Disease-modifying antirheumatic drugs (DMARDS) in children with juvenile idiopathic arthritis (JIA)

Abstract

Objectives: To summarize the benefits and harms of disease-modifying antirheumatic drugs (DMARDs) compared to conventional treatment (non-steroidal anti-inflammatory drugs [NSAIDs] and/or intra-articular corticosteroids) with or without methotrexate, and of the various DMARDs compared to one another, in children with juvenile idiopathic arthritis (JIA); and to describe selected tools commonly used to measure clinical outcomes associated with JIA.

Data Sources: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews. Additional studies were identified from the review of reference lists.

Review Methods: To evaluate efficacy, we included prospective trials that included a comparator and that lasted for at least 3 months. No comparator was required for reports of adverse events or of the clinical outcome measure tools.

Results: A total of 198 articles were included. There is some evidence that methotrexate is superior to conventional treatment (NSAIDs and/or intra-articular corticosteroids). Among children who have responded to a biologic DMARD, randomized discontinuation trials suggest that continued treatment decreases the risk of having a flare. Although these studies evaluated DMARDs with different mechanisms of action (abatacept, adalimumab, anakinra, etanercept, intravenous immunoglobulin, tocilizumab) and used varying comparators, followup periods, and descriptions of flare, the finding of a reduced risk of flare was precise and consistent. There are few direct comparisons of DMARDs, and insufficient evidence to determine if any specific drug or drug class has greater beneficial effects. Reported rates of adverse events are similar between DMARDs and placebo in nearly all published randomized controlled trials. This review identified 11 incident cases of cancer among several thousand children treated with one or more DMARD. The Childhood Health Assessment Questionnaire (CHAQ) was the most extensively evaluated instrument of those considered. While it demonstrated high reproducibility and internal consistency, it had only moderate correlations with indices of disease activity and quality of life, and poor to moderate responsiveness.

Conclusions: Few data are available to evaluate the comparative effectiveness of either specific DMARDs or general classes of DMARDs. However, based on the overall number, quality, and consistency of studies, there is moderate strength of evidence to support that DMARDs improve symptoms associated with JIA. Limited data suggest that short-term risk of cancer is low. Future trials are needed to evaluate the effectiveness of DMARDs against both conventional therapy and other DMARDs across categories of JIA, and registries are needed to better understand the risks of these drugs.