Oral Tobacco Use Linked to Slower MS Progression

Oral tobacco use, also known as moist snuff, is associated with slower progression of multiple sclerosis (MS), a new study shows.

“Our finding that snuff use is not associated with worse disease progression indicates that nicotine replacement therapy could be an attractive way to increase the chance of quitting smoking post diagnosis,” the investigators, with first author, Jing Wu, PhD candidate, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, write.

The findings were published in the August issue of the Journal of Neurology, Neurosurgery and Psychiatry.

Changes Over Time

Previous research shows smoking negatively affects MS outcomes in a dose-dependent manner, but the effect of oral tobacco use and passive smoke on the disease has not been examined, the researchers note.

To investigate, the researchers analyzed data from 9089 patients with MS who were participants in two case-control studies from the Swedish MS registry, mean age 37.6 years and 72% female. At baseline, current cigarette smokers had significantly higher Expanded Disability Status Scale (EDSS) scores compared with nonsmokers.

Researchers estimated rate of change over 15 years in MS progression scores. Never smokers and those never exposed to passive smoking served as reference groups.

All analyses controlled for age at diagnosis, sex, disease phenotype, disease duration, baseline EDSS, and use of disease-modifying therapy.

Compared with never smoking, current smoking was associated with an increased risk of clinical disease worsening (CDW) (adjusted hazard ratio [aHR] 1.13; 95% CI 1.06-1.21), of reaching EDSS 3 (aHR 1.21, 95% CI 1.09-1.34), and EDSS 4 (aHR 1.31, 95% CI 1.14-1.51).

In addition, compared with never smokers, current smoking was associated with a higher risk of physical and psychological worsening as determined by the MS Impact Scale-29 (MSIS-29), and worsening cognitive performance measured by the Symbol Digit Modalities Test (SDMT).

The study revealed a dose-dependent relationship between smoking and negative MS-related outcomes.

At baseline, smokers who stopped smoking after diagnosis did not significantly differ in terms of outcomes compared with nonsmokers, suggesting the detrimental influence of smoking declines after quitting.

The association between smoking and more rapid MS progression may involve toxicity to neural tissue, immune suppression, alteration of cytokine balance, and epigenetic modifications, the researchers note, adding lung irritation may be pivotal.

Overall, 61% of participants reported exposure to daily passive smoking prior to diagnosis. Compared with those never exposed to passive smoking, current exposure was associated with an increased risk of developing CDW (aHR 1.21, 95% CI 1.11-1.32), reaching EDSS 3 (aHR 1.59, 95% CI 1.38-1.85), and EDSS 4 (aHR 1.86, 95% CI 1.62-2.13).

Current exposure to passive smoking was also associated with an increased risk of physical and psychological worsening, but not with worsening cognition.

Current snuff use was significantly associated with lower risk of reaching EDSS 4 (aHR 0.73, 95% CI 0.58-0.92), but not CDW or EDSS 3. It was not significantly associated with the risk of worsening health-related quality of life or cognition.

The fact that snuff use was associated with slower disease progression supports the hypothesis that it’s not nicotine itself that explains the relationship between smoking and MS progression but perhaps lung irritation, the researchers speculate.

Snuff’s Risks, Benefits Unclear

Commenting on the findings, Salim Chahin, MD, associate professor of neurology, John L. Trotter MS Center, Department of Neurology, Washington University, St. Louis, said the study “adds to our knowledge that both active and passive smoking negatively affects people with MS.”

The fact that many patients continued to smoke after their MS diagnosis suggests “more can be done to educate people with MS on the risk of smoking on their disease,” he said.

While snuff was associated with slower disability progression, Chahin said studies are needed to better understand this relationship and the possible role of nicotine agonists in MS disease course.

Chahin said he will continue to recommend smoking cessation to his MS patients and not recommend snuff use as a nicotine replacement therapy because its risks and benefits have not been fully explored.

The study was supported by the Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Swedish Brain Foundation; Swedish Medical Research Council; Margaretha af Ugglas Foundation; Swedish Foundation for MS Research; and NEURO Sweden.

Wu and Chahin report no relevant financial relationships.

JNNP. Published in August 2023.  Full text.

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