title: Biological agents in polyarticular juvenile idiopathic arthritis: A meta-analysis of randomized withdrawal trials.
abstract: Although various biological agents are in use for polyarticular juvenile idiopathic arthritis (pJIA), head-to-head trials comparing the efficacy and safety among them are lacking. We aimed to compare the efficacy and safety of biological agents in pJIA using all currently available randomized withdrawal trials (wRCTs).
  
  
  
  A systematic search of MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov was performed. Eligible wRCTs: patients with pJIA where a biological agent was compared with another biological agent or placebo. Efficacy was evaluated using disease flare as a measure. Adverse events (AEs) and serious AEs were evaluated. Network meta-analysis compared biological agents based on a (empirical Bayes) mixed-effects logistic regression model that combines statistical inference from both direct and indirect comparisons of the treatment effects between biological agents.
  
  
  
  Of 496 references identified, five wRCTs were included-abatacept, adalimumab, anakinra, etanercept, and tocilizumab, one trial each, all vs. placebo. There were no differences in efficacy among biological agents and most showed statistically significant efficacy compared with placebo (nearly all exceptions were in agreement with the original study data). Serious AEs occurred very infrequently (0-8%) and an analysis was not possible. There were no differences for AEs when compared among biological agents or to placebo.
  
  
  
  There were no statistical differences among biological agents for efficacy or safety. Overall, biological agents were effective and safe when compared to placebo. Based on these data, other considerations such as price and availability may need to be used to decide among biological agents when treating pJIA patients.
authors.affiliation: Pediatric Rheumatology Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; (b)Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Amarilyo
authors.affiliation: Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Tarp
authors.affiliation: Hamburger Zentrum für Kinder und Jugendrheumatologie, Klinikum Eilbek, Hamburg, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Foeldvari
authors.affiliation: Department of Pediatrics, Tel Aviv Sourasky Medical Center, Dana Dwek Children's Hospital, Tel Aviv, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Cohen
authors.affiliation: David Geffen School of Medicine, University of California, 1000 Veteran Ave Rm 32-59, Los Angeles, CA 90025.
authors.forename: Tracy D
authors.initials: TD
authors.lastname: Pope
authors.affiliation: David Geffen School of Medicine, University of California, 1000 Veteran Ave Rm 32-59, Los Angeles, CA 90025.
authors.forename: Jennifer M P
authors.initials: JM
authors.lastname: Woo
authors.affiliation: Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: Christensen
authors.affiliation: David Geffen School of Medicine, University of California, 1000 Veteran Ave Rm 32-59, Los Angeles, CA 90025. Electronic address: defurst@mednet.ucla.edu.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use; D000068879:Adalimumab / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D001685:Biological Factors / Q000627:therapeutic use*; D000069340:Deprescriptions; D000068800:Etanercept / Q000627:therapeutic use; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001685:Biological Factors; D053590:Interleukin 1 Receptor Antagonist Protein; D000069594:Abatacept; D000068879:Adalimumab; C502936:tocilizumab; D000068800:Etanercept
keywords: juvenile idiopathic arthritis; meta-analysis; randomized withdrawal trials