title: Efficacy and safety of the human anti-IL-1β monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study.
abstract: BACKGROUND
  Canakinumab is a fully human anti-interleukin IL-1beta monoclonal antibody, being investigated for the treatment of rheumatoid arthritis (RA). This multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study investigated the efficacy and safety of canakinumab in patients with active RA despite ongoing therapy at stable doses of methotrexate.
  
  
  METHODS
  Patients were randomized to receive one of four regimens, in addition to methotrexate, for 12 weeks: canakinumab 150 mg subcutaneously (SC) every 4 weeks (q4wk), canakinumab 300 mg SC (2 injections of 150 mg SC) every 2 weeks, a 600 mg intravenous loading dose of canakinumab followed by 300 mg SC every 2 weeks', or placebo SC every 2 weeks.
  
  
  RESULTS
  Among 274 patients with evaluable efficacy data, the percentage of responders according to American College of Rheumatology 50 criteria (the primary endpoint, based on a 28-joint count) was significantly higher with canakinumab 150 mg SC q4wk than with placebo (26.5% vs. 11.4%, respectively; p = 0.028). Compared to placebo, this dosage of canakinumab was also associated with significantly more favorable responses at week 12 with respect to secondary endpoints including the Disease Activity Score 28, scores on the Health Assessment Questionnaire and Functional Assessment of Chronic Illness Therapy-Fatigue, swollen 28-joint count, and patient's and physician's global assessments of disease activity. No safety concerns were raised with canakinumab therapy, particularly with regard to infections. Few injection-site reactions occurred.
  
  
  CONCLUSIONS
  The addition of canakinumab 150 mg SC q4wk improves therapeutic responses among patients who have active RA despite stable treatment with methotrexate.
  
  
  BACKGROUND
  (ClinicalTrials.gov identifier: NCT00784628).
authors: Department of Internal Medicine II, Schlosspark-Klinik Teaching Hospital of the Charité, University Medicine Berlin, Heubnerweg, Berlin 14059, Germany. rieke.alten@schlosspark-klinik.de
authors: Rieke
authors: R
authors: Alten
authors: Juan
authors: J
authors: Gomez-Reino
authors: Patrick
authors: P
authors: Durez
authors: Andre
authors: A
authors: Beaulieu
authors: Anthony
authors: A
authors: Sebba
authors: Gerhard
authors: G
authors: Krammer
authors: Ralph
authors: R
authors: Preiss
authors: Udayasankar
authors: U
authors: Arulmani
authors: Albert
authors: A
authors: Widmer
authors: Xavier
authors: X
authors: Gitton
authors: Herbert
authors: H
authors: Kellner
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007155:Immunologic Factors; D053583:Interleukin-1beta; C541220:canakinumab; D008727:Methotrexate