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Management of Early Rheumatoid Arthritis

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Management of Early Rheumatoid Arthritis CME Rheumatology Management of Medical management appears to have Rheumatologists now use DMARDs as most to offer in the early stages of the early as possible in the natural history of disease, with the aim of preventing joint the disease. Recent guidelines for the early rheumatoid damage and loss of function. Simple management of RA published by the analgesics and non-steroidal anti-inflam- American College of Rheumatology arthritis matory drugs (NSAIDs) can be used for Subcommittee on Rheumatoid Arthritis pain control but they do not control the Guidelines (2002 update)4 state that: inflammation and joint damage. Shirish Dubey MBBS MRCP(I), Specialist the majority of patients with newly diag- Other drugs, used for control of sys- Registrar, Rheumatology nosed RA should be started on a temic inflammation, are known as dis- disease-modifying antirheumatic drug Karl Gaffney FRCP FRCP(I), Consultant ease-modifying antirheumatic drugs Rheumatologist within three months of the diagnosis. (DMARDs); they include methotrexate, Norfolk and Norwich NHS Trust sulphasalazine, leflunomide, ciclosporin, gold and antimalarials (eg hydroxy- Early inflammatory arthritis Clin Med 2005;5:211–4 chloroquine) and were previously con- sidered as second-line agents. Recently, a A number of factors lead to delay in diag- new class of DMARDs (‘biologics’) has Background nosis and treatment, including: emerged. This group of drugs includes • delay on the part of the patient in Rheumatoid arthritis (RA) is a systemic the anti-tumour necrosis factor agents seeking medical care (discussed in the accompanying article autoimmune disorder of unknown delay in primary care aetiology characterised by symmetrical Beyond methotrexate: biologic therapy • waiting time to be assessed in polyarthritis of the small and large joints. in rheumatoid arthritis). • secondary care The cardinal history features of active RA Traditionally, the treatment of RA are: revolved around control of symptoms, • time to initiation of a DMARD in secondary care. pain with painkillers and NSAIDs, the more • ‘toxic’ agents being used once these drugs Research shows that any delay in initi- early morning stiffness (lasting more • had failed to control the symptoms of ating DMARDs can lead to substantial than 30 min) arthritis (hence, the concept of differences in long-term outcome.5,6 As a • joint swelling second-line agents). Unfortunately, result, the concept of early inflammatory • limitation of function. studies have shown that NSAIDs and arthritis has emerged. The first early Additional features include malaise analgesics have no disease-modifying arthritis cohort was established in 1957 in and fatigue. effects and that irreversible erosive Bath but the concept of early arthritis Chronic synovitis, with its attendant changes occur early in the course of the clinics emerged only in the late 1980s.7 In synovial proliferation, can lead to ero- disease. Within three months of disease recent years, a number of studies have sions, destruction of the cartilage and onset, 10–26% of patients will have joint focused on early inflammatory arthritis, instability of the joint, leading in turn to erosions evident on X-ray2 – the figure addressing whether early treatment with considerable disability. Furthermore, may be greater with imaging modalities DMARDs improves outcome. In several about a third of patients with RA will like magnetic resonance imaging and placebo-controlled studies in early stop working due to disease progression ultrasound. Within five years, about 95% arthritis (duration <2 years) using agents within five years.1 In the US, the esti- of patients are likely to have erosive dis- like methotrexate, sulphasalazine, gold mated yearly cost of RA is $9 billion, with ease.3 With increasing knowledge about and hydroxychloroquine, patients treated $4 billion in lost earnings alone. long-term prognosis and the risks of with DMARDs showed significant reduc- Consequently, RA has a profound impact delaying potentially disease-modifying tion in signs and symptoms and improved on patients, families and society in therapy, there has been a marked change patient function.8 Similar results are seen general. in the management of early RA. with oral prednisolone, which seems to have both symptom controlling and dis- 9 Key Points ease-modifying effects. Analysis of delayed treatment trials (extensions of placebo-controlled treatment investiga- For patients in whom inflammatory arthritis is suspected, the presence of polyarticular symptoms, particularly with hand or foot involvement and morning tions in which the placebo group is stiffness more than 30 minutes warrants specialist opinion switched to active treatment