title: Rilonacept for gout flare prevention during initiation of uric acid-lowering therapy: results from the PRESURGE-2 international, phase 3, randomized, placebo-controlled trial.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of IL-1 inhibitor rilonacept (IL-1 Trap) for gout flare (GF) prevention during initiation of uric acid-lowering therapy (ULT) with allopurinol in a multiregional phase 3 clinical trial.
  
  
  METHODS
  Hyperuricaemic adults (n = 248) from South Africa, Germany and Asia with gout and two or more GFs within the past year were initiated on allopurinol and randomized 1:1:1 to once-weekly s.c. treatment with placebo (PBO), rilonacept 80 mg (R80) or rilonacept 160 mg (R160) for 16 weeks. The primary endpoint was the number of GFs per patient through week 16.
  
  
  RESULTS
  The population was predominantly male and racially diverse (white, 53.2%; Asian, 33.1%; black, 13.7%). Across treatments, most patients completed the study (87.8-92.9%). At 16 weeks the mean number of GFs per patient was reduced by 71.3% with R80 (0.35) and by 72.6% with R160 (0.34) relative to PBO (1.23; both P < 0.0001). The proportion of patients without GFs was higher with R80 (74.4%) and R160 (79.5%) than with PBO (43.9%; both P ≤ 0.0001), and the proportions of patients on rilonacept with multiple GFs were significantly lower (P < 0.001). Overall, the incidence of adverse events (AEs) was similar between PBO (61.0%) and rilonacept (65.1%). Injection site reactions, generally mild, were the most frequent AE with rilonacept (1.2% PBO, 12.2% R80 and 17.9% R160); none of these injection site reactions led to withdrawal. There were no study drug-related serious AEs or deaths.
  
  
  CONCLUSIONS
  Rilonacept significantly reduced the occurrence of GFs associated with initiation of ULT, with >70% of patients having no flares, and demonstrated an acceptable safety and tolerability profile.
  
  
  BACKGROUND
  ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00958438.
authors.affiliation: Newtown Clinical Research, Suite 3, Newgate Centre, Jeppe Street, Newtown, Johannesburg, Gauteng, 2113, South Africa. emitha@iburst.co.za
authors.forename: Essack
authors.initials: E
authors.lastname: Mitha
authors.forename: H Ralph
authors.initials: HR
authors.lastname: Schumacher
authors.forename: Leon
authors.initials: L
authors.lastname: Fouche
authors.forename: Shue-Fen
authors.initials: SF
authors.lastname: Luo
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: Shirletta
authors.initials: S
authors.lastname: King-Davis
authors.forename: Robert R
authors.initials: RR
authors.lastname: Evans
mesh_terms: D000328:Adult; D000493:Allopurinol / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006073:Gout / Q000097:blood / Q000517:prevention & control*; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D053573:Receptors, Interleukin-1 Type I / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood
chemical_list: D006074:Gout Suppressants; D053573:Receptors, Interleukin-1 Type I; D011993:Recombinant Fusion Proteins; D014527:Uric Acid; D000493:Allopurinol; C531377:rilonacept
keywords: biologic therapies; clinical trials and methods; crystal arthropathies; cytokines and inflammatory mediators; inflammation