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Structured Abstract
Objectives:
Compare the benefits and harms of drug therapies for adults with early rheumatoid arthritis (RA) within 1 year of diagnosis, updating the findings on early RA from the 2012 review.
Data sources:
English-language articles identified through MEDLINE®, Cochrane Library, Embase®, International Pharmaceutical Abstracts, gray literature, the previous 2012 review, expert recommendations, reference lists of published literature, and supplemental evidence data requests from January 2011 to October 5, 2017.
Review methods:
Literature was synthesized qualitatively in narrative form and summary tables within and between corticosteroids and classes of disease-modifying antirheumatic drugs (DMARDs). Additionally, combination treatment strategies were examined. We conducted network meta-analysis for five outcomes: American College of Rheumatology 50-percent improvement (ACR50), remission based on Disease Activity Score (DAS), radiographic joint damage, all discontinuations, and discontinuations due to adverse events. Eligibility for network meta-analyses required the following: (1) patients with early RA had not attempted prior treatment with methotrexate (MTX), (2) doses of treatments were within ranges approved by the Food and Drug Administration (FDA), (3) length of followup was similar, and (4) studies were double-blinded randomized controlled trials of low or medium risk of bias.
Results:
We analyzed 49 studies: 41 RCTs and 8 observational studies reported in 124 published articles. All included studies enrolled patients with moderate to high disease activity at baseline as measured with mean or median DAS 28 scores. A combination of corticosteroids plus MTX achieved higher remission rates than with MTX monotherapy (low strength of evidence [SOE]). Combination therapy with TNF (tumor necrosis factor) or non-TNF biologics plus MTX improved disease control, remission, and functional capacity compared with monotherapy with either MTX or a biologic (low to moderate SOE). Network meta-analyses found higher ACR50 response for combination therapy of biologics plus MTX than for MTX monotherapy (range of relative risk, 1.20 [95% confidence interval (CI), 1.04 to 1.38] to 1.57 [95% CI, 1.30 to 1.88]). In available data, consisting mostly of clinical trials, no significant differences emerged between any DMARDs for rates of discontinuation attributable to adverse events or serious adverse events (low SOE for adalimumab, certolizumab pegol, etanercept, infliximab, or abatacept with MTX, and moderate SOE for rituximab or tocilizumab with MTX). Data about subgroups (based on disease activity, prior therapy, demographics, and the presence of other serious conditions) were insufficient. No difference in findings were noted in MTX naïve and resistant populations. We found no studies of biosimilars for patients with early RA.
Conclusions:
Qualitative synthesis and network meta-analyses suggest that the combination of MTX with TNF or non-TNF biologics improves disease activity and remission when compared with biologic monotherapy or a conventional synthetic DMARD (csDMARD) monotherapy in patients with moderate to high disease activity at baseline as measured with mean or median DAS 28 scores. Overall rates of adverse events and discontinuation were similar among patients given csDMARDs, TNF biologics, and non-TNF biologics. We did not find eligible studies of biosimilars.
Contents
- Purpose and Key Messages
- Preface
- Acknowledgments
- Evidence Summary
- Introduction
- Methods
- Criteria for Inclusion/Exclusion of Studies in the Review
- Searching for the Evidence: Literature Search Strategies for Identification of Relevant Studies To Answer the Key Questions
- Literature Review, Data Abstraction, and Data Management
- Assessment of Methodological Risk of Bias of Individual Studies
- Data Synthesis
- Grading the Strength of Evidence for Major Comparisons and Outcomes
- Assessing Applicability
- Peer Review and Public Commentary
- Results
- Organization of the Results
- Search Results
- KQ 1. Comparative Benefits of Drug Therapies for Patients With Early RA in Relation to Disease Activity, Progression of Radiographic Joint Damage, or Remission
- KQ 2. Comparative Benefits of Drug Therapies for Patients With Early RA in Relation to Patient-Reported Symptoms, Functional Capacity, or Quality of Life
- KQ 3. Comparative Harms of Drug Therapies for Patients With Early RA in Relation to Harms, Tolerability, Patient Adherence, or Adverse Effects
- KQ 4. Comparative Benefits and Harms in Subgroups of Patients
- Discussion
- Abbreviations and Acronyms
- Appendix A. Search Strings
- Appendix B. Excluded Articles
- Appendix C. Detailed Evidence Table
- Appendix D. Risk of Bias Ratings and Rationales for Included Studies
- Appendix E. Strength of Evidence for Key Questions 1–4 Outcomes
- Appendix F. Eligible Clinical and Self-Reported Scales and Instruments Commonly Used in Eligible Studies of Drug Therapy for Rheumatoid Arthritis
- Appendix G. Tests of Consistency for Main Network Meta-Analyses
- Appendix H. Supplementary Primary Network Meta-Analyses
- Appendix I. Sensitivity Analyses for Network Meta-Analyses
- Appendix J. Expert Guidance and Review
- Appendix K. PCORI Methodology Standards Checklist: SER Update
- Report References
Suggested citation:
Donahue KE, Gartlehner G, Schulman ER, Jonas B, Coker-Schwimmer E, Patel SV, Weber RP, Lohr KN, Bann C, Viswanathan M. Drug Therapy for Early Rheumatoid Arthritis: A Systematic Review Update. Comparative Effectiveness Review No. 211. (Prepared by the RTI International–University of North Carolina at Chapel Hill Evidence-based Practice Center under Contract No. 290-2015-00011-I for AHRQ and PCORI.) AHRQ Publication No. 18-EHC015-EF. PCORI Publication No. 2018-SR-02. Rockville, MD: Agency for Healthcare Research and Quality; July 2018. Posted final reports are located on the Effective Healthcare Program search page. https://doi.org/10.23970/AHRQEPCCER211.
This report is based on research conducted by the RTI International–University of North Carolina at Chapel Hill Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00011-I). The Patient-Centered Outcomes Research Institute (PCORI) funded the report (PCORI Publication No. 2018-SR-02). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ or PCORI. Therefore, no statement in this report should be construed as an official position of PCORI, AHRQ, or of the U.S. Department of Health and Human Services.
None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.
The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.
This report is made available to the public under the terms of a licensing agreement between the author and AHRQ. This report may be used and reprinted without permission except those copyrighted materials that are clearly noted in the report. Further reproduction of those copyrighted materials is prohibited without the express permission of copyright holders.
PCORI, AHRQ, or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.
This report may periodically be assessed for the currency of conclusions. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program Web site at: www.effectivehealthcare.ahrq.gov. Search on the title of the report.
Persons using assistive technology may not be able to fully access information in this report. For assistance contact vog.shh.qrha@cpe.
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