The use of biologic response modifiers in polyarticular-course juvenile idiopathic arthritis: A systematic review

Objective: To systematically review the clinical efficacy and safety evidence of biologic drugs used to treat the polyarticular category of juvenile idiopathic arthritis (JIA). Methods: The literature was searched between 2000 and September 2012 for randomized controlled trials (RCTs), non-randomized comparative studies, and non-comparative observational cohort studies. The drugs evaluated included etanercept, infliximab, adalimumab, abatacept, anakinra, and ritixumab. Eligible studies included 20 or more patients with JIA, the majority of whom had polyarticular course disease. Outcomes of interest were disease improvement defined by the American College of Rheumatology criteria for Pediatrics, disease flares, rates of inactive disease, remissions, discontinuations, and adverse events (severe and non-severe). Results: Thirty-seven studies were included, the majority focused on etanercept. Seven RCTs were identified, including one each for etanercept, infliximab, adalimumab, abatacept, and anakinra, and one each looking at etanercept or infliximab as first-line therapies. There was strong evidence to support the efficacy and safety of biologics over the short-term, but a lack of long-term data for treatments other than etanercept. Several high-quality patient registries confirmed the efficacy and safety of etanercept over the long-term. Conclusions: Current evidence shows that a short-term improvement in treatment response is achieved when patients with polyarticular JIA with an inadequate response to conventional treatment are treated with biologics. Long-term effectiveness data, however, are sparse leaving many questions regarding switches between biologics, handling patients that achieve disease remission, and long-term safety. Study designs other than RCTs may be important in understanding the role of biologics in JIA over the long-term. (C) 2013 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 42:597-618