title: Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study.
abstract: OBJECTIVE
  This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment.
  
  
  METHODS
  In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4×4-weekly doses of canakinumab (50+50+25+25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks.
  
  
  RESULTS
  A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses ≥50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28-0.38, p≤0.0083), and the percentage of patients experiencing ≥1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing ≥1 flare for canakinumab doses ≥50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28-0.36, p≤0.05). The incidence of adverse events was similar across treatment groups.
  
  
  CONCLUSIONS
  Single canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA. schlesna@umdnj.edu
authors.forename: Naomi
authors.initials: N
authors.lastname: Schlesinger
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mysler
authors.forename: Hsiao-Yi
authors.initials: HY
authors.lastname: Lin
authors.forename: Marc
authors.initials: M
authors.lastname: De Meulemeester
authors.forename: Jozef
authors.initials: J
authors.lastname: Rovensky
authors.forename: Udayasankar
authors.initials: U
authors.lastname: Arulmani
authors.forename: Alison
authors.initials: A
authors.lastname: Balfour
authors.forename: Gerhard
authors.initials: G
authors.lastname: Krammer
authors.forename: Peter
authors.initials: P
authors.lastname: Sallstig
authors.forename: Alexander
authors.initials: A
authors.lastname: So
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D015210:Arthritis, Gouty / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D002097:C-Reactive Protein / Q000378:metabolism; D003078:Colchicine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006074:Gout Suppressants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006074:Gout Suppressants; D053583:Interleukin-1beta; C541220:canakinumab; D000493:Allopurinol; D002097:C-Reactive Protein; D003078:Colchicine