A CONFIRMATORY DOSE-RANGING STUDY OF RILUZOLE IN ALS

ALS is a progressive motor neuron disease with no effective treatment. The anti-excitotoxic drug riluzole (100 mg/day) has been shown to dec rease mortality and muscular deterioration in ALS patients. To confirm and extend the therapeutic effect of riluzole, we performed a double- blind, placebo-controlled, multicenter, international, dose-ranging (5 0, 100, 200 mg/day), stratified study in 959 ALS outpatients treated f or up to 18 months. Primary efficacy criterion was survival and the ef fect of treatment was analyzed before (Wilcoxon and log rank tests) an d after adjustment on prognostic factors (Cox model). Secondary effica cy criterion was disease progression assessed through change in functi onal measures. Tracheostomy-free survival rates were: 50.4% (placebo), 55.3% (50 mg riluzole) (p = 0.23, Wilcoxon test; p = 0.25, log-rank t est), 56.8% (100 mg riluzole) (p = 0.05, Wilcoxon test; p = 0.076, log -rank test), and 57.8% (200 mg riluzole) (p = 0.061, Wilcoxon test; p = 0.075, log-rank test). At the end of the 18-month study, there was a significant dose-related decrease in risk of death or tracheostomy (p = 0.04). Adjustment for baseline prognostic factors showed a 35% decr eased risk of death with the 100-mg dose compared with placebo (p = 0. 002). No significant treatment effects were detected for the functiona l assessments. The most frequent dose-related adverse events included nausea, asthenia, and elevated liver enzyme levels. This study confirm s the therapeutic effect of riluzole in a large representative ALS sam ple, over an 18-month period. Riluzole is well tolerated and decreases the risk of death or tracheostomy in ALS patients.