The Comparative Efficacy and Safety of Biologics for the Treatment of Rheumatoid Arthritis: A Systematic Review and Metaanalysis
GERALD GARTLEHNER, RICHARD A. HANSEN, BETH L. JONAS, PATRICIA THIEDA, and KATHLEEN N. LOHR
Objective. Biologics are an important therapeutic option for treating patients with rheumatoid arthritis (RA). However, they are associated with rare but severe adverse events such as serious infections, lymphoma, or chronic heart failure. In addition, dosing regimens and routes of administration differ substantially among biologics. In a systematic review, we assessed the comparative efficacy and safety of biologic agents for RA.
Methods. We searched electronic databases up to May 2006. We limited evidence to controlled trials for efficacy but included observational evidence for safety. Outcomes of interest were clinical response, radiographic progression, and quality of life. Given the paucity of head-to-head evidence, we conducted adjusted, indirect comparisons of placebo-controlled trials.
Results. Twenty-six controlled trials provided efficacy data; 18 additional studies assessed safety. The only evidence directly comparing 2 biologic agents was a nonrandomized, open-label trial that found no differences in effectiveness and safety between etanercept and infliximab. Adjusted indirect comparisons indicate no significant differences in efficacy between anti-tumor necrosis factor (TNF) drugs. However, anti-TNF drugs appear to be more efficacious than anakinra, although not all comparisons reached statistical significance. Because of the lack of sound longterm safety data, evidence is insufficient to draw firm conclusions about the comparative safety of biologics.
Conclusion. Anti-TNF drugs appear to be more efficacious than anakinra but do not differ significantly among each other. Clinical considerations such as comorbidities, route of administration, dosing regimens, and specific side effect profiles may guide the choice of an anti-TNF drug. (First Release Nov 1 2006; J Rheumatol 2006;33:2398-408)
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From the Cecil G. Sheps Center for Health Services; School of Pharmacy, Division of Pharmaceutical Policy and Evaluative Sciences; School of Medicine, Thurston Arthritis Research Center; and School of Public Health, Health Policy and Administration, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Funding for this research was provided to the Cecil G. Sheps Center for Health Services Research through a subcontract with the Center for Evidence-Based Policy, Oregon Health & Science University. Dr. Hansen is supported by grant K12 RR023248.
G. Gartlehner, MD, MPH, Cecil G. Sheps Center for Health Services Research; R.A. Hansen, PhD, RPh, School of Pharmacy, Division of Pharmaceutical Policy and Evaluative Sciences; B.L. Jonas, MD, School of Medicine, Thurston Arthritis Research Center; P. Thieda, MA, Cecil G. Sheps Center for Health Services Research; K.N. Lohr, PhD, School of Public Health, Health Policy and Administration.
Address reprint requests to Dr. G. Gartlehner, Cecil G. Sheps Center for Health Services, University of North Carolina at Chapel HillResearch, 725 Martin Luther King Jr Blvd., Chapel Hill, NC 27599. E-mail: firstname.lastname@example.org
Accepted for publication July 28, 2006.