DOCSLIB.ORG

Efficacy of Pharmacological Treatment in Rheumatoid Arthritis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Efficacy of Pharmacological Treatment in Rheumatoid Arthritis Ann Rheum Dis: first published as 10.1136/annrheumdis-2019-216656 on 7 February 2020. Downloaded from Rheumatoid arthritis CLINICAL SCIENCE Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis Andreas Kerschbaumer ,1 Alexandre Sepriano ,2,3 Josef S Smolen,1 Désirée van der Heijde ,2 Maxime Dougados,4 Ronald van Vollenhoven,5 Iain B McInnes,6 Johannes W J Bijlsma,7 Gerd R Burmester,8 Maarten de Wit ,9 Louise Falzon,10 Robert Landewé5 Handling editor Dimitrios T ABStract Key messages Boumpas Objectives To inform the 2019 update of the European League against Rheumatism (EULAR) ► Additional material is What is already known about this subject? published online only. To view recommendations for the management of rheumatoid ► Since the 2016 update of the recommendations please visit the journal online arthritis (RA). for the management of rheumatoid arthritis (http:// dx. doi. org/ 10. 1136/ Methods A systematic literature research (SLR) annrheumdis- 2019- 216656). (RA), the body of evidence has grown vividly. to investigate the efficacy of any disease- modifying Therefore, this systematic literature research For numbered affiliations see antirheumatic drug (DMARD) (conventional synthetic (SLR) was performed to inform the 2019 end of article. (cs)DMARD, biological (b) and biosimilar DMARD, European League against Rheumatism (EULAR) targeted synthetic (ts)DMARD) or glucocorticoid (GC) task force with the summarised evidence Correspondence to therapy in patients with RA was done by searching on efficacy of conventional and targeted Dr Andreas Kerschbaumer, MEDLINE, Embase and the Cochrane Library for articles Division of Rheumatology, synthetic disease-modifying antirheumatic Department of Medicine 3, published between 2016 and 8 March 2019. drugs (DMARDs), biological DMARDs and Medical University of Vienna, Results 234 abstracts were selected for detailed glucocorticoids. Vienna, Austria; assessment, with 136 finally included. They comprised andreas. kerschbaumer@ the efficacy of bDMARDs versus placebo or other meduniwien. ac. at What does this study add? bDMARDs, efficacy of Janus kinase (JAK) inhibitors ► Trials comparing biological DMARDs have Received 17 November 2019 (JAKi) across different patient populations and shown similar efficacy, regardless of the Revised 7 January 2020 head- to- head of different bDMARDs versus JAKi or underlying mode of action. Accepted 8 January 2020 other bDMARDs. Switching of bDMARDs to other ► Head- to- head trials between Janus kinase (JAK) bDMARDs or tsDMARDs, strategic trials and tapering inhibitors (JAKi) and tumour necrosis factor http://ard.bmj.com/ studies of bDMARDs, csDMARDs and JAKi were inhibitor inhibitors did not reveal clinically assessed. The drugs evaluated included abatacept, important differences in efficacy. adalimumab, ABT-122, baricitinib, certolizumab ► Drug tapering of DMARDs, including JAKi is pegol, SBI-087, CNTO6785, decernotinib, etanercept, possible, especially in patients achieving stable filgotinib, golimumab, GCs, GS-9876, guselkumab, remission. hydroxychloroquine, infliximab, leflunomide, ► Treating patients to target using MRI- defined on September 25, 2021 by guest. Protected copyright. mavrilimumab, methotrexate, olokizumab, otilimab, remission does not lead to better outcomes ► http:// dx. doi. org/ 10.1136/ peficitinib, rituximab, sarilumab, salazopyrine, when compared with a conventional clinical annrheumdis- 2019- 216653 ► http:// dx. doi. org/ 10.1136/ secukinumab, sirukumab, tacrolimus, tocilizumab, treat- to- target strategy. annrheumdis- 2019- 216655 tofacitinib, tregalizumab, upadacitinib, ustekinumab ► http:// dx. doi. org/ 10.1136/ and vobarilizumab. The efficacy of many bDMARDs How might this impact on clinical practice or annrheumdis- 2019- 216821 and tsDMARDs was shown. Switching to another future developments? tumour necrosis factor inhibitor (TNFi) or non-T NFi ► This SLR, alongside with the safety SLR, bDMARDs after TNFi treatment failure is efficacious. provided the 2019 EULAR RA management © Author(s) (or their Tapering of DMARDs is possible in patients achieving recommendations task force with the emerged employer(s)) 2020. Re- use long-standing stringent clinical