Efficacy and safety of biological agents for systemic juvenile idiopathic arthritis: a systematic review and meta-analysis of randomized trials

Rheumatology (Oxford). 2016 Apr;55(4):669-79. doi: 10.1093/rheumatology/kev382. Epub 2015 Nov 30.


Objective: To define the optimal biologic agent for systemic JIA (sJIA) based on safety and efficacy data from a randomized controlled trial (RCT).

Methods: Through a systematic literature search, sJIA RCTs evaluating biologic agents were identified. The primary efficacy outcome was defined as a 30% improvement according to the modified American College of Rheumatology Paediatric 30 response criteria (JIA ACR30). The primary safety outcome was defined as serious adverse events (SAEs). Outcomes were analysed by pairwise and network meta-analyses. The quality of evidence between biologic agents was assessed by applying the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.

Results: From the 493 citations originally identified, 5 RCTs were eligible for inclusion-one each for anakinra, canakinumab and tocilizumab and two for rilonacept: all vs placebo. While all were effective, the network meta-analysis indicated with low-quality evidence (due to indirect comparison and inconsistency) that rilonacept-treated patients were less likely to respond than those treated with canakinumab [odds ratio (OR) 0.10 (95% CI 0.02, 0.38), P = 0.001] or tocilizumab [OR 0.12 (95% CI 0.03, 0.44), P = 0.001]. Risks of SAEs were similar among the biologic agents (supported by very low-quality evidence) and not different from placebo.

Conclusion: Despite heterogeneous eligibility criteria and study designs across the five studies and different modified JIA ACR30 criteria, this meta-analysis of short-term RCTs presents empirical evidence that canakinumab and tocilizumab are more effective than rilonacept. Biologic agents in sJIA seem safe and comparable with respect to SAE risk in the short term.

Keywords: biological agents; meta-analysis; randomized controlled trials; systematic review; systemic juvenile idiopathic arthritis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Juvenile / drug therapy*
  • Biological Products / adverse effects
  • Biological Products / therapeutic use*
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / adverse effects
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Randomized Controlled Trials as Topic
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Biological Products
  • Interleukin 1 Receptor Antagonist Protein
  • Recombinant Fusion Proteins
  • canakinumab
  • rilonacept
  • tocilizumab