title: Efficacy and safety of biological agents for systemic juvenile idiopathic arthritis: a systematic review and meta-analysis of randomized trials.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Musculoskeletal Statistics Unit, Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Tarp
authors.affiliation: Pediatric Rheumatology Unit, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Amarilyo
authors.affiliation: Hamburger Zentrum für Kinder- und Jugend Rheumatologie, Klinikum Eilbek, Hamburg, Germany and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Foeldvari
authors.affiliation: Musculoskeletal Statistics Unit, Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: Christensen
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Jennifer M P
authors.initials: JM
authors.lastname: Woo
authors.affiliation: Pediatric Rheumatology Unit, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Cohen
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Tracy D
authors.initials: TD
authors.lastname: Pope
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA defurst@mednet.ucla.edu.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D053590:Interleukin 1 Receptor Antagonist Protein; D011993:Recombinant Fusion Proteins; C541220:canakinumab; C531377:rilonacept; C502936:tocilizumab
keywords: biological agents; meta-analysis; randomized controlled trials; systematic review; systemic juvenile idiopathic arthritis