (124) Querin, H., i170, (312) Morais, S. A., i164, (296) Ntatsaki, E., i146, (248) E33 Quicke, J. G., i112, (159) Morden, A., i67, (046) Pattinson, U., i184, ( ) Nu¨ ßlein, H., i77, (069), i186, (E37) Pattison, J., i95, (113) Morel, J., i25, (O07), i89, (099) Nune, A., i54, (013), i54, (014) 069 E37 Morgan, A. W., i27, (O11), i47, Pavelka, K., i77, ( ), i186, ( ) Raaschou, P., i89, (099) Nurmohamed, M. T., i77, (069), Payne, B., i50, (001) (O49), i51, (004), i149, (255) Radia, S., i191, (E52) i186, (E37) Peall, A., i33, (O20) Morgan, A., i187, (E41) Radstake, T., i47, (O50) Nye, A., i107, (147), i2, (I08) Pearce, F., i169, (309), i169, (310) Morgan, C., i64, (040) Radunovic, A., i140, (234) Pearson, J., i126, (199) Morris, M., i109, (152), i109, (153) Radziszewska, A., i45, (O45) Peat, G., i63, (037) Morris, M., i35, (O25), i107, (146) O’Beirn, P., i58, (026) Radziszewska, A., i155, (273) Peck, J., i171, (315) Morrison, E., i100, (127) O’Brien, L., i142, (236) Rafiq, A., i91, (103) Peerboom, D., i115, (168) Morsley, K., i67, (047), i178, (E10) O’Brien, T., i78, (070) Raghuvanshi, S., i55, (017) Peichl, P., i77, (069), i186, (E37) Moss, K., i192, (E55) O’Brien, T., i95, (113) Rahman, A., i30, (O15), i96, (114), Penn, H., i41, (O38), i119, (180) Mouyis, M., i104, (138), i129, O’Brien, T. D., i82, (080), i144, (243) i203, (E89) Percy, C., i141, (235) (206), i203, (E88) O’Donoghue, J., i170, (312) Rahman, P., i137, (228) Pericleous, C., i41, (O39), i42, Movahedi, M., i79, (072) O’Hanlon, T. P., i47, (O50) Raj, D., i102, (131) (O41) Mpofu, S., i137, (228) O’Leary, N., i34, (O22) Raja, J., i161, (287) Perks, U., i103, (136), i103, (137) Muir, L., i14, (I76) O’Loughlin, R., i89, (100) Rajagopal, V., i176, (E05), i190, Perry, M., i114, (165) Mukherjee, J., i119, (180) O’Neill, A., i55, (015) (E49), i191, (E51) Petelytska, L., i170, (311) Mukherjee, S., i34, (O24) O’Neill, L., i170, (312) Rajendran, S., i171, (313) Peter, H.-H., i186, (E37), i77, (069) Mukhtyar, C., i186, (E36) O’Neill, T., i125, (196), i126, (197), Ralston, S. H., i100, (127) Peterfy, C., i73, (060) Mulla, E., i137, (227) i30, (O14) Ramanan, A., i157, (277) Peters, T., i128, (204) Mullan, R., i80, (075) O’Reilly, D., i97, (117), i97, (118) Ramos-Merino, L., i164, (294) Petersen, S. E., i130, (208) Muller, S., i168, (306) O’Reilly, D. T., i190, (E49), i191, Rangaraj, M. J., i71, (058) Peterson, A., i35, (O25) Mumtaz, A., i80, (075) (E51) Rankin, E., i45, (O47) Petersson, I. F., i62, (035) Munro, N., i105, (142) O’Reilly, K., i191, (E51) Rapley, T., i45, (O46), i132, (215) Peysakhova, Y., i193, (E60), i199, Murray, A., i34, (O22), i161, (286) O’Reilly, R., i190, (E49) Rashed, A., i155, (272) (E77) Murrell, J., i144, (244) O’Riordan, R., i113, (162), i165, Rashid, A., i46, (O48) I53 I54 