The Efficacy and Safety of Dalfampridine on Cognition and Fatigue in People With Multiple Sclerosis: A Systematic Review and Meta-Analysis

Background: Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system. People with MS frequently experience cognitive dysfunction and fatigue. Dalfampridine (DAL), a potassium channel blocker, is US Food and Drug Administration–approved for the treatment of walking impairment in people with MS. It may also enhance nerve conduction in regions associated with fatigue and cognitive dysfunction. This study aims to evaluate DAL’s efficacy in improving these symptoms, as well as its safety profile, in people with MS. Methods: A systematic search was conducted across MEDLINE, ScienceDirect, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science, covering all records from database inception through April 1, 2024. Randomized controlled trials (RCTs) comparing DAL with placebo in people with MS and reporting impaired cognition and fatigue were included. A random-effects model was used to calculate the risk ratio (RR), standardized mean difference (SMD), and mean difference (MD) with 95% CIs. Results: Of 1329 studies identified, 13 RCTs involving a total of 827 people with MS were included. DAL demonstrated a significant improvement in cognitive symptoms (SMD = 0.21; 95% CI, 0.04-0.38; P = .01; I² = 6%). However, no significant difference was observed between DAL and placebo in reducing fatigue (MD = 3.70; 95% CI, –4.37 to 11.77;P = .37; I² = 19%). Safety measures were comparable, with no significant difference in adverse events (RR = 1.11; 95% CI, 0.99-1.25; P = .08; I² = 0%). Conclusions: People with MS receiving DAL demonstrated significant improvement in cognitive symptoms; however, further studies are warranted to validate and confirm this finding.