remission; in patients evidence since 2016. permitted under CC BY-­NC. No with residual disease activity (including patients commercial re- use. See rights and permissions. Published in LDA) the risk of flares is increased during the by BMJ. tapering. Biosimilars are non-inferior to their reference INTRODUCTION products. To provide the task force on the 2019 update To cite: Kerschbaumer A, of the European League against Rheumatism Sepriano A, Smolen JS, et al. Conclusion This SLR informed the task force Ann Rheum Dis Epub ahead regarding the evidence base of various therapeutic (EULAR) recommendations for the pharmacolog- of print: [please include Day regimen for the development of the update of EULAR’s ical management of rheumatoid arthritis (RA) with Month Year]. doi:10.1136/ RA management recommendation. all available evidence that had emerged since the annrheumdis-2019-216656 last update, systematic literature researches (SLRs) Kerschbaumer A, et al. Ann Rheum Dis 2020;0:1–16. doi:10.1136/annrheumdis-2019-216656 1 Ann Rheum Dis: first published as 10.1136/annrheumdis-2019-216656 on 7 February 2020. Downloaded from Rheumatoid arthritis were performed. In 2016, three SLRs were conducted assessing variables, physical function, patient- reported outcomes and efficacy of biological disease- modifying antirheumatic drugs measures of structural damage. (bDMARDs),1 efficacy of glucocorticoids (GCs), conventional Sixteen research questions were defined according to the synthetic (cs) and targeted synthetic (ts) DMARDs,2 and safety of Patient population, Intervention, Control, Outcome (PICO) pharmacological treatments in RA.3 The 2019 update was based principle with the help of the steering committee. All typical RA on two SLRs, one on safety and the present one on efficacy of study populations were included, methotrexate (MTX)- naïve pharmacological interventions in RA. or generally DMARD- naïve patients, csDMARD insufficient The body of evidence has grown vividly in the last 3 years, responders (IR), bDMARD-IR or tsDMARD-IR . Adequately especially regarding tsDMARDs inhibiting Janus Kinase inhib- defined control groups receiving either placebo or active treat- itor (JAKi), novel bDMARDs targeting new as well as established ment were mandatory for inclusion in this analysis. These pathways and trials comparing bDMARDs to other bDMARDs involved the efficacy of bDMARDs with or without csDMARD or tsDMARDs, providing important information on the compar- combination, head- to- head comparisons of bDMARDs and ative efficacy of these compounds.4 Further, studies on tapering switching between different bDMARDs, tapering and stopping and stopping treatment broaden the information base for rheu- bDMARDs, as well as the efficacy of tsDMARDs and the respec- matologists and patients on the question of possible disease tive head- to- head comparison to bDMARDs. Other research flares after tapering or cessation of drugs, once patients have questions involved biosimilars, switching between bsDMARDs reached the clinical target. Strategic studies on how to optimally and respective boDMARD, the efficacy of csDMARDs and the treat patients to target,5 using clinical and imaging targets have efficacy of GC (in combination with csDMARDs). All interven- also answered important research questions.6 Finally, a large tions of interest are shown in online supplementary table S1.7. number of trials compared the efficacy and safety of biosimilars A detailed description of the PICOs is shown in online supple- (bs) DMARDs with those of their bio-originators (bo), including mentary table S1.8. switching between boDMARD and respective bsDMARDs. Risk of bias (RoB) in individual studies was assessed at study This SLR was conducted to update the evidence on efficacy of level using the Cochrane Collaborations Risk of Bias tool for pharmacological interventions in RA. This involves the evidence randomised controlled trials (RCTs). The assessment was done accrued since the last update of the treatment recommendations independently by two investigators (AK and AS). Differing for RA, published by EULAR in 2016.7 Another SLR focusing assessments were discussed until consensus was reached. on safety of pharmacological treatments in RA is published Due to the heterogeneity of the available studies, no meta- separately.8 analysis was performed, and results will be reported