The effects of intervention with intravenous edaravone in Study 19 on hospitalization, tracheostomy, ventilation, and death in patients with amyotrophic lateral sclerosis

Abstract Introduction/Aims Intravenous (IV) edaravone is a US Food and Drug Administration–approved treatment for amyotrophic lateral sclerosis (ALS), shown in clinical trials to slow physical functional decline. In this study we compared the effect of IV edaravone (edaravone‐first group) versus placebo followed by IV edaravone (placebo‐first group) on survival and additional milestone events. Methods This work is a post hoc analysis of Study 19/MCI186‐19, which was a randomized, placebo‐controlled, phase 3 study investigating IV edaravone versus placebo. Study 19 and its 24‐week extension have been described previously (NCT01492686). Edaravone‐first versus placebo‐first group time to events for specific milestone(s) were analyzed post hoc. Time‐to‐event composite endpoints were time to death; time to death, tracheostomy, or permanent assisted ventilation (PAV); and time to death, tracheostomy, PAV, or hospitalization. Results The risk for death, tracheostomy, PAV, or hospitalization was 53% lower among patients in the edaravone‐first vs placebo‐first groups (hazard ratio = 0.47 [95% confidence interval 0.25 to 0.88], P = .02). The overall effect of IV edaravone on ALS progression could be seen in the significant separation of time‐to‐event curves for time to death, tracheostomy, PAV, or hospitalization. ALS survival composite endpoint analyses (ALS/SURV) suggested a treatment benefit (least‐squares mean difference) for the edaravone‐first versus the placebo‐first group at week 24 (0.15 ± 0.05 [95% confidence interval 0.06 to 0.25], P < .01) and week 48 (0.11 ± 0.05 [95% confidence interval 0.02 to 0.21], P = .02). Discussion These analyses illustrate the value of timely and continued IV edaravone treatment, as earlier initiation was associated with a lower risk of death, tracheostomy, PAV, or hospitalization in patients with ALS.