Active Smoking Associated With Doubled Relapse Rate in MOGAD

Current smoking was significantly associated with increased relapse activity in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), while vascular risk factors showed no association with relapse outcomes, according to a retrospective cohort study published in the Multiple Sclerosis Journal.¹ The findings from the Oxford National Neuromyelitis Optica Service add to a growing body of evidence linking active smoking to worse disease outcomes in MOGAD and strengthen the case for smoking cessation counseling as a standard component of care.

Led by Jacqueline Palace, MD, PhD, Professor of Neurology at the Nuffield Department of Clinical Neurosciences, University of Oxford, the analysis included 172 patients followed over a median 4.1 years from disease onset. Of those with known smoking status (n = 148), 52.7% were never smokers, 31.1% were past smokers, and 16.2% were current smokers. Nearly half the cohort (48.3%) developed a relapsing course over follow-up, with a higher proportion of current smokers among relapsers than non-relapsers (26.1% vs 7.6%; P = .005).

For the primary outcome of annualized relapse rate, multivariable negative binomial regression confirmed a 2.2-times higher relapse rate in current compared with never smokers after adjustment for age at onset, sex, onset attack phenotype, acute steroid use, and immunosuppressive treatment (adjusted rate ratio, 2.23; 95% CI, 1.35 to 3.68; P = .0017). Crucially, relapse rate was not significantly different between past and never smokers (adjusted rate ratio, 0.81; 95% CI, 0.51 to 1.29; P = .38), suggesting that the elevated risk associated with active smoking may be reversible upon cessation.

For time-to-relapsing course, multivariable Cox regression did not identify a statistically significant association with smoking status, though univariable analysis showed a consistent directional trend toward shorter time-to-relapse in current versus never smokers (hazard ratio, 1.76; 95% CI, 0.97 to 3.22; P = .06). The authors noted the discordance between relapse rate and time-to-relapse outcomes is likely attributable to differences in statistical power, as relapse rate captures the cumulative effect of smoking across the entire follow-up period.

Neither the presence of any non-smoking vascular risk factor (hypertension, hypercholesterolaemia, type 2 diabetes, or elevated BMI) nor individual vascular comorbidities were significantly associated with relapse risk or rate on any analysis. The most prevalent non-smoking vascular risk factor was elevated BMI, present in 27.9% of the cohort, but numbers for individual comorbidities were small, limiting the ability to detect effects at the level of specific risk factors.

READ MORE:

To date, the biological mechanism linking smoking to increased MOGAD relapse activity is not established. In the study, the investigators highlighted that smoking elevates circulating pro-inflammatory cytokines including interleukin-6 and C-reactive protein, and noted the reported effectiveness of anti-IL-6 receptor therapies in case series of highly relapsing MOGAD as a potential mechanistic connection worth investigating. A 2024 Nature study by Saint-Andre and colleagues demonstrated that smoking induces innate immune changes that reverse upon cessation, while adaptive immune modifications can persist due to epigenetic reprogramming, a finding the authors proposed may help explain why past smokers showed similar relapse rates to never smokers in this cohort.²

This analysis builds directly on prior work from the same Oxford group. A 2025 study in Multiple Sclerosis Journal examining 236 MOGAD patients found that current smokers had significantly lower odds of good disability recovery after the onset attack compared with never smokers, and a prior smaller study found current and past smokers had higher risk of MRI lesion persistence following attacks.³ Together, these datasets present a consistent picture of active smoking as a detrimental modifier of MOGAD disease activity across multiple outcome dimensions.

Several limitations apply. Smoking status was self-reported and collected at a single time point, with no data on pack-year history or changes during follow-up. The small current smoker group (n = 24) limits precision in the primary analysis. Confounding from unmeasured variables cannot be excluded, and the specialized service setting may have introduced selection bias toward more relapsing disease.

REFERENCES
1. Yeh WZ, Chan F, Francis A, et al. Myelin oligodendrocyte glycoprotein antibody-associated disease and relapse risk: effects of smoking and vascular risk factors. Mult Scler J. 2026;32(8):794-805. doi:10.1177/13524585261429292. https://doi.org/10.1177/13524585261429292
2. Saint-Andre V, Charbit B, Biton A, et al. Smoking changes adaptive immunity with persistent effects. Nature. 2024;626(8000):827-835. doi:10.1038/s41586-023-06968-8. https://doi.org/10.1038/s41586-023-06968-8
3. Chan F, Berhanu D, Samadzadeh S, et al. Smoking status and vascular risk factors as predictors of disability in AQP4-NMOSD and MOGAD. Mult Scler. 2025;31:658-667. doi:10.1177/13524585251325069. https://doi.org/10.1177/13524585251325069