Abstract

Abstract:

Background: Riluzole is the only drug approved for the treatment of amyotrophic lateral sclerosis (ALS), but its effectiveness in clinical practice remains controversial (1,2). Although previous studies have suggested that riluzole may prolong patient survival, its actual impact on disease progression is limited (3,4). The results of previous studies have been conditioned by the limited evidence available, but in the last 25 years research has increased, as its effectiveness remains a challenge in the management of ALS (5).

Methods: We searched PubMed, Embase, Web of Science, and Scopus until February 21, 2025, to identify studies comparing riluzole with placebo in patients with ALS. Primary endpoints included 12-month survival, median survival, impaired limb function, impaired bulbar function, asthenia, nausea, abdominal pain, dysphagia, and respiratory distress. Relative risk (RR) and standard mean difference (SMD) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using the I² statistic.

Results: Of the 3,214 studies that our search strategy returned, 4 RCTs, 4 prospective cohorts, and 4 retrospective cohorts were included. The population was 14,828 patients, of whom 8,017 received riluzole and 6,811 placebo. We found a similar median survival in both groups (SMD: 0.07; 95% CI:-0.00, 0.14), as well as similar 12-month survival rates (RR: 1.12; 95% CI: 0.88, 1.42), limb function impairment (RR:1.02; 95% CI: 0.72, 1.44), impaired bulbar

function (RR:1.15; 95% CI: 0.63, 2.12), asthenia (RR:1.64; 95% CI: 0.93, 2.87), nausea

(RR:1.20; 95% CI: 0.41, 3.51), abdominal pain (RR:1.93; 95% CI: 0.52, 7.17), dysphagia

(RR:0.60; 95% CI: 0.33, 1.08), and respiratory distress (RR:0.75; 95% CI: 0.42, 1.36) were found between the two groups.

Conclusion: Although riluzole remains the approved treatment for ALS, its limited impact on survival and disease progression suggests that it is not a definitive solution. The results of the meta-analysis suggest that more effective alternatives need to be explored and research needs to be expanded to improve disease management (6). Further research into new treatments that may offer greater clinical benefit for ALS patients is recommended.