Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis

15 January 2008 | Volume 148 Issue 2 | Pages 124-134

Background: The comparative effectiveness of rheumatoid arthritis therapies is uncertain.

Purpose: To compare the benefits and harms of disease-modifying antirheumatic drugs (DMARDs) for adults with rheumatoid arthritis.

Data Sources: Records limited to the English language and studies of adults were identified by using MEDLINE, EMBASE, The Cochrane Library, and International Pharmaceutical Abstracts from 1980 to September 2007.

Study Selection: Two persons independently selected relevant head-to-head trials and prospective cohort studies with at least 100 participants and 12-week follow-up and relevant good- or fair-quality meta-analyses that compared benefits or harms of 11 drug therapies. For harms, they included retrospective cohort studies.

Data Extraction: Information on study design, interventions, outcomes, and quality were extracted according to a standard protocol.

Data Synthesis: Head-to-head trials (n = 23), mostly examining synthetic DMARDs, showed no clinically important differences in efficacy among synthetic DMARDs (limited to methotrexate, leflunomide, and sulfasalazine) or among anti–tumor necrosis factor drugs (adalimumab, etanercept, and infliximab). Monotherapy with anti–tumor necrosis factor drugs resulted in better radiographic outcomes than did methotrexate but no important differences in clinical outcomes (for example, 20%, 50%, or 70% improvement according to American College of Rheumatology response criteria). Various combinations of biological DMARDs plus methotrexate improved clinical response rates and functional outcomes more than monotherapy with either methotrexate or biological DMARDs. In patients whose monotherapy failed, combination therapy with synthetic DMARDs improved response rates. Numbers and types of short-term adverse events were similar for biological and synthetic DMARDs. The evidence was insufficient to draw conclusions about differences for rare but serious adverse events for biological DMARDs.

Limitation: Most studies were short-term efficacy trials conducted in selected populations with few comorbid conditions.

Conclusion: Limited available comparative evidence does not support one monotherapy over another for adults with rheumatoid arthritis. Although combination therapy is more effective for patients whose monotherapy fails, the evidence is insufficient to draw firm conclusions about whether one combination or treatment strategy is better than another or is the best treatment for early rheumatoid arthritis.

Editors' Notes Context Which disease-modifying antirheumatic drugs (DMARDs) best reduce symptoms, improve function, and prevent radiographic progression in patients with rheumatoid arthritis? Contribution This systematic review of trials that compared DMARDs in adults with rheumatoid arthritis found few direct comparisons of different agents but no important differences among synthetic DMARDs or anti–tumor necrosis factor drugs. Combination therapy improved response rates and functional outcomes in patients whose monotherapy failed. Numbers and types of short-term adverse events were similar among DMARDs. Implication Of several monotherapies for adults with rheumatoid arthritis, no regimen is clearly superior. Combination therapies improve response rates in some patients previously receiving monotherapy. —The Editors

 

Author and Article Information

From the University of North Carolina and Cecil G. Sheps Center for Health Services Research, Chapel Hill, North Carolina; RTI International, Research Triangle Park, North Carolina; Danube University, Krems, Austria; and Ludwig Boltzmann Institute for Health Technology Assessments, Vienna, Austria.

Disclaimer: The authors of this report are responsible for its contents. The findings and conclusions do not necessarily represent the views of the Agency for Healthcare Research and Quality. Therefore, no statement in this report should be construed as an official position of the Agency for Healthcare Research and Quality or of the U.S. Department of Health and Human Services.

Acknowledgment: The authors thank Timothy Carey, MD, MPH, of the University of North Carolina at Chapel Hill for his insightful comments on the report.

Grant Support: Contract no. 290-02-0016 from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, to RTI International.

Potential Financial Conflicts of Interest: Honoraria: B.L. Jonas (Abbott).

Requests for Single Reprints: Katrina E. Donahue, MD, MPH, Department of Family Medicine, University of North Carolina at Chapel Hill, CB #7595, 590 Manning Drive, Chapel Hill, NC 27599-7595.

Dr. Gartlehner: Ludwig Boltzmann Institute for Health Technology Assessments, Garnisongasse 7, 1090 Vienna, Austria.

Dr. D. Jonas, Ms. Thieda, and Ms. Morgan: Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, 725 Martin Luther King Jr. Boulevard, CB #7590, Chapel Hill, NC 27599.

Ms. Lux and Dr. Lohr: RTI International, 3040 Cornwallis Road, PO Box 12194, Research Triangle Park, NC, 27709.

Dr. B. Jonas: Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, CB #7280, 3330 Thurston Building, Chapel Hill, NC 27599.

Dr. Hansen: School of Pharmacy, University of North Carolina at Chapel Hill, 2205 Kerr Hall, CB #7360, Chapel Hill, NC 27599.

Read all Rapid Responses

The Uncertainty of Effective Treatment for RA May Lie with the Investigators

Stephanie M Lacson, et al.

Annals Online, 30 Nov 2007 [Full text]

Comparative Effectiveness of Biologics to Methotrexate

Tassos Anastassiades, et al.

Annals Online, 13 Dec 2007 [Full text]

Oral Methotrexate Is The Way to Go In The Treatment Of RA

Daniel Arkfeld

Annals Online, 25 Jan 2008 [Full text]

Excellent systematic reviews of clinical trials may not be useful for patient care

Theodore Pincus, et al.

Annals Online, 27 May 2008 [Full text]