narra- tively. Descriptive forest plots were created using RevMan V.5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane METHODS Collaboration, 2014). The EULAR updated standard operating procedures were followed,9 and an SLR protocol was developed and approved by the steering committee. RESULTS Studies eligible for inclusion in this SLR were randomised, The study selection process involved 15 037 references. After controlled, double-blind trials investigating csDMARDs, deduplication, 7876 remained for title and abstract screening, of bDMARDs (bo and bsDMARDs), tsDMARDs or GCs in adult which 234 were selected for full article review and 136 articles patients with RA classified according to the 2010 American finally included. A detailed flow chart is depicted in figure 1. http://ard.bmj.com/ College of Rheumatology (ACR)/EULAR
Load more

Recommended publications
  • (COVID-19) in the Era of Cardiac Vigilance: a Systematic Review
    Journal of Clinical Medicine Review Repurposing Immunomodulatory Therapies against Coronavirus Disease 2019 (COVID-19) in the Era of Cardiac Vigilance: A Systematic Review Courtney M. Campbell 1,* , Avirup Guha 2 , Tamanna Haque 3, Tomas G. Neilan 4 and Daniel Addison 1,5 1 Cardio-Oncology Program, Division of Cardiology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, OH 43210, USA; [email protected] 2 Harrington Heart and Vascular Institute, Case Western Reserve University, Cleveland, OH 44106, USA; [email protected] 3 Division of Hematology/Oncology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, OH 43210, USA; [email protected] 4 Cardio-Oncology Program, Division of Cardiology, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA 02144, USA; [email protected] 5 Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210, USA * Correspondence: [email protected] Received: 23 July 2020; Accepted: 8 September 2020; Published: 11 September 2020 Abstract: The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in efforts to identify therapies to ameliorate adverse clinical outcomes. The recognition of the key role for increased inflammation in COVID-19 has led to a proliferation of clinical trials targeting inflammation. The purpose of this review is to characterize the current state of immunotherapy trials in COVID-19, and focuses on associated cardiotoxicities, given the importance of pharmacovigilance. The search terms related to COVID-19 were queried in ClinicalTrials.gov. A total of 1621 trials were identified and screened for interventional trials directed at inflammation.
    [Show full text]
  • Q3 2020 Results
    Q3 2020 Results 28 October 2020 Cautionary statement regarding forward-looking statements This presentation may contain forward-looking statements. Forward-looking statements give the Group’s current expectations or forecasts of future events. An investor can identify these statements by the fact that they do not relate strictly to historical or current facts. They use words such as ‘anticipate’, ‘estimate’, ‘expect’, ‘intend’, ‘will’, ‘project’, ‘plan’, ‘believe’, ‘target’ and other words and terms of similar meaning in connection with any discussion of future operating or financial performance. In particular, these include statements relating to future actions, prospective products or product approvals, future performance or results of current and anticipated products, sales efforts, expenses, the outcome of contingencies such as legal proceedings, dividend payments and financial results. Other than in accordance with its legal or regulatory obligations (including under the Market Abuse Regulations, UK Listing Rules and the Disclosure Guidance and Transparency Rules of the Financial Conduct Authority), the Group undertakes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Investors should, however, consult any additional disclosures that the Group may make in any documents which it publishes and/or files with the US Securities and Exchange Commission (SEC). All investors, wherever located, should take note of these disclosures. Accordingly, no assurance can be given that any particular expectation will be met and investors are cautioned not to place undue reliance on the forward-looking statements. Forward-looking statements are subject to assumptions, inherent risks and uncertainties, many of which relate to factors that are beyond the Group’s control or precise estimate.
