Amyotrophic Lateral Sclerosis
Riluzole is used in the management of amyotrophic lateral sclerosis (ALS) and has been designated an orphan drug by the FDA for use in this condition.
ALS (i.e., Lou Gehrig disease, Charcot sclerosis) is a fatal, progressive neurodegenerative disease affecting both upper and lower motor neurons; manifestations include gradual weakness and atrophy in limb, thoracic, abdominal, and bulbar muscles with related deficits in activities of daily living. Some patients also experience mood, cognitive (e.g., frontotemporal dementia), or behavioral changes. Typically, the disease is fatal within 2-5 years of clinical onset, often as a result of respiratory failure. There is no cure for ALS and treatment options are limited. Riluzole has been shown to slow disease progression and prolong survival to a modest degree (e.g., by about 2-3 months); because of this possible benefit, experts recommend that the drug should be offered to patients with ALS. Other interventions (e.g., noninvasive ventilation, percutaneous gastrotomy [PEG]) also should be considered for symptomatic treatment of the disease. Management of ALS requires a multidisciplinary approach to address patients' physical deficits (e.g., loss of mobility, respiratory failure, dysarthria, dysphagia) as well as their social and psychological needs.
The current indication for riluzole is based principally on 2 double-blind, placebo-controlled studies in patients with familial or sporadic ALS (probable or definite) who had a disease duration of less than 5 years and a baseline forced vital capacity (FVC) of 60% or greater. In these studies, 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 study, 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 study. Differences in survival in both studies 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 study 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 study in 959 patients, which included a dose-ranging evaluation, the probability of survival at the end of the study was greater in patients receiving riluzole 100 mg daily (50 mg twice daily) compared with those receiving placebo; survival was not substantially different between the 50-mg daily dosage and placebo, or between the 100- and 200-mg daily dosages. Median survival was prolonged by approximately 60-90 days with riluzole in these studies. Muscle strength and neurologic function did not improve with riluzole therapy in these studies, although in the first study a slower rate of deterioration in muscle strength was observed.