Placebo-Controlled Trial of Oral Laquinimod for Multiple Sclerosis

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.)