    [Show full text]
  • Q3 2019 Results
    Q3 2019 Results 30 October 2019 Cautionary statement regarding forward-looking statements This presentation may contain forward-looking statements. Forward-looking statements give the Group’s current expectations or forecasts of future events. An investor can identify these statements by the fact that they do not relate strictly to historical or current facts. They use words such as ‘anticipate’, ‘estimate’, ‘expect’, ‘intend’, ‘will’, ‘project’, ‘plan’, ‘believe’, ‘target’ and other words and terms of similar meaning in connection with any discussion of future operating or financial performance. In particular, these include statements relating to future actions, prospective products or product approvals, future performance or results of current and anticipated products, sales efforts, expenses, the outcome of contingencies such as legal proceedings, dividend payments and financial results. Other than in accordance with its legal or regulatory obligations (including under the Market Abuse Regulations, UK Listing Rules and the Disclosure Guidance and Transparency Rules of the Financial Conduct Authority), the Group undertakes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Investors should, however, consult any additional disclosures that the Group may make in any documents which it publishes and/or files with the US Securities and Exchange Commission (SEC). All investors, wherever located, should take note of these disclosures. Accordingly, no assurance can be given that any particular expectation will be met and investors are cautioned not to place undue reliance on the forward-looking statements. Forward-looking statements are subject to assumptions, inherent risks and uncertainties, many of which relate to factors that are beyond the Group’s control or precise estimate.
    [Show full text]
  • Inflammatory Response in Children & Adults
    INFLAMMATORY RESPONSE IN CHILDREN & ADULTS JUNE 3, 2020 WEBINAR SERIES PARTNERS American Academy of Clinical Toxicology (AACT) American Academy of Emergency Medicine (AAEM) American Academy of Emergency Nurse Practitioners (AAENP) American Association of Poison Control Centers (AAPCC) American College of Medical Toxicology (ACMT) Asia Pacific Association of Medical Toxicologists (APAMT) European Association of Poison Centers and Clinical Toxicologists (EAPCCT) Middle East & North Africa Clinical Toxicology Association (MENATOX) ON-DEMAND RESOURCES All webinars are recorded and www.acmt.net/covid19web Questions? posted to the ACMT website Write to: [email protected] Q&A will be at end of the Webinar Please type your questions into the Q&A or Chat function during the webinar and we will get to as many as we can We monitor all platforms, including YouTube and Facebook, for questions MODERATORS Paul M. Wax, MD FACMT ¡ Executive Director, American College of Medical Toxicology (ACMT) Ziad Kazzi, MD, FACMT ¡ Board Member, American College of Medical Toxicology (ACMT) ¡ President, Middle East & North Africa Clinical Toxicology Association (MENATOX) MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN (MIS-C) MEDICAL AND PUBLIC HEALTH CONSIDERATIONS OF COVID-19 James Schneider, MD, FAAP, FCCP Chief, Pediatric Critical Care Medicine, Associate Professor of Pediatrics, Cohen Children’s Medical Center, New Hyde Park, NY [email protected] CONFLICT OF THIS SPEAKER DOES NOT HAVE ANY CONFLICTS OF INTEREST INTEREST TO DISCLOSE Recognition of New disease?
