title: Medically Significant Infections Are Increased in Patients With Juvenile Idiopathic Arthritis Treated With Etanercept: Results From the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study.
abstract: OBJECTIVE
  The association between anti-tumor necrosis factor therapy and increased rates of infection is widely documented in adults with rheumatoid arthritis. Findings in children with juvenile idiopathic arthritis (JIA) have been less well documented. The aims of this analysis were to compare the rates of medically significant infections (MSIs) in children with JIA treated with etanercept (ETN) versus methotrexate (MTX) and to compare the rates between combination therapy with ETN plus MTX and monotherapy with ETN.
  
  
  METHODS
  A total of 852 ETN-treated children and 260 MTX-treated children had been recruited to the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN). MSIs included infections that resulted in death or hospitalization or were deemed medically significant by the clinician. This on-drug analysis followed the patients until the first MSI, treatment discontinuation, the last followup, or death. Cox proportional hazards models, which were adjusted using propensity deciles, were used to compare rates of MSI between cohorts. Sensitivity analyses were conducted specifically with regard to serious infections (SIs), which were defined as those requiring hospitalization or treatment with intravenous antibiotics/antivirals.
  
  
  RESULTS
  The ETN-treated cohort was older and had a longer disease duration, but the disease activity was similar between the cohorts. A total of 133 first MSIs were reported (109 with ETN and 24 with MTX). Patients receiving ETN had higher rates of MSI than did the controls (propensity decile adjusted hazard ratio 2.13 [95% confidence interval 1.22-3.74]). The risk of MSI was higher whether patients were receiving combination or monotherapy. Sensitivity analysis showed no between-group difference in the rate of SIs, which were much less common.
  
  
  CONCLUSIONS
  ETN therapy is associated with an increased risk of MSI; however, this increased risk disappears when considering only SIs, which suggests that either there were differences in the severity of infections and/or there was a possible reporting bias.
authors.affiliation: University of Manchester and Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Davies
authors.affiliation: University of Birmingham and Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Taunton R
authors.initials: TR
authors.lastname: Southwood
authors.affiliation: University of Manchester and Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Lianne
authors.initials: L
authors.lastname: Kearsley-Fleet
authors.affiliation: University of Manchester and Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Lunt
authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: Kimme L
authors.initials: KL
authors.lastname: Hyrich
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D001424:Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D000068800:Etanercept; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D014777:Virus Diseases / Q000188:drug therapy / Q000453:epidemiology*
chemical_list: D000900:Anti-Bacterial Agents; D018501:Antirheumatic Agents; D000998:Antiviral Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept; D008727:Methotrexate