Mykytenko, G., i170, (311), i190, (297) Pickles, D., i10, ( ), i10, ( ) Ratcliffe, J., i201, (E85) Pickup, L., i33, (O20), i33, (O21), (E48) O’Shea, F., i132, (214), i135, (222) Ratcliffe, J., i6, (I31) i127, (200) Mysler, E., i71, (058) Ocal, L., i162, (289) Rathod, T., i39, (O35) Ogollah, R., i140, (233) Pincus, T., i84, (088), i120, (182), Rauch, C., i77, (069), i186, (E37) Okada, Y., i150, (259) i139, (232), i199, (E80) Rauz, S., i132, (216) Nadesalingam, K., i54, (012), Oldroyd, A., i142, (237), i189, Pinedo-Villanueva, R., i67, (047) Raval, P., i128, (202) i146, (248), i168, (305) (E44), i197, (E72) Pinnell, J., i55, (017) Ravera, F., i34, (O22) Nagano, T., i148, (253) Oldroyd, A., i123, (190) Piper, J., i32, (O18), i33, (O19) Ravindran, J., i175, (E01) Nair, C., i184, (E31) Oliver, S., i112, (160), i113, (161) Pitzalis, C., i41, (O37), i93, (109), Ravindran, V., i79, (074), i171, Nair, N., i70, (054) Oliver, S., i19, (I105) i131, (213), i138, (229) (313) Nandagudi, A., i194, (E63), i198, Ollier, W. E., i47, (O50) Plant, D., i27, (O11), i47, (O49), Rawat, A., i154, (269) (E74) Omar Herdan, O., i84, (086) i148, (254), i149, (255), i149, Rawlings, C., i198, (E76) Nandi, P., i183, (E30) Omar,E.K.,i177,(E07), i180, (E19) (256), i149, (257), i187, (E41) Rawstron, A. C., i81, (078) i212 Author Index

Ray, D. W., i30, (O14) Salai, M., i196, (E68) Shipley, M., i129, (206) Sturt, J., i75, (063) Raychaudhuri, S., i47, (O49) Salisbury, C., i38, (O32) Shufflebotham, J., i113, (163), Su, B., i114, (164) Rayner, F., i56, (018) Salman, S., i95, (112), i196, (E69) i140, (233) Subesinghe, S., i92, (106) Raza, K., i33, (O21), i39, (O34), Salmon, V. E., i109, (152), i109, Sibille, K., i35, (O26) Sudman, M., i148, (252) i42, (O40), i66, (045), i69, (153) Siddle, H. J., i98, (120) Suffield, L., i45, (O45), i155, (273) (052), i110, (154) Sames, E., i102, (132) Siegel, J., i32, (O17) Sulli, A., i34, (O22) Reddy, V., i196, (E70) Sammon, C. J., i67, (048) Silva, M. A., i122, (186) Sun, E., i103, (135) Reed, A. M., i47, (O50) Sampson, R., i204, (E95) Silverthorne, C., i107, (146) Suppiah, R., i173, (317) Reed, M., i36, (O29) Sandhu, K. S., i23, (O03) Simmonds, B., i38, (O32) Suri, P., i150, (258) Rees, F., i64, (039), i165, (298), Sandhu, P. J. S., i23, (O03) Simons, G., i110, (154) Sutcliffe, N., i131, (213) i166, (299) Sangle, S. R., i95, (113), i166, Simpson, C., i115, (169) Sutton, C., i203, (E89) Regan, M., i131, (213) (300) Sin, W., i138, (229) Sutton, E. J., i30, (O15) Rehman, A., i134, (219) Sanyal, K., i166, (300) Singh