Use of biologics in rheumatoid arthritis: current and emerging paradigms of care

Abstract

Background: Improved understanding of rheumatoid arthritis (RA) pathogenesis has led to the development of new biologic treatments that target specific elements of RA inflammatory response.

Objective: Our aim was to provide a comprehensive review of biologic therapies currently used for the treatment of RA.

Methods: A search of MEDLINE (up to October 2010) was conducted. Preference for article inclusion was given to English language meta-analyses and large, Phase III, randomized controlled trials (RCTs) of biologic treatments in patients with RA.

Results: In large RCTs, significantly more patients treated with tumor necrosis factor-α (TNF-α) antagonists (as monotherapy, or as an adjunct to methotrexate) versus controls (35%-67% vs 9%-33% of patients; P ≤ 0.01) achieved an American College of Rheumatology 20 response as a primary study end point. However, safety concerns-especially the potential for serious infections and malignancy-remain for TNF-α blockade. For example, 1 meta-analysis (>5000 patients) reported a 2-fold increase (95% CI, 1.3-3.1) in the risk of serious infections and a 3.3-fold increase (95% CI, 1.2-9.1) in the risk of malignancy. Abatacept and rituximab (given in combination with methotrexate) may be useful clinical alternatives for RA patients with an inadequate response to TNF-α antagonists. These agents do not appear to increase the risk of serious infections (OR, 1.35-1.45; 95% CI, 0.56-3.73), although rituximab may rarely cause progressive multifocal leukoencephalopathy (0.4 cases per 100,000 hospitalizations).

Conclusions: Over the last decade, targeted biologic agents have transformed RA treatment. Although relatively expensive in the short term, the direct costs of these biologics may be offset by slowed disease progression and significant improvements in RA symptoms, physical function, and quality of life.