title: Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions.
abstract: OBJECTIVE
  Gouty arthritis patients for whom non-steroidal anti-inflammatory drugs and colchicine are inappropriate have limited treatment options. Canakinumab, an anti-interleukin-1β monoclonal antibody, may be an option for such patients. The authors assessed the efficacy/safety of one dose of canakinumab 150 mg (n=230) or triamcinolone acetonide (TA) 40 mg (n=226) at baseline and upon a new flare in frequently flaring patients contraindicated for, intolerant of, or unresponsive to non-steroidal anti-inflammatory drugs and/or colchicine. Core study co-primary endpoints were pain intensity 72 h postdose (0-100 mm visual analogue scale and time to first new flare.
  
  
  METHODS
  Two 12-week randomised, multicentre, active-controlled, double-blind, parallel-group core studies with double-blind 12-week extensions (response in acute flare and in prevention of episodes of re-flare in gout (β-RELIEVED and β-RELIEVED-II)).
  
  
  RESULTS
  82.6% patients had comorbidities. Mean 72-h visual analogue scale pain score was lower with canakinumab (25.0 mm vs 35.7 mm; difference, -10.7 mm; 95% CI -15.4 to -6.0; p<0.0001), with significantly less physician-assessed tenderness and swelling (ORs=2.16 and 2.74; both p≤0.01) versus TA. Canakinumab significantly delayed time to first new flare, reduced the risk of new flares by 62% versus TA (HR: 0.38; 95% CI 0.26 to 0.57) in the core studies and by 56% (HR: 0.44; 95% CI 0.32 to 0.60; both p≤0.0001) over the entire 24-week period, and decreased median C-reactive protein levels (p≤0.0001 at 72 h and 7 days). Over the 24-week period, adverse events were reported in 66.2% (canakinumab) and 52.8% (TA) and serious adverse events were reported in 8.0% (canakinumab) and 3.5% (TA) of patients. Adverse events reported more frequently with canakinumab included infections, low neutrophil count and low platelet count.
  
  
  CONCLUSIONS
  Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA; schlesna@umdnj.edu
authors.forename: Naomi
authors.initials: N
authors.lastname: Schlesinger
authors.forename: Rieke E
authors.initials: RE
authors.lastname: Alten
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardin
authors.forename: H Ralph
authors.initials: HR
authors.lastname: Schumacher
authors.forename: Mark
authors.initials: M
authors.lastname: Bloch
authors.forename: Alberto
authors.initials: A
authors.lastname: Gimona
authors.forename: Gerhard
authors.initials: G
authors.lastname: Krammer
authors.forename: Valda
authors.initials: V
authors.lastname: Murphy
authors.forename: Dominik
authors.initials: D
authors.lastname: Richard
authors.forename: Alexander K
authors.initials: AK
authors.lastname: So
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015210:Arthritis, Gouty / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006074:Gout Suppressants; C541220:canakinumab