    [Show full text]
  • Immunomodulators Under Evaluation for the Treatment of COVID-19
    Immunomodulators Under Evaluation for the Treatment of COVID-19 Last Updated: August 4, 2021 Summary Recommendations See Therapeutic Management of Hospitalized Adults with COVID-19 for the COVID-19 Treatment Guidelines Panel’s (the Panel) recommendations on the use of the following immunomodulators for patients according to their disease severity: • Baricitinib with dexamethasone • Dexamethasone • Tocilizumab with dexamethasone Additional Recommendations There is insufficient evidence for the Panel to recommend either for or against the use of the following immunomodulators for the treatment of COVID-19: • Colchicine for nonhospitalized patients • Fluvoxamine • Granulocyte-macrophage colony-stimulating factor inhibitors for hospitalized patients • Inhaled budesonide • Interleukin (IL)-1 inhibitors (e.g., anakinra) • Interferon beta for the treatment of early (i.e., <7 days from symptom onset) mild to moderate COVID-19 • Sarilumab for patients who are within 24 hours of admission to the intensive care unit (ICU) and who require invasive mechanical ventilation, noninvasive ventilation, or high-flow oxygen (>0.4 FiO2/30 L/min of oxygen flow) The Panel recommends against the use of the following immunomodulators for the treatment of COVID-19, except in a clinical trial: • Baricitinib with tocilizumab (AIII) • Interferons (alfa or beta) for the treatment of severely or critically ill patients with COVID-19 (AIII) • Kinase inhibitors: • Bruton’s tyrosine kinase inhibitors (e.g., acalabrutinib, ibrutinib, zanubrutinib) (AIII) • Janus kinase inhibitors other than baricitinib (e.g., ruxolitinib, tofacitinib) (AIII) • Non-SARS-CoV-2-specific intravenous immunoglobulin (IVIG) (AIII). This recommendation should not preclude the use of IVIG when it is otherwise indicated for the treatment of complications that arise during the course of COVID-19.
    [Show full text]
  • Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis
    REVIEW published: 09 July 2021 doi: 10.3389/fimmu.2021.686155 Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis † † Jie Huang 1 , Xuekun Fu 1 , Xinxin Chen 1, Zheng Li 1, Yuhong Huang 1 and Chao Liang 1,2* 1 Department of Biology, Southern University of Science and Technology, Shenzhen, China, 2 Institute of Integrated Bioinfomedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of the population worldwide. With the sustained development of disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing and relieving disease activity in RA patients. Unfortunately, some patients still show limited response to DMARDs, which puts forward new requirements for special targets and novel therapies. Understanding the pathogenetic roles of the various molecules in RA could facilitate discovery of potential therapeutic targets and approaches. In this review, both Edited by: existing and emerging targets, including the proteins, small molecular metabolites, and Trine N. Jorgensen, epigenetic regulators related to RA, are discussed, with a focus on the mechanisms that Case Western Reserve University, result in inflammation and the development of new drugs for blocking the various United States modulators in RA. Reviewed by: Åsa Andersson, Keywords: rheumatoid arthritis, targets, proteins, small molecular metabolites, epigenetic regulators Halmstad University, Sweden Abdurrahman Tufan, Gazi University, Turkey *Correspondence: INTRODUCTION Chao Liang [email protected] Rheumatoid arthritis (RA) is classified as a systemic poly-articular chronic autoimmune joint † disease that primarily affects hands and feet.
    [Show full text]
  • Bispecific T-Cell Redirection Versus Chimeric Antigen Receptor (CAR)-T Cells As Approaches to Kill Cancer Cells
    Bispecific T-Cell Redirection versus Chimeric Antigen Receptor (CAR)-T Cells as Approaches to Kill Cancer Cells William R. Strohl 1,* and Michael Naso 2 1 BiStro Biotech Consulting, LLC, 1086 Tullo Farm Rd., Bridgewater, NJ 08807, USA 2 Century Therapeutics, 3675 Market St., Philadelphia, PA 19104, USA * Correspondence: [email protected]; Tel.: +1-908-745-8576 Received: 27 May 2019; Accepted: 24 June 2019; Published: 3 July 2019 Abstract: The concepts for T-cell redirecting bispecific antibodies (TRBAs) and chimeric antigen receptor (CAR)-T cells are both at least 30 years old but both platforms are just now coming into age. Two TRBAs and two CAR-T cell products have been approved by major regulatory agencies within the last ten years for the treatment of hematological cancers and an additional 53 TRBAs and 246 CAR cell constructs are in clinical trials today. Two major groups of TRBAs include small, short- half-life bispecific antibodies that include bispecific T-cell engagers (BiTE®s) which require continuous dosing and larger, mostly IgG-like bispecific antibodies with extended pharmacokinetics that can be dosed infrequently. Most CAR-T cells today are autologous, although significant strides are being made to develop off-the-shelf, allogeneic CAR-based products. CAR-Ts form a cytolytic synapse with target cells that is very different from the classical immune synapse both physically and mechanistically, whereas the TRBA-induced synapse is similar to the classic immune synapse. Both TRBAs and CAR-T cells are highly efficacious in clinical trials but both also present safety concerns, particularly with cytokine release syndrome and neurotoxicity.
