Safety and Efficacy of Edaravone in Patients with Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-analysis

Abstract

Background and objective: The efficacy and safety of edaravone for the treatment of amyotrophic lateral sclerosis (ALS) remain unclear. The aim of this meta-analysis was to provide evidence-based medical guidance and advice for the clinical application of edaravone in the treatment of ALS.

Methods: PubMed, Embase, Chinese Biomedical Literature Database (CBM), Cochrane Library and Web of Science were searched through 09 March 2022 for randomized controlled trials (RCTs) on the safety and efficacy of edaravone versus placebo during follow-up of patients with ALS. A summary of the outcome measures with GRADE was performed. This study was registered on PROSPERO (ID: CRD 42022319997).

Results: Five RCTs with a total of 566 participants were included, and there was a significant difference (mean difference [MD] 1.33, 95% confidence interval [CI] 0.33-2.34; p = 0.009) in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score between the treatment and placebo groups. The edaravone group had an increased grip strength (MD 0.26, 95% CI 0.03-0.49; p = 0.03) and modified Norris Scale score (MD 2.81, 95% CI 1.18-4.43; p = 0.0007). However, there were no significant differences between groups for the change in forced vital capacity (FVC)% (MD 0.55, 95% CI - 3.15 to 4.24; p = 0.77), pinch strength (MD 0.05, 95% CI - 0.05 to 0.16; p = 0.33) or Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) score (MD - 4.76, 95% CI - 9.56 to 0.03; p = 0.05). The incidence of adverse events (AEs) (risk ratio [RR] 0.09, 95% CI 0.93-1.05; p = 0.65), serious adverse events (SAEs) (RR 0.72, 95% CI 0.52-1.00; p = 0.05) and the number of deaths (risk difference [RD] 0.00, 95% CI - 0.02 to 0.03; p = 0.83) were not statistically different from the placebo group. The quality of evidence was low only for SAEs, and the remaining outcome measures were of moderate quality.

Conclusions: Compared with placebo, edaravone may provide potential clinical benefits in the treatment of ALS and may not increase the number of AEs and deaths. However, due to the low-quality evidence of the included studies and the small sample size, more high-quality and high-standard research evidence is needed to confirm these results.

Protocol registration: This study was registered on PROSPERO (ID: CRD 42022319997).