Katrina E. Donahue, MD, MPH; Gerald Gartlehner, MD, MPH; Daniel E. Jonas, MD, MPH; Linda J. Lux, MPA; Patricia Thieda, MA; Beth L. Jonas, MD; Richard A. Hansen, PhD; Laura C. Morgan, MA; Kathleen N. Lohr, PhD
Donahue KE, Gartlehner G, Jonas DE, Lux LJ, Thieda P, Jonas BL, et al. Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis. Ann Intern Med. 2008;148:124-134. doi: 10.7326/0003-4819-148-2-200801150-00192
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Published: Ann Intern Med. 2008;148(2):124-134.
The comparative effectiveness of rheumatoid arthritis therapies is uncertain.
To compare the benefits and harms of disease-modifying antirheumatic drugs (DMARDs) for adults with rheumatoid arthritis.
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.
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.
Information on study design, interventions, outcomes, and quality were extracted according to a standard protocol.
Head-to-head trials (nÂ = 23), mostly examining synthetic DMARDs, showed no clinically important differences in efficacy among synthetic DMARDs (limited to methotrexate, leflunomide, and sulfasalazine) or among antiâ€“tumor necrosis factor drugs (adalimumab, etanercept, and infliximab). Monotherapy with antiâ€“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.
Most studies were short-term efficacy trials conducted in selected populations with few comorbid conditions.
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.
Which disease-modifying antirheumatic drugs (DMARDs) best reduce symptoms, improve function, and prevent radiographic progression in patients with rheumatoid arthritis?
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.
Of several monotherapies for adults with rheumatoid arthritis, no regimen is clearly superior. Combination therapies improve response rates in some patients previously receiving monotherapy.
Numbers of included articles and included studies differ because some studies have multiple publications. RCT = randomized, controlled trial.
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Rheumatology, High Value Care, Rheumatoid Arthritis.
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