Timing of Riluzole's Mortality Benefit in Amyotrophic Lateral Sclerosis

In the trials leading to approval of riluzole use for patients with amyotrophic lateral sclerosis, survival was extended an average of 3 months, but at what disease stage this benefit occurred has been unknown. Researchers have now conducted a retrospective analysis of the original dose-ranging trial by staging the 959 patients at study entry and following disease progression from stages 2 to 4 according to the ALS Staging System developed at King's College. In stages 2 or 3, disease involves 2 or 3 of the bulbar, upper limb, and lower limb domains, whereas stage 4 corresponds to nutritional failure (10% of premorbid weight loss because of dysphagia) or substantial respiratory failure (requiring noninvasive ventilation). As there were not enough stage 1 patients (early disease; one affected domain) due to the inclusion criteria, the authors could not study this group of patients.

The new analysis shows that the placebo and three riluzole groups (50 mg/day, 100 mg/day, and 200 mg/day) separated in stage 4; i.e., riluzole prolonged the last stage of ALS before death in a dose-dependent manner, with no apparent prolongation of stages 2 or 3.