    [Show full text]
  • Cellular Immunology the Role of B Cells in Multiple Sclerosis
    Cellular Immunology 339 (2019) 10–23 Contents lists available at ScienceDirect Cellular Immunology journal homepage: www.elsevier.com/locate/ycimm Research paper ☆ The role of B cells in multiple sclerosis: Current and future therapies T ⁎ Austin Negrona, Rachel R. Robinsona, Olaf Stüveb,c, Thomas G. Forsthubera, a Department of Biology, University of Texas at San Antonio, TX 78249, USA b Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA c Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA ABSTRACT While it was long held that T cells were the primary mediators of multiple sclerosis (MS) pathogenesis, the beneficial effects observed in response to treatment with Rituximab (RTX), a monoclonal antibody (mAb) targeting CD20, shed light on a key contributor to MS that had been previously underappreciated: B cells. This has been reaffirmed by results from clinical trials testing the efficacy of subsequently developed B cell-depleting mAbs targeting CD20 as well as studies revisiting the effects of previous disease-modifying therapies (DMTs) on B cell subsets thought to modulate disease severity. In this review, we summarize current knowledge regarding the complex roles of B cells in MS pathogenesis and current and potential future B cell-directed therapies. 1. Introduction oligoclonal bands [12–14]. However, unlike what is observed in NMO and MG, there is significant heterogeneity in the antigen specificity of The contribution of B cells to autoimmune disease pathogenesis has these oligoclonal antibodies, which may target pathogens as well as historically been viewed primarily via the production of pathogenic autoantigens [8].
    [Show full text]
  • Overview of Planned Or Ongoing Studies of Drugs for the Treatment of COVID-19
    Version of 16.06.2020 Overview of planned or ongoing studies of drugs for the treatment of COVID-19 Table of contents Antiviral drugs ............................................................................................................................................................. 4 Remdesivir ......................................................................................................................................................... 4 Lopinavir + Ritonavir (Kaletra) ........................................................................................................................... 7 Favipiravir (Avigan) .......................................................................................................................................... 14 Darunavir + cobicistat or ritonavir ................................................................................................................... 18 Umifenovir (Arbidol) ........................................................................................................................................ 19 Other antiviral drugs ........................................................................................................................................ 20 Antineoplastic and immunomodulating agents ....................................................................................................... 24 Convalescent Plasma ...........................................................................................................................................
    [Show full text]
  • MRI of the Joint and Evaluation of the Granulocyte–Macrophage Colony
    This is a repository copy of MRI of the joint and evaluation of the granulocyte–macrophage colony-stimulating factor–CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic study. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/162810/ Version: Supplemental Material Article: Genovese, MC, Berkowitz, M, Conaghan, PG orcid.org/0000-0002-3478-5665 et al. (14 more authors) (2020) MRI of the joint and evaluation of the granulocyte–macrophage colony-stimulating factor–CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic study. Lancet Rheumatology, 2 (11). e666- e676. ISSN 2665-9913 https://doi.org/10.1016/S2665-9913(20)30224-1 © 2020, Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/. Reuse This article is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) licence. This licence only allows you to download this work and share it with others as long as you credit the authors, but you can’t change the article in any way or use it commercially. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ SUPPLEMENTARY INFORMATION Supplementary methods Protocol amendments 1.
