title: Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis.
abstract: OBJECTIVE
  To determine the long-term safety and efficacy of rilonacept, an anti-interleukin-1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  In patients with systemic JIA, ages 4-20 years, the efficacy of rilonacept was evaluated using 30%, 50%, and 70% levels of improvement according to the adapted American College of Rheumatology (ACR) Pediatric 30, 50, and 70 response criteria, respectively. Efficacy and safety were evaluated during 23 months of open-label treatment (3 phases) after a 4-week, double-blind, placebo-controlled phase. Following double-blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept, patients were eligible to receive open-label treatment at their prior dose, with adjustments. Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity (i.e., decreased levels of D-dimer and myeloid-related proteins [MRPs]) were also evaluated.
  
  
  RESULTS
  Twenty-four patients entered the double-blind study and 23 entered the open-label period. Patients were predominantly white and female, and had a median age of 14.0 years at baseline. No significant differences in efficacy were observed between the rilonacept- and placebo-treated patients during the double-blind phase, but fever and rash completely resolved by month 3 in all patients during the open-label treatment period and did not recur. Adapted ACR Pediatric 30, 50, and 70 response rates at 3 months from the start of the study were 78.3%, 60.9%, and 34.8%, respectively; these responses were generally maintained over the study duration. Levels of D-dimer and MRP-8/MRP-14 dramatically improved during the study, and in 22 of 23 patients, the prednisone dose was decreased or prednisone therapy was discontinued. No serious treatment-related adverse events were observed.
  
  
  CONCLUSIONS
  Sustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in >50% of rilonacept-treated patients over 2 years. Treatment with rilonacept had a substantial steroid-sparing effect and was generally well-tolerated.
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lovell
authors.forename: Edward H
authors.initials: EH
authors.lastname: Giannini
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Reiff
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kimura
authors.forename: Suzanne
authors.initials: S
authors.lastname: Li
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Hashkes
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wallace
authors.forename: Karen B
authors.initials: KB
authors.lastname: Onel
authors.forename: Dirk
authors.initials: D
authors.lastname: Foell
authors.forename: Richard
authors.initials: R
authors.lastname: Wu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Biedermann
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Hamilton
authors.forename: Allen R
authors.initials: AR
authors.lastname: Radin
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D011993:Recombinant Fusion Proteins; C531377:rilonacept