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Drug Therapy for Rheumatoid Arthritis in Adults: An Update

Comparative Effectiveness Reviews, No. 55

Investigators: Katrina E Donahue, MD, MPH, Dan E Jonas, MD, MPH, Richard A Hansen, PhD, Robert Roubey, MD, Beth Jonas, MD, MPH, Linda J Lux, MPA, Gerald Gartlehner, MD, MPH, Elizabeth Harden, MPH, Tania Wilkins, MS, Visali Peravali, MS, Shrikant I Bangdiwala, PhD, Andrea Yuen, BS, Patricia Thieda, MA, Laura C Morgan, MA, Karen Crotty, PhD, Rishi Desai, MS, and Megan Van Noord, MSIS.

RTI International–University of North Carolina Evidence-based Practice Center
Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Apr.
Report No.: 12-EHC025-EF
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Structured Abstract


Compare the benefits and harms of corticosteroids, oral and biologic disease-modifying antirheumatic drugs (DMARDs) for adults with rheumatoid arthritis.

Data Sources:

English-language articles from 1980 to February 2011 identified through PubMed, Embase, Cochrane Library, and International Pharmaceutical Abstracts; unpublished literature including dossiers from pharmaceutical companies.


Two people independently selected relevant head-to-head trials of any sample size, prospective cohort studies with at least 100 participants, and relevant good- or fair-quality meta-analyses that compared benefits or harms of 14 drug therapies. Retrospective cohort studies were also included for harms. For biologic DMARDs, placebo-controlled, double-blind RCTs were also included. We required trials and cohort studies to have a study duration of at least 12 weeks. Literature was synthesized qualitatively within and between the two main drug classes (oral and biologic DMARDs). Network meta-analysis also was performed to examine the relative efficacy of biologic DMARDs and comparing withdrawal rates from placebo controlled trials.


Head-to-head trials showed no clinically important differences in efficacy among oral DMARD comparisons (methotrexate, sulfasalazine, leflunomide). The only head-to-head trial comparing biologic DMARDs (abatacept vs. infliximab) found no clinically important differences. Combination therapy of biologic DMARDs plus methotrexate improved clinical response rates and functional capacity more than monotherapy with methotrexate. Network meta-analyses found higher odds of reaching ACR 50 response for etanercept compared with most other biologic DMARDs (abatacept, adalimumab, anakinra, infliximab, rituximab, tocilizumab) for methotrexate-resistant patients with active rheumatoid arthritis. Similar overall tolerability profiles were found among oral and biologic DMARDs, but short-term adverse events were more common with biologic DMARDs. Adjusted indirect comparisons of biologic DMARDs found that certolizumab had the most favorable overall withdrawal profile, followed by etanercept and rituximab. Certolizumab had lower relative withdrawal rates due to lack of efficacy than adalimumab, anakinra, and infliximab. Certolizumab and infliximab had more, while etanercept had fewer withdrawals due to adverse events than most other drugs. Evidence was insufficient to assess comparative risk of serious adverse events among biologic DMARDs. Combinations of biologic DMARDs have higher rates of serious adverse events than biologic DMARD monotherapy. Limited data existed for subgroups.


Limited head-to-head comparative evidence does not support one therapy over another for adults with rheumatoid arthritis. Network meta-analyses from placebo-controlled trials of biologics suggest some differences, including higher odds of reaching ACR 50 response, but strength of evidence was low.


Updated June 2012. Errata: Tables 2, 3, and 4 have been corrected.

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. 290-2007-10056-I, Prepared by: RTI International–University of North Carolina Evidence-based Practice Center, Research Triangle Park, NC

Suggested citation:

Donahue KE, Jonas DE, Hansen RA, Roubey R, Jonas B, Lux LJ, Gartlehner G, Harden E, Wilkins T, Peravali V, Bangdiwala SI, Yuen A, Thieda P, Morgan LC, Crotty K, Desai R, Van Noord M. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55. (Prepared by RTI-UNC Evidence-based Practice Center under Contract No. 290-02-0016-I.) Rockville, MD: Agency for Healthcare Research and Quality. April 2012. www.effectivehealthcare.ahrq.gov/reports/final.cfm.

This report is based on research conducted by the RTI International–University of North Carolina (RTI–UNC) Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2007-10056-I). The findings and conclusions in this document are those of the author(s), who are responsible for its content; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help healthcare 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 may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

None of the investigators has any affiliations for financial involvement that conflicts with the material presented in this report.


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AHRQ (US Agency for Healthcare Research and Quality)

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