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Original Investigation |

Effect of Smoking Cessation on Multiple Sclerosis Prognosis

Ryan Ramanujam, PhD1,2; Anna-Karin Hedström, MD3; Ali Manouchehrinia, PhD1; Lars Alfredsson, PhD3,4; Tomas Olsson, MD, PhD1; Matteo Bottai, PhD5; Jan Hillert, MD, PhD1
[+] Author Affiliations
1Department of Clinical Neuroscience, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden
2Department of Mathematics, KTH-Royal Institute of Technology, Stockholm, Sweden
3Institute of Environmental Medicine, Unit of Cardiovascular Epidemiology, Karolinska Institutet, Stockholm, Sweden
4Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
5Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
JAMA Neurol. 2015;72(10):1117-1123. doi:10.1001/jamaneurol.2015.1788.
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Importance  Smoking tobacco is a well-established risk factor for multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system usually characterized by bouts and remissions and typically followed by a secondary progressive (SP) course. However, it is not clear whether smoking after diagnosis is detrimental.

Objective  To determine whether smoking after MS diagnosis is associated with a change in time to SP disease.

Design, Setting, and Participants  Cross-sectional study of patients with prevalent MS who smoked at diagnosis (n = 728) taken from the Genes and Environment in Multiple Sclerosis Study, which consists of patients from the Swedish National MS Registry. The study entrance date was at time of first-year smoking. The study was conducted between November 2008 and December 2011, with patient environmental data collected from November 2009 to March 2011 via questionnaire. Study participants were from all counties in Sweden diagnosed as having MS at the time of the Genes and Environment in Multiple Sclerosis Study and registered in the Swedish National MS Registry. Patients with MS with relapsing-remitting disease course or SP were included. These patients’ conditions were diagnosed according to the McDonald criteria and the patients responded to recruitment letters with detailed questionnaires.

Exposure  Smoking, considered yearly after diagnosis and combined into a time-invariant covariate before diagnosis.

Main Outcomes and Measures  Time to SPMS, measured using an accelerated failure time model, with smoking as a time-varying covariate. Other covariates included sex, age at diagnosis, snuff use, and smoking before diagnosis.

Results  The optimized model illustrated that each additional year of smoking after diagnosis accelerated the time to conversion to SPMS by 4.7% (acceleration factor, 1.047; 95% CI, 1.023-1.072; P < .001). Kaplan-Meier plots demonstrated that those who continued to smoke continuously each year after diagnosis converted to SPMS faster than those who quit smoking, reaching SP disease at 48 and 56 years of age, respectively.

Conclusions and Relevance  This study provides evidence that continued smoking is associated with an acceleration in time to SPMS and that those who quit fare better. Therefore, we propose that patients with MS should be advised to stop smoking once a diagnosis has been made, not only to lessen risks for comorbidities, but also to avoid aggravating MS-related disability.

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Figure 1.
Genes and Environment in Multiple Sclerosis (GEMS) Study Design and Participation

Smokers at diagnosis (n = 728) comprise the main analysis, while continuers and quitters comprise the secondary analysis.

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Figure 2.
Kaplan-Meier Plot of Quitters and Continuers

A Kaplan-Meier plot with the age at conversion to secondary progressive (SP) disease for smokers at diagnosis who quit smoking completely (n = 118) and smokers at diagnosis who smoked continuously (n = 332).

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Figure 3.
Kaplan-Meier Plot of Never Smokers and Ever Smokers

A Kaplan-Meier plot of age at conversion to secondary progressive (SP) disease for never smokers (n = 1012) compared with ever smokers (n = 1346).

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