title: A phase II, multicenter, open-label study evaluating dosing and preliminary safety and efficacy of canakinumab in systemic juvenile idiopathic arthritis with active systemic features.
abstract: OBJECTIVE
  To assess dosing, preliminary safety, and efficacy of canakinumab, a fully human anti-interleukin-1β (anti-IL-1β) antibody, in children with systemic juvenile idiopathic arthritis (JIA) and active systemic features.
  
  
  METHODS
  In this phase II, multicenter, open-label, dosage-escalation study, children with systemic JIA who were ≥4 years of age, had fever, and were receiving ≤0.4 mg/kg/day of corticosteroids were administered a single subcutaneous dose of canakinumab, 0.5-9 mg/kg of body weight, and were redosed upon relapse. Response to treatment was assessed according to an adaptation of the American College of Rheumatology (ACR) pediatric criteria for improvement.
  
  
  RESULTS
  A total of 23 children ages 4-19 years with active disease were enrolled. Of these, 1 patient was excluded from analysis, and 3 of the reenrolled patients were included twice in the efficacy analysis. By day 15 of the first treatment cycle, 15 of 25 patients (60%) had achieved an adapted ACR Pediatric 50 response, with 4 of them achieving inactive disease status. Response was sustained over time, with 11 of 13 patients able to maintain their response throughout the study. In 8 of the 11 responders who had been receiving steroids at baseline, the steroid dosage was decreased from a mean of 0.38 mg/kg/day to 0.13 mg/kg/day over the first 5 months, and 4 of them were able to discontinue steroids. At a dose of 4 mg/kg of canakinumab given subcutaneously every 4 weeks, the median percentage of patients predicted to relapse within 4 weeks was estimated to be 6% (95% confidence interval 1-21). Therapy was generally well tolerated and few patients experienced injection-site reactions.
  
  
  CONCLUSIONS
  Canakinumab has a promising preliminary safety and efficacy profile in this limited cohort. Based on the findings of this trial, further studies in a larger population of children with systemic JIA are warranted.
authors.affiliation: IRCCS G. Gaslini, Genoa, Italy. nicolaruperto@ospedale-gaslini.ge.it
authors.forename: Nicolino
authors.initials: N
authors.lastname: Ruperto
authors.forename: Pierre
authors.initials: P
authors.lastname: Quartier
authors.forename: Nico
authors.initials: N
authors.lastname: Wulffraat
authors.forename: Patricia
authors.initials: P
authors.lastname: Woo
authors.forename: Angelo
authors.initials: A
authors.lastname: Ravelli
authors.forename: Richard
authors.initials: R
authors.lastname: Mouy
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
authors.forename: Sebastiaan J
authors.initials: SJ
authors.lastname: Vastert
authors.forename: Emanuele
authors.initials: E
authors.lastname: Noseda
authors.forename: Daniele
authors.initials: D
authors.lastname: D'Ambrosio
authors.forename: Jean
authors.initials: J
authors.lastname: Lecot
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.forename: Andrea
authors.initials: A
authors.lastname: Chioato
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008297:Male; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D053583:Interleukin-1beta; C541220:canakinumab