at the end point of the initial study) shows that the Disease-modifying antirheumatic drugs (DMARDs) are started early in the treatment early treatment group had significantly of inflammatory arthritis, sometimes even before the confirmation of diagnosis better efficacy parameters, including KEY WORDS: disease-modifying antirheumatic drugs (DMARDs), early arthritis, improved patient function (reduced rheumatoid arthritis, treatment Health Assessment Questionnaire Clinical Medicine Vol 5 No 3 May/June 2005 211 CME Rheumatology scores), decreased swollen joint counts, taken further. Patients with early arthritis • joint swelling of three or more joints and reduced or slowed radiographic were divided into two groups and • metacarpophalangeal or progression.10–12 outcomes assessed separately: metatarsophalangeal involvement In addition to monotherapy with • very early RA (VERA): duration less • morning stiffness of more than 30 DMARDs, a number of DMARD combi- than three months minutes. nations have been studied and may have • late early RA (LERA): duration less superior efficacy compared with than one year. monotherapy in early disease, but those Baseline investigations (Table 2) Although the inflammatory markers that do not include methotrexate fail to and swollen joint counts were no dif- Baseline laboratory investigations should show the same levels of efficacy. The ferent, patients in the VERA group had include: combinations include: better control of symptoms and signs full blood count methotrexate/sulphasalazine/ • • and better retardation of radiological erythrocyte sedimentation rate steroids13 • progression.16 These studies highlight (ESR) methotrexate/hydroxychloroquine • the importance of an early aggressive C-reactive protein methotrexate/ciclosporin approach in improving both the disease • • rheumatoid factor methotrexate/leflunomide. course and outcome. • • renal function tests Further support for early intervention • liver function tests (including comes from a review of primary trial Practical management of early • hepatic enzymes, alkaline data from 14 randomised controlled inflammatory arthritis phosphatase and albumin) trials of DMARD therapy in early RA. This indicated that disease duration was Referral • urinalysis. In certain instances, a synovial fluid a significant determinant of response to The therapeutic studies in early arthritis analysis may be deemed necessary to treatment, patients with shorter disease studies suggest a ‘window of opportu- 8,14 exclude other differential diagnoses like duration responding more favourably. nity’ in RA when DMARDs are more septic arthritis or crystal arthritis. The likely to be successful. Unfortunately, it assessment of renal and hepatic function can be hard to diagnose RA early in the Safety of early intervention tests is necessary as a number of treat- course of the illness (Table 1) and may ments (including NSAIDs) can cause An inception cohort (wherein a selection take some months before the classifica- renal and/or hepatic damage and may be of new patients are followed from tion criteria are fulfilled. Delays in con- contraindicated in the presence of presentation onwards) of 622 patients firming the diagnosis might mean that impairment of these organs. with newly diagnosed RA were followed any ‘therapeutic window of opportunity’ for up to 10 years to evaluate patient is missed. Baseline clinical assessment mortality, functional ability and prog- should include symptoms of active dis- Prognosis nostic factors for mortality.15 This ease (history of joint pain and swelling, In addition to these baseline laboratory cohort, treated early and aggressively duration of morning stiffness, diurnal investigations, the patient should be with DMARDs, showed no excess mor- variation of symptoms), functional assessed for comorbid conditions, and a tality within the first 10 years, and func- status and examination evidence of validated tool used to assess pain, disease tional ability remained constant after an synovitis. initial improvement from baseline. The clinical criteria that should In a recent prospective study, the con- prompt referral to a rheumatologist and cept of early inflammatory arthritis was to the early arthritis clinic are:8 Table 2. Baseline assessment of patients with inflammatory arthritis. G Symptoms of active disease Table 1. American College of Rheumatology 1987 revised criteria for classification of G Functional status (eg HAQ) rheumatoid arthritis.17 G Clinical evidence of synovitis G Extra-articular disease G Morning stiffness lasting more than 1 hour G Radiographic damage G Arthritis of 3 or more joint areas Need to be present for at least 6 weeks G Laboratory investigations including: G } Arthritis of hand joints – FBC, ESR, U&Es, LFTs, RF Symmetric arthritis – Urinalysis Rheumatoid nodules Rheumatoid
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