    [Show full text]
  • GSK Announces Results Evaluating Its Investigational Monoclonal Antibody, Otilimab, for the Treatment of Hospitalised Adult Patients with COVID-19
    RNS Number : 3602Q GlaxoSmithKline PLC 25 February 2021 Issued: 25 February 2021, London UK GSK announces results evaluating its investigational monoclonal antibody, otilimab, for the treatment of hospitalised adult patients with COVID-19 GlaxoSmithKline plc (LSE/NYSE: GSK)todayannouncedresults fromthephase 2 proof of concept OSCAR (Otilimabin Severe COVID-19 Related Disease) study withotilimab, an investigational anti-granulocyte macrophage colony- stimulating factor (anti-GM-CSF) monoclonal antibody. The primary endpoint of the OSCAR study was the proportion of COVID-19 patients who were alive and free of respiratory failure 28 days after treatment with a single dose of otilimab in addition to standard of care (including anti- viral treatments and corticosteroids), compared to patients being treated with standard of care alone. Data from patients of all ages showed a treatment difference of 5.3% (95% CI= -0.8%, 11.4%) but this did not reach statistical significance. However, a pre-planned efficacy analysis by age in patients 70 years and older (N=180, 806 in total study) showed that 65.1% of patients were alive and free of respiratory failure 28 days after treatment with otilimab plus standard of care, compared to 45.9% of patients who received the standard of care alone (delta of 19.1%, 95% CI=5.2%, 33.1%) (nominal p-value=0.009). In addition, in a mortality analysis up to day 60, a treatment difference of 14.4% favouring otilimab was seen with rates of 40.4% on standard of care vs. 26% on otilimab plus standard of care (95% CI= 0.9%, 27.9%) (nominal p-value=0.040) in patients 70 years and older.
    [Show full text]
  • Beyond Counting Sheep: New Strategies for Sleep Maintenance Insomnia
    Beyond Counting Sheep: New Strategies for Sleep Maintenance Insomnia Beyond Counting Sheep: New Strategies for Sleep Maintenance Insomnia 1 Learning Objectives • Screen patients for insomnia according to current diagnostic criteria • Identify the cause of insomnia, including psychosocial and lifestyle issues and comorbidities, to determine treatment and reduce risk factors • Individualize treatment with approved insomnia medications, including dual orexin receptor antagonists 2 2 Insomnia: Definition and Types Desired • Patient report of difficulty: wake time Sleep-maintenance ‒ Initiating sleep insomnia ‒ Maintaining sleep • Adequate opportunity and circumstances for sleep Sleep-onset • Daytime impairment insomnia Bedtime Sateia MJ. Chest. 2014;146:1387-1394; Sateia MJ, et al. J Clin Sleep Med. 2017;13:307-349. 3 3 2020 PCE Symposia Series 3 1 Beyond Counting Sheep: New Strategies for Sleep Maintenance Insomnia Epidemiology of Insomnia Prevalence of Insomnia Symptoms* in the US Proportion of Patients With Insomnia† Who Discuss Symptoms with HCP 2% 5% Never Never discuss 19% Rarely 33% Mention during discussion 26% of a different problem A few nights per month Specifically seek evaluation 69% A few nights per week 25% for insomnia Every night or almost 21% every night *Insomnia symptoms defined as trouble falling asleep, waking frequently at night, †Insomnia defined as having any history of difficulty sleeping waking too early and unable to fall back asleep, or waking feeling unrefreshed Ancoli-Israel S, et al. Sleep. 1999;22(suppl 2):S347-S353; Bailes S, et al. Fam Pract. 2009;26:294-300; National Sleep Foundation. www.sleepfoundation.org/professionals/sleep-america-polls/2005-adult-sleep-habits-and-styles. Accessed October 19, 2020.
    [Show full text]