title: A phase II study of laquinimod in Crohn's disease.
abstract: OBJECTIVE
  Laquinimod is an oral therapeutic agent under investigation for the treatment of Crohn's disease (CD), Huntington's disease, lupus nephritis and multiple sclerosis. This dose escalation study evaluated the safety and efficacy of laquinimod as induction therapy in patients with active moderate-severe CD.
  
  
  METHODS
  Multicentre, double-blind, sequential-cohort, randomised controlled trial with laquinimod doses of 0.5, 1, 1.5 or 2 mg/day or placebo (n=45 per cohort randomised in a 2:1 ratio) for 8 weeks with 4-week follow-up. Stable concomittant therapies and prior use of anti-tumour necrosis factor agents were permitted. Comprehensive safety assessments were performed and efficacy analyses included the proportions of patients in clinical remission (CD Activity Index (CDAI) <150 and no treatment failure (TF)), and with a clinical response (70 or 100 point CDAI reduction from baseline or remission and no TF).
  
  
  RESULTS
  117 patients received laquinimod and 63 patients received placebo. The overall incidence of adverse events (AEs) in the laquinimod group was similar to the pooled placebo group (86.2%-96.7% vs 82.5%) and most AEs were mild to moderate in severity. Treatment with laquinimod 0.5 mg showed consistent effects on remission (48.3% (CI 31% to 66%) vs 15.9% (CI 9% to 27%)), response 100 (55.2% (CI 37% to 71%) vs 31.7% (CI 22% to 44%)) and response 70 (62.1% (CI 44% to 77%) vs 34.9% (CI 24% to 47%)) versus placebo. Laquinimod 1.0 mg showed less benefit (26.7% remission (CI 14% to 44%) and 53.3% response 70 (CI 36% to 70%)), and no effect was noted on remission/response at higher doses.
  
  
  CONCLUSIONS
  Laquinimod was safe and well tolerated, and the effects on remission and response of the 0.5 mg dose suggest a treatment benefit in patients with CD.
  
  
  BACKGROUND
  NCT00737932.
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands University of California San Diego, La Jolla, USA Icahn School of Medicine at Mount Sinai, New York, New York, UK Catholic University of Leuven, Belgium Teva Pharmaceuticals, Frazer, Pennsylvania, USA Teva Pharmaceuticals, Netanya, Israel Formerly Teva Pharmaceuticals, Netanya, Israel Chiasma Pharma, Jerusalem, Israel Robarts Research Institute University of Western Ontario, London, Ontario, Canada.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: University of California San Diego, La Jolla, USA Icahn School of Medicine at Mount Sinai, New York, New York, UK.
authors.forename: Jean Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Catholic University of Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Teva Pharmaceuticals, Frazer, Pennsylvania, USA.
authors.forename: Kurt
authors.initials: K
authors.lastname: Brown
authors.affiliation: Teva Pharmaceuticals, Netanya, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Barkay
authors.affiliation: Teva Pharmaceuticals, Netanya, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Sakov
authors.affiliation: Formerly Teva Pharmaceuticals, Netanya, Israel Chiasma Pharma, Jerusalem, Israel.
authors.forename: Asi
authors.initials: A
authors.lastname: Haviv
authors.affiliation: Robarts Research Institute University of Western Ontario, London, Ontario, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D015363:Quinolones; C476223:laquinimod
keywords: CLINICAL DECISION MAKING; CLINICAL TRIALS; CROHN'S DISEASE; IBD CLINICAL; PHARMACOTHERAPY