A disproportionality analysis of nervous system adverse events associated with disease-modifying therapies in multiple sclerosis: insights from the FDA adverse event reporting system (FAERS).

Abstract

Background: Disease-modifying therapies (DMTs) have significantly improved the management of multiple sclerosis (MS), but their potential nervous system adverse events (AEs) remain a critical concern. This study aims to evaluate the risk of nervous system AEs associated with 11 DMTs using the FDA Adverse Event Reporting System (FAERS) database, following the READUS-PV guidelines.

Methods: We performed a disproportionality analysis on FAERS data from Q1 2004 to Q3 2024, focusing on nervous system AEs related to DMTs, such as Alemtuzumab (AL), Ofatumumab (OF), Ocrelizumab (OC), and Fingolimod (FI). Using disproportionality analysis and Bayesian methods, we identified signals of these AEs. We also conducted subgroup analyses across age, gender, weight, geographic regions, and outcomes to assess AE distribution. In addition, a sensitivity analysis was done to evaluate the consistency of the association between DMTs and nervous system AEs across severities. The time to onset and clinical characteristics of AEs were examined as well.

Results: Among 245,469 nervous system AE reports, Siponimod (SI), Natalizumab (NA), FI, and Teriflunomide (TE) exhibited the highest signal values (ROR > 3.0), with SI showing the strongest association [ROR = 3.44, 95% CI (3.34-3.55)]. Females accounted for 76.0% of nervous system AEs, and severe AEs such as central nervous system lesions (mortality rate: 0.97%) and cognitive disorders (mortality rate: 0.94%) were detected. The median time to onset of AEs varied significantly across DMTs, ranging from 14 days for AL to 816 days for Interferon Beta-1a (IN). Subgroup analyses highlighted variations in AE reporting across different demographics and geographic regions. The sensitivity analysis further confirmed the robustness of our findings, indicating consistent associations between DMTs and severe nervous system AEs.

Conclusions: This study highlights significant differences in the nervous system AEs profiles of DMTs, with SI, NA, FI, and TE showing higher risks of nervous system AEs. These findings underscore the importance of vigilant monitoring and personalized treatment strategies to mitigate nervous system risks in MS patients. Further research is needed to confirm these associations and investigate the mechanisms that underlie them.