title: Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of the interleukin-1 inhibitor rilonacept (interleukin-1 Trap) for gout flare prevention during initiation of uric acid-lowering therapy (ULT).
  
  
  METHODS
  In total, 241 adult patients with gout, ≥2 gout flares within the past year, and a serum urate level ≥7.5 mg/dl were initiated on allopurinol 300 mg daily and randomly allocated in a 1:1:1 ratio to receive 16 once-weekly subcutaneous injections of placebo, rilonacept 80 mg, or rilonacept 160 mg, with a double (loading) dose on day 1. Allopurinol was titrated to achieve a serum urate level of <6.0 mg/dl. The study was powered for the primary efficacy end point, the number of gout flares per patient through week 16.
  
  
  RESULTS
  More patients in the rilonacept groups (80.0% in the rilonacept 80 mg group, 86.4% in the rilonacept 160 mg group) completed the study than in the placebo group (72.5%; P < 0.05 for the rilonacept 160 mg group versus the placebo group). Over 16 weeks, the mean number of gout flares per patient was significantly reduced by rilonacept treatment (placebo: 1.06, rilonacept 80 mg: 0.29 [P < 0.001], rilonacept 160 mg: 0.21 [P < 0.001]). Significantly lower proportions of patients reported ≥1 gout flares with rilonacept 80 mg (18.8%) and rilonacept 160 mg (16.3%) relative to placebo (46.8%; P < 0.001 for both). Except for injection site reactions (1.3% in the placebo group versus 8.8% in the rilonacept 80 mg group [P = 0.0635, post hoc analysis] and 19.8% in the rilonacept 160 mg group [P = 0.0001, post hoc analysis]), the incidence of adverse events was generally balanced among the treatment groups.
  
  
  CONCLUSIONS
  Rilonacept markedly reduced the occurrence of gout flares associated with the initiation of ULT. The efficacy and safety profile suggests that rilonacept may have the potential to improve long-term disease control for some patients by improving adherence to ULT by reducing flares during the first months after ULT initiation.
authors.affiliation: VA Medical Center and University of Pennsylvania, PA 19104, USA. schumacr@mail.med.upenn.edu
authors.forename: H Ralph
authors.initials: HR
authors.lastname: Schumacher
authors.forename: Robert R
authors.initials: RR
authors.lastname: Evans
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Saag
authors.forename: James
authors.initials: J
authors.lastname: Clower
authors.forename: William
authors.initials: W
authors.lastname: Jennings
authors.forename: Steven P
authors.initials: SP
authors.lastname: Weinstein
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Terkeltaub
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006073:Gout / Q000097:blood / Q000188:drug therapy*; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood*
chemical_list: D006074:Gout Suppressants; D010919:Placebos; D011993:Recombinant Fusion Proteins; D014527:Uric Acid; D000493:Allopurinol; C531377:rilonacept