Kahlon, A., i158, (279) Swale, V. S., i160, (284) Reilly, E., i94, (111) Sapkota, H. R., i56, (019), i177, Singh, A., i205, (E96) Swales, C., i188, (E43) Reilly, P., i201, (E84) (E08), i177, (E09) Singh, P., i158, (279) Syddall, H., i63, (038) Reimer, U., i69, (052) Saravanan, V., i86, (093), i131, Singh, S., i32, (O18), i33, (O19), Symmons, D. P. M., i5, (I30), i22, Reis, A., i48, (O53) (213) i173, (318) (O01), i26, (O09), i27, (O10), Resteghini, P., i151, (261) Sari-Kouzel, H., i177, (E09) Singh, S., i154, (269), i154, (270), i47, (O49), i59, (028), i64, Reynolds, J. A., i30, (O14) Sathathulla, A., i56, (019) i155, (271) (040), i64, (041), i71, (056), Reynolds, T. D., i175, (E02) Sathi, N., i77, (068) Singleton, C., i100, (125) i87, (094), i134, (220), i135, Rhodes, B., i30, (O15) Sattar, N., i87, (094) Sinha, A., i126, (197) (221), i148, (254), i150, (259), Rhys-Dillon, C., i200, (E81) Savanovic-Abel, O., i97, (119), Sinha, R., i91, (104), i124, (191), i177, (E08), i184, (E33) Richards, H., i137, (228) i114, (165) i167, (303) Sznajd, J., i170, (312), i172, (316), Richardson, A., i152, (264) Sawyer, L., i80, (076) Skelton, A., i70, (054) i173, (317) Richardson, J., i168, (306) Saxena, A. K., i154, (270) Skeoch, S. C., i91, (105) Ripoll, V. M., i42, (O41) Scarsbrook, A., i1, (I03), i168, Slack, R. K., i190, (E49), i191, Tahir, H., i133, (218), i137, (228) Ritchie, J., i121, (185) (305) (E51) Tan, G., i138, (229) Ritchie, S., i105, (142) Schett, G., i133, (217) Smith, A., i157, (276) Tan, G., i93, (109) Rizzoli, R., i17, (I90) Schmidt, W. A., i33, (O19) Smith, D., i35, (O26) Tan, T. S. E., i180, (E17) Roane, G., i71, (058) Schmidt, W., i32, (O18) Smith, J., i126, (198) Tan, V., i67, (046) Roberts, C., i34, (O22) Schoenfelder, S., i148, (253) Smith, N., i45, (O46) Tang, E. Y., i57, (021), i138, (230), Roberts, M., i122, (188) Schomberg, L., i202, (E86) Smith, R., i194, (E62) i193, (E59) Robertson, L., i97, (119), i114, Scire´ , C., i62, (035) Smith, S. L., i149, (255) Tansley, S. L., i44, (O44) (165) Scire` , C. A., i26, (O09) Smith, S., i30, (O13) Tapping, P., i46, (O48) Robinson, D. E., i129, (205) Scola, C., i167, (302) Smith, T., i11, (I57), i127, (200) Tattersall, R., i14, (I72), i18, (I91) Robinson, M., i38, (O32) Scott, D. G., i74, (062) Smith, V., i34, (O22) Taylor, A. M., i200, (E82) Robinson, S. M., i20, (I114) Scott, D. GI., i22, (O02) Snowden, N. H., i9, (I41) Taylor, A., i188, (E42) Robinson, S., i36, (O29), i108, Scott, D. L., i6, (I31), i15, (I81), Sobanski, V., i159, (283) Taylor, C., i34, (O22) (148), i109, (151) i24, (O06), i65, (042), i74, Sofat, N., i8, (I35), i158, (280) Taylor, H., i60, (030) Robinson, S., i66, (044) (062), i82, (081), i85, (090), Somerville, S., i68, (049) Taylor, J., i183, (E30) Robson, J. C., i171, (314), i171, i88, (097) Soni, R., i167, (302) Taylor, P., i42, (O40) (315), i172, (316), i173, (317) Scott, I. C., i49, (O54), i70, (055) Southwood, T. R., i156, (274), Teh, L.