Riluzole Prolongs Survival in Late-Stage Amyotrophic Lateral Sclerosis
Riluzole’s late-stage benefit poses some challenges to health economics, as health care costs are greater in late-stage ALS than in earlier stages.
Riluzole is associated with prolonged survival in patients in the last clinical stage of amyotrophic lateral sclerosis (ALS), according to study findings published in Lancet Neurology.
Investigators retrospectively analyzed patients with probable or definite ALS from a riluzole dose-ranging study who were enrolled between December 1992 and November 1993 using electronic case record forms. A total of 959 patients with ALS from the original study were included in this analysis. Participants were assigned to either 50 mg/day riluzole (n=237), 100 mg/day riluzole (n=236), 200 mg/day riluzole (n=244), or daily placebo (n=242).
All participants were categorized into stage 1 (involvement of 1 domain), stage 2 (involvement of 2 domains), stage 3 (involvement of 3 domains), and stage 4 (nutritional failure or substantial respiratory failure) clinical ALS stages based on the King's clinical ALS staging system. No significant differences were observed between treatment groups in regard to participants' clinical stage at enrollment (P =.22).
Patients who received 100 mg/day riluzole spent significantly more time in stage 4 than patients who were randomly assigned to placebo (hazard ratio [HR] 0.55; 95% CI, 0.36-0.83; log-rank P =.037). A multistate outcome analysis of treatments demonstrated that participants who received higher doses of riluzole experienced a greater mean number of days in stage 4 compared with the placebo arm (226 days [95% CI, 215-237] vs 198 days [95% CI, 186-209], respectively). Similar findings were observed when investigators stratified patients by ALS stage at enrollment as well as when investigators combined treatment groups (HR 0.638; 95% CI, 0.464-0.878; P =.006). No significant differences were observed between the riluzole and placebo arms with regard to time from stages 2 (P =.83) or 3 (P =.88) to stages 4 or 5.
Considering these patient data were obtained from a study that commenced in the early 1990s, the findings may be limited by the less-stringent ALS study criteria used in this time period. In addition, the clinical stage of ALS in these participants were retrospectively estimated and could not be conclusively validated by the investigators.
The investigators suggested that the timing of riluzole benefit “has implications for health economics because the later stages of ALS are associated with higher costs than earlier stages, and therefore prolonging stage 4 is more costly than prolonging stages 1 or 2.”
Fang T, Al Khleifat A, Meurgey JH, et al. Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study [published online March 7, 2018]. Lancet Neurol. doi:10.1016/S1474-4422(18)30054-1