Title : Riluzole for ALS: A meta-analysis of reconstructed Kaplan–Meier curves
Abstract:
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder with limited therapeutic options. Riluzole, the first drug approved for ALS treatment, has shown modest benefits in survival across randomized controlled trials (RCTs). This study aimed to apply a novel statistical approach—reconstruction of Kaplan–Meier (KM) curves— which addresses key limitations of secondary analyses of survival data, including potential biases in meta-analyses based solely on aggregated summary statistics. Analysis included 395 riluzole-treated (100mg per day) and 406 placebo-treated patients from three randomized clinical trials. Individual patient data were reconstructed from published KM curves using the IPDfromKM algorithm and pooled for survival analysis. Log-rank testing demonstrated a statistically significant difference between the riluzole and control groups (P = 0.014). Cox regression confirmed a reduced risk of death or tracheostomy with riluzole (HR 0.78, 95% CI [0.65–0.94], P = 0.0139). The event rate was also significantly lower in the riluzole group (50.4%) compared with controls (58.1%) (P = 0.03). The survival benefit remains limited since the median survival time was 16.8 months for riluzole compared with 14.5 months for placebo. To our knowledge, this is the first reconstructed Kaplan–Meier meta-analysis examining the efficacy of riluzole in prolonging survival in ALS patients. These findings support riluzole as an effective intervention that modestly prolongs survival in ALS, reaffirm its role as the current standard of care, and highlight the potential value of reconstructed KM methods in evaluating therapies with small and heterogeneous trial data.
