Disease-Modifying Therapies in Amyotrophic Lateral Sclerosis: A Network Meta-Analysis of Randomized Clinical Trials

Area of Science:

• Neurology
• Clinical Trials
• Pharmacology

Background:

• No head-to-head trials exist comparing riluzole, edaravone, sodium phenylbutyrate and taurursodiol (SPT), and tofersen for amyotrophic lateral sclerosis (ALS).
• Existing treatments for ALS lack direct comparative efficacy data.

Purpose of the Study:

• To conduct a network meta-analysis (NMA) comparing five interventions for amyotrophic lateral sclerosis (ALS).
• To assess the comparative efficacy of riluzole, edaravone, SPT, and tofersen against each other and placebo.

Main Methods:

• A conventional meta-analysis was performed for interventions with at least two studies.
• A network meta-analysis (NMA) was conducted on randomized clinical trials comparing five ALS interventions.
• Included studies: 3 for riluzole, 3 for edaravone, 1 for SPT, and 1 for tofersen.

Main Results:

• 1601 ALS patients were analyzed (1185 intervention, 416 control).
• Riluzole showed a 36% higher survival probability versus placebo (OR: 1.36, p=0.03).
• No significant differences in mortality or ALSFRS-R scores were found between any interventions in the NMA.

Conclusions:

• Riluzole's survival benefit in conventional meta-analysis is noted, but NMA findings are non-significant.
• Differences in outcome measures and patient heterogeneity limit comparisons between ALS interventions.
• Strong recommendations for ALS treatment cannot be made based on current NMA due to limitations.