Smoking and disability outcomes in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Smoking is a well-established environmental risk factor for multiple sclerosis (MS), yet its impact on disability progression remains incompletely understood, with conflicting evidence across studies. OBJECTIVE: This review evaluated smoking and clinical outcomes in MS. Disability progression was the primary outcome; disability severity, imaging, relapse recovery, functional status, and patient-reported outcomes were secondary outcomes. METHODS: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception through the 4th of March 2026. RESULTS: Eighteen studies were included. Smoking was not significantly associated with increased EDSS (SMD = 0.09, 95% CI [-0.04; 0.22]) or MSSS (SMD = 0.10, 95% CI [-0.15; 0.36]). Similarly, no significant associations were observed for progression to EDSS ≥4 (HR = 1.27, 95% CI [0.90; 1.81]) or EDSS ≥6 (HR = 1.20, 95% CI [0.65; 2.23]). T2 lesion volume was not significantly associated with smoking under the prespecified random-effects model. Broadly defined disability progression was not significantly associated with smoking, although the estimate was imprecise and heterogeneity was substantial (HR = 1.88, 95% CI [0.82; 4.32]). High heterogeneity was observed across several outcomes. Narrative findings suggested possible associations with poorer quality of life, greater fatigue, respiratory symptoms, and poorer relapse recovery, although these outcomes were heterogeneous and were not direct measures of longitudinal disability progression. CONCLUSION: Smoking was generally associated with trends toward worse clinical outcomes in multiple sclerosis; however, statistically significant effects were not consistently observed across pooled analysis.