title: Efficacy of biologic therapy across individual juvenile idiopathic arthritis subtypes: A systematic review.
abstract: To determine the efficacy of differing biologic therapies amongst individual juvenile idiopathic arthritis (JIA) subtypes rather than JIA overall.
  
  
  
  A systematic literature review was conducted between January 1975 and November 2014. Studies included were randomised controlled trials, controlled trials, non-randomised prospective studies or case-control studies. Subjects were required to have a diagnosis of JIA and were ≤20 years of age at study entry. Studies were deemed suitable for inclusion only when the authors reported the efficacy of biologic drugs within individual ILAR subtypes rather than JIA overall.
  
  
  
  Of 7663 articles identified in the original search, 25 were deemed eligible for inclusion in this review. These articles included over 4000 participants classified as having JIA, with mean age groups ranging from 3 to 13 years. Systemic JIA was the largest represented subtype, whilst the persistent oligoarthritis subtype was represented by the lowest number of participants (n = 54). Concerning etanercept, children with extended oligoarticular JIA were more likely to achieve inactive disease than other subtypes, with rheumatoid factor (RF) negative patients achieving inactive disease more frequently than RF positive children. Prospective data showed similar responses to etanercept in persistent oligoarticular groups compared to other subtypes. Etanercept was also shown to be efficacious in ERA and PsA, although the drug was not successfully discontinued in any of these patients without recurrence of the disease. In a study of abatacept, no differences were seen across subtypes. Systemic JIA appeared to be less responsive to etanercept when compared to tocilizumab over 12 weeks (etanercept: ACR30 58-78% and tocilizumab: ACR30 85%). However, longer term response over 12 months was more similar (etanercept: ACR30 83-100% and tocilizumab: ACR30 87-98%).
  
  
  
  This review has provided some evidence of a differing response to individual biologics according to JIA subtype and highlighted the under-representation of certain subtypes in published studies. Comparison of efficacy of individual biologics within subtypes is limited as published studies use variable methodology and head-to-head trials of biologics are lacking. Future trial design should consider differences in treatment response across and within ILAR subtypes to enable clinicians to make more relevant treatment decisions and achieve better patient outcomes.
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Davies
authors.affiliation: Department of Rheumatology, Tameside Hospital NHS Foundation Trust, Ashton-under-Lyne, UK.
authors.forename: Danielle
authors.initials: D
authors.lastname: Gaynor
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Kimme L
authors.initials: KL
authors.lastname: Hyrich
authors.affiliation: Department of Paediatric Rheumatology, Alder Hey Children׳s NHS Foundation Trust, Eaton Rd, Liverpool L12 2AP, UK. Electronic address: clare.pain@alderhey.nhs.uk.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Pain
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use; D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D000068800:Etanercept / Q000627:therapeutic use; D006801:Humans; D008297:Male; D064887:Observational Studies as Topic; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D000069594:Abatacept; C502936:tocilizumab; D000068800:Etanercept
keywords: Biologic therapies; Efficacy; Juvenile idiopathic arthritis; Systematic review