title: Placebo-controlled trial of oral laquinimod for multiple sclerosis.
abstract: BACKGROUND
  Two proof-of-concept clinical trials have provided evidence that laquinimod reduces disease activity in patients with relapsing-remitting multiple sclerosis.
  
  
  METHODS
  We conducted a randomized, double-blind, phase 3 study at 139 sites in 24 countries. A total of 1106 patients with relapsing-remitting multiple sclerosis were randomly assigned in a 1:1 ratio to receive oral laquinimod at a dose of 0.6 mg once daily or placebo for 24 months. The primary end point was the annualized relapse rate during the 24-month period. Secondary end points included confirmed disability progression (defined as an increase in the score on the Expanded Disability Status Scale that was sustained for at least 3 months) and the cumulative number of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted magnetic resonance imaging.
  
  
  RESULTS
  Treatment with laquinimod as compared with placebo was associated with a modest reduction in the mean (±SE) annualized relapse rate (0.30±0.02 vs. 0.39±0.03, P=0.002) and with a reduction in the risk of confirmed disability progression (11.1% vs. 15.7%; hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; P=0.01). The mean cumulative numbers of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted images were lower for patients receiving laquinimod than for those receiving placebo (1.33±0.14 vs. 2.12±0.22 and 5.03±0.08 vs. 7.14±0.07, respectively; P<0.001 for both comparisons). Transient elevations in alanine aminotransferase levels to greater than three times the upper limit of the normal range were observed in 24 patients receiving laquinimod (5%) and 8 receiving placebo (2%).
  
  
  CONCLUSIONS
  In this phase 3 study, oral laquinimod administered once daily slowed the progression of disability and reduced the rate of relapse in patients with relapsing-remitting multiple sclerosis. (Funded by Teva Pharmaceutical Industries; ClinicalTrials.gov number, NCT00509145.).
authors.affiliation: Department of Neurology and Institute of Experimental Neurology, Università Vita-Salute San Raffaele, Milan, Italy. comi.giancarlo@hsr.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Douglas
authors.initials: D
authors.lastname: Jeffery
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.forename: Alexey
authors.initials: A
authors.lastname: Boyko
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D003371:Cough / Q000139:chemically induced; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D010146:Pain / Q000139:chemically induced; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D015363:Quinolones; C476223:laquinimod