Riluzole is used in the management of amyotrophic lateral sclerosis (ALS, Lou Gehrig disease, Dejerine-type Charcot syndrome) and is designated an orphan drug by the US Food and Drug Administration (FDA) for use in this condition. The current indication is based principally on 2 double-blind, placebo-controlled trials in patients with either familial or sporadic ALS who had a disease duration of less than 5 years and a baseline forced vital capacity (FVC) of 60% or greater. In these trials, the time to death or insertion of a tracheostomy in patients receiving riluzole for at least 1 year (maximum of 18 months) was prolonged compared with that in placebo recipients.
In the first placebo-controlled trial, survival benefit with riluzole therapy occurred principally in patients with bulbar- versus limb-onset ALS, possibly an artifact of the small sample size; site of disease onset did not influence survival benefit in the second, larger trial. Differences in survival in both trials were observed early in treatment and diminished thereafter; mortality at the end of the studies was not significantly different between the treatment and placebo groups. In the first trial in 155 patients, 57 of 77 patients (74%) receiving riluzole 100 mg daily (50 mg twice daily) were alive at 12 months compared with 45 of 78 patients (58%) receiving placebo. Survival benefit was attributable almost entirely to increased survival in patients with bulbar-onset ALS; 1-year survival rates with riluzole and placebo were 73 and 35%, respectively, in patients with bulbar-onset disease, compared with 74 and 64%, respectively, in patients with limb-onset disease. In the second placebo-controlled trial in 959 patients, which included a dose-ranging evaluation, 1-year survival was prolonged in patients receiving riluzole 100 or 200 mg daily (50 or 100 mg twice daily, respectively) but not in those receiving 50 mg daily (25 mg twice daily); survival was similar with the 100- and 200-mg daily dosages. Muscle strength and neurologic function did not improve with riluzole therapy in these trials, although in the first trial a slower rate of deterioration in muscle strength was observed.