Original article| Volume 70, 104513, February 2023

Effect of smoking on disease activity in multiple sclerosis patients treated with dimethyl fumarate or fingolimod

Published:January 09, 2023DOI:


      • We evaluated the effect of smoking on the efficacy of oral DMDs in MS patients.
      • Current smoking was a risk factor for relapse in MS patients under oral DMDs.
      • Disease course of former-smokers was similar to that of never-smokers.
      • MS patients should be advised to stop smoking even after initiation of oral DMDs.



      In relapsing-remitting multiple sclerosis (RRMS), smoking is a known risk factor for disease susceptibility and disability progression. However, its impact on the efficacy of oral disease-modifying drugs (DMDs) is unclear. Therefore, we initiated a single-center, retrospective, observational study to investigate the relationship between smoking and disease activity in RRMS patients under oral DMDs.


      We retrospectively enrolled RRMS patients who initiated oral DMDs (fingolimod or dimethyl fumarate) at our hospital between January 2012 and December 2019. Clinical data and smoking status at oral DMD initiation were collected up to December 2020. We conducted survival analyses for relapse and any disease activity, defined as relapse or MRI disease activity, among patients with distinct smoking statuses.


      We enrolled 103 RRMS patients under oral DMDs including 19 (18.4%) current smokers at baseline. Proportions of relapses and any disease activity during follow-up were higher in current smokers (relapse: p = 0.040, any disease activity: p = 0.004) and time from initiating oral DMDs to relapse was shorter in current smokers (log-rank test: p = 0.011; Cox proportional hazard analysis: hazard ratio (HR) 2.72 [95% confidence interval (CI) 1.22–6.09], p = 0.015) than in non-smokers. Time from initiating oral DMDs to any disease activity was also shorter in current smokers (log-rank test: p = 0.016; Cox proportional hazard analysis: HR 2.18 [95% CI 1.14–4.19], p = 0.019) than in non-smokers. The survival curves for relapse and any disease activity were not different between the former smoker and never-smoker groups. Multivariate survival analysis showed current smoking was an independent risk factor for relapse or any disease activity after adjusting for covariates (relapse: HR 2.54 [95% CI 1.06–6.10], p = 0.037; any disease activity: HR 3.47 [95% CI 1.27–9.50], p = 0.015).


      Smoking was a risk factor for disease activity in RRMS patients under oral DMD treatment. RRMS patients should be advised to stop smoking even after the initiation of DMDs.



      ARR (annualized relapse rates), CI (confidence intervals), CSF (cerebrospinal fluid), DMD (disease modifying drug), DMF (dimethyl fumarate), EDSS (Kurtzke's expanded disability status scale), FTY (fingolimod), GA (glatiramer acetate), HR (hazard ratio), IFN-β (interferon-beta), IQR (interquartile range), MS (multiple sclerosis), MSSS (multiple sclerosis severity score), NEDA (no evidence of disease activity), NOx (nitrogen oxide), OCBs (oligoclonal IgG bands), PSL (prednisolone), RRMS (relapsing-remitting multiple sclerosis), SPMS (secondary progressive multiple sclerosis)
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