-S., i30, (O15), i191, (E50), Robson, J., i169, (308) Scott, I., i85, (090) i156, (275) i203, (E89) Roddy, E., i38, (O31), i39, (O35), Scott, K., i14, (I73) Southwood, T., i153, (266) Tennant, A., i121, (184) i68, (051), i113, (163), i140, Secombes, K., i198, (E75) Southworth, S., i132, (216) Tennekone, D., i193, (E60), i199, (233), i152, (263) Seeliger, B., i170, (312), i172, Sowden, E., i57, (021), i193, (E59) (E77) Rodham, K., i9, (I45), i36, (O28) (316), i173, (317) Sparks, C., i59, (027), i192, (E54) Theander, E., i188, (E42) Rodrigues, A. F., i170, (312) Segal, G., i124, (193), i196, (E67), Spector, T. D., i41, (O37), i150, Thom, J., i139, (231) Rogers, P., i62, (035) i196, (E68) (258) Thomas, A., i92, (107) Rohit, M., i155, (271) Segeda, I., i167, (301) Spencer, J., i163, (293) Thomas, E., i63, (037) Rosa, J., i170, (312) Selvan, S., i102, (133), i178, (E10) Spiers, L. N., i112, (159) Thomas, L. W., i41, (O39) Rosser, E., i5, (I29) Selva-O’Callaghan, A., i47, (O50) Spotswood, H., i32, (O17) Thomas, M. J., i39, (O35) Rothwell, S., i47, (O50) Sen, D., i45, (O45), i155, (273) Spring, S., i79, (073) Thomas, R., i188, (E43) Roussou, E., i140, (234), i199, Seneviratne, A. C., i58, (025), Stack, R. J., i110, (154), i132, Thompson, B., i50, (001), i187, (E79) i141, (235) (216) (E38) Routledge, C., i69, (053), i70, Serafim, A. S., i32, (O18), i33, Stack, R., i39, (O34), i66, (045) Thompson, K., i142, (238) (054) (O19) Stamm, T., i110, (154) Thompson, P., i139, (231) Rowell, L., i71, (058) Sergeant, J. C., i64, (040), i64, Stapleton, P. P., i110, (155) Thompson, S. D., i148, (252) Roy, B., i130, (210) (041), i79, (072) Starr, S., i202, (E86) Thompson, S., i130, (210) Royle, J. G., i183, (E30) Sergeant, J., i71, (056), i76, (066) Steel, L., i153, (265) Thomson, W., i5, (I30), i46, (O48), Rubbert-Roth, A., i71, (058) Seymour, J., i202, (E86) Steer, S., i49, (O54), i65, (042), i47, (O49), i148, (252), i153, Rufus, W., i191, (E51) Shah, K., i133, (217) i70, (055), i88, (097), i89, (267), i154, (268), i156, (274), Ruiz-Sada, P., i164, (294) Shah, P., i138, (230) (100), i115, (169) i157, (276) Ruperto, N., i157, (277) Shaikh, M. M., i20, (I108) Stephanou, A., i42, (O41) Thurairajah, T., i147, (250) Rutherford, A. I., i151, (262), i166, Shaikh, M., i56, (020), i196, (E70) Stephens, L., i163, (292) Thwaites, C., i189, (E46) (300) Sharif, A. A., i103, (134) Stern, E., i159, (282) Tiffin, L., i69, (053) Rutter-Locher, Z., i92, (106) Sharpe, R., i82, (081) Steuer, A., i52, (007), i178, (E10) Timmis, A. L., i193, (E60), i199, Ryan, A. W., i48, (O53) Shazar, N., i124, (193) Stevens, D., i147, (251) (E77) Ryan, J. G., i160, (285) Shea, J., i171, (315) Stevenson, K., i68, (049), i113, Tobias, J., i60, (030) Ryan, S.