Efficacy and Safety of Edaravone in Amyotrophic Lateral Sclerosis: It is Safe but Does Not Stop Progression.

Background: Edaravone is recommended for amyotrophic lateral sclerosis (ALS) based on a study showing an effect on a defined subset of patients.

Aim: To document the effect of edaravone in a cohort of ALS patients from India to find out if, after starting edaravone, there is a plateau period or significant slowing from baseline to compare results with existing literature.

Methods: This was a single-center, prospective observational study with no control arm (due to ethical reasons). ALS patients >18 years of age, not requiring respiratory support or tube feeding, were included. All patients were given edaravone infusion in addition to standard of care and oral riluzole 50 mg twice daily. This consisted of giving the drug in monthly cycles over 6 months. The first cycle consisted of daily infusion of the drug for 14 days followed by a drug-free interval for the remaining part of the month. From cycle 2 to cycle 6, the patients received the drug for the first 10 days of the month followed by a drug-free interval for the remaining part of the month. The primary outcome was a significant change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score from baseline at 6 months. Secondary outcomes were monthly change in ALSFRS-R scores when compared with the previous month and baseline, change in the first 3 months compared to the change in the next 3 months, adverse drug effects, and number of deaths. The study was registered with the Indian Council of Medical Research Clinical Trial Registry of India with the trial number CTRI/2019/11/021838. Paired t-test was used for statistical analysis.

Results: Thirty patients received the drug along with riluzole. Twenty-three patients completed all six monthly infusions. Two died (3 months), two developed adverse reactions (3 months) and did not want further infusions (one had breathing difficulty and the other had hypotension during infusion). Two withdrew consent due to perceived poor effectiveness of the drug. The mean ALSFRS-R at baseline was 35.17 [standard deviation (SD) 8.01; range 20-46]. The primary outcome showed a significant decline in the mean last available ALSFRS-R score 6 months by -4.9 (SD 1.21) (p < 0.01). For the secondary outcome measure, mean monthly ALSFRS-R score was calculated before each infusion after excluding dropouts. There was a significant monthly decline in ALSFRS-R score: -0.93 (SD 0.58), -1.0 (-0.52), -0.90 (SD 0.71), -0.87 (SD 0.61), -0.82 (SD 0.57), -0.95 (SD 0.63), respectively (p < 0.001). There was also a progressive monthly decline when compared to baseline. The rate of decline in the first 3 months was the same as in the remaining 3 months: -2.5 (SD 0.73) vs -2.6 (SD 0.98) (p = 0.3).

Conclusion: Edaravone infusion does not stop or significantly slow progression of disease from baseline but is safe.