Efficacy and safety of edaravone in treatment of amyotrophic lateral sclerosis-a systematic review and meta-analysis

Background: Based on the results of randomized, double-blind, placebo-controlled trials, the benefit and safety of edaravone in the treatment of amyotrophic lateral sclerosis remain controversial. We performed a meta-analysis to evaluate the efficacy and safety of edaravone in the treatment of this disease.

Methods: We searched PubMed, the Cochrane Library, and Embase from the inception of electronic data to April 2018. We included randomized, double-blind, placebo-controlled trials reporting amyotrophic lateral sclerosis patients receiving 60-mg intravenous edaravone or intravenous saline placebo for 24 weeks. The primary efficacy evaluation was changed in Amyotrophic Lateral Sclerosis Functional Rating Scale score from baseline to after the trial. Measure of safety was the frequency of investigated adverse events and serious adverse events. Data synthesis and analysis and evaluation of risk of bias were performed using RevMan 5.3 software. Heterogeneity among studies was evaluated with the I² statistic.

Results: A total of 367 patients were analyzed across three randomized controlled trials (183 patients receiving intravenous edaravone; 184 receiving placebo). A difference in ALSFRS-R score between groups at 24 weeks was found (mean difference [MD] = 1.63, 95% confidence interval [CI] 0.26-3.00, P = .02). No differences in the frequency of adverse events (odds ratio [OR] = 1.22, 95% CI 0.68-2.19, P = .50) or serious adverse events (OR = 0.71, 95% CI 0.43-1.19, P = .20) were found.

Conclusion: Intravenous edaravone is efficacious in amyotrophic lateral sclerosis patients, with no severe adverse effects. Additional reliable randomized controlled trials with larger sample sizes will further assess the efficacy and safety of edaravone in amyotrophic lateral sclerosis.

Clinical trial registration: The systematic review and meta-analysis was registered in the international prospective register of systematic reviews. (PROSPERO registration number: CRD42018096191; http://www.crd.york.ac.uk/PROSPERO .).