-J., i21, (I116), i109, Sheard, S., i117, (173) (163), i140, (233) Toes, R. M., i22, (O01) (151), i195, (E66) Sheeran, T., i97, (117), i97, (118) Stober, C. B., i143, (240) Tomasson, G., i171, (315) Rynne, M., i86, (093) Sheikh, F., i78, (070), i82, (080), Stockdale, J., i201, (E85) Toms, E., i110, (155) i96, (115) Stoffer, M., i110, (154) Tooth, S., i40, (O36) Sabanathan, A., i146, (249), i147, Shemesh, S., i196, (E67) Stokes, M., i37, (O30) Tower, C., i163, (291), i163, (292) (250), i201, (E83) Shepstone, L., i22, (O02), i38, Stouten, V., i115, (168) Travers, B., i105, (140) Sacre, S., i11, (I60) (O32) Strangfeld, A., i25, (O07), i89, (099) Tresadern, P., i34, (O22) Saeed, A., i80, (075) Sheth, K., i167, (302) Stratton, J., i104, (139) Trickey, J. C., i57, (022) Sahbudin, I., i33, (O20), i33, (O21) Sheth, V., i167, (302) Stratton, R. J., i162, (288) Trinder, S., i159, (283) Sahin, S., i162, (289) Shevchuk, S., i167, (301) Stratton, R., i56, (020), i205, (E96) Trouw, L. A., i22, (O01) Sahinkaya, Y., i162, (289) Shields, A. M., i41, (O37) Strid, J., i8, (I37) Tubach, F., i25, (O07), i89, (099) Saifuddin, A., i182, (E26) Shipley, J., i131, (211) Sturrock, R. D., i136, (224) Tucker, L., i103, (136), i103, (137) Author Index i213

Tugnet, N., i146, (248) Wadge, S., i34, (O23) Wetherly, L., i75, (064), i83, (084) Wrightson, H., i36, (O29) Tuntirungrojchai, P., i192, (E54) Wakefield, R. J., i34, (O24), i76, Whale, J., i78, (070) Wu, F., i102, (131) Turner, S., i68, (049) (065), i81, (079) White, A., i36, (O28) Wyllie, R., i45, (O46) Tyson, S., i117, (172), i121, (184) Walczak, H., i41, (O37) Whittaker, M., i65, (042), i92, Wyszynski, K., i151, (260) Walker, D., i4, (I21), i36, (O29), (106) i74, (062), i108, (148), i109, Wickramaratne, T. S., i116, (170) Uebe, S., i48, (O53) Xing, F., i162, (288) (151) Wig, S., i58, (024) Uitterlinden, A., i150, (258) Xu, D., i91, (105) Walker-Bone, K., i3, (I16), i12, Wijeweera, S., i97, (119) Uner, A., i117, (174) Xue, L., i114, (164) (I62), i117, (174) Wijeyekoon, J., i98, (22) Urban, M., i109, (152), i109, (153) Walport, M., i5, (I27) Wildt, M., i34, (O22) Walsh, C., i68, (051) Wilkie, R., i14, (I78), i35, (O26) Yaari, L., i196, (E67) Valentino, S., i104, (138) Walsh, D. A., i24, (O05), i88, (098), Wilkinson, J., i161, (286) Yalakki, L. J., i166, (300), i192, Van den Zegel, A., i111, (156) i90, (101), i90, (102) Wilkinson, M., i89, (100) (E55) Van der Elst, K., i115, (168) Walsh, N., i4, (I23), i18, (I96), i100, Wilkinson, T. J., i82, (080) Yanny, S., i128, (203) van der Heijde, De´ sire´ e, i137, (126), i106, (144), i109, (152), Wilkinson, T., i78, (070) Yarwood, A., i47, (O49), i148, (228) i109, (153), i112, (160), i113, Williams, A., i3, (I15) (253), i149, (257), i150, (259) van der Pas, S., i63, (038) (161), i126, (199) Williams, D. J., i101, (129) Yasin, S. A., i44, (O44) van der Windt, D., i63, (037), i140, Walsh, S., i87, (095) Williams, D. L., i143, (239) Yates, M., i38, (O33), i65, (043) (233) Walton, T. J., i153, (265) Williams, E. D. R., i131, (212) Yee, C.-S., i30, (O15), i162, (290), van der Zee-Neuen, A., i62, (035) Ward, K. A., i129, (205) Williams, E., i100, (125) i203, (E89) van Laar, J. 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