Smoking Linked to Worse Outcomes in RRMS Patients After 10 Years

Smoking is associated with lower brain volume, more brain lesions, and greater disability and attention deficits among people with relapsing-remitting multiple sclerosis (RRMS) after 10 years, according to a study in Norway.

“The findings imply that patients should be advised and offered aid in smoking cessation shortly after diagnosis, to prevent long-term disability progression,” the researchers wrote.

The study, “The Effect of Smoking on Long-term Gray Matter Atrophy and Clinical Disability in Patients with Relapsing-Remitting Multiple Sclerosis,” was published in the journal Neurology: Neuroimmunology and Neuroinflammation.

Numerous studies have identified smoking as a risk factor for MS development and progression, linking smoking to a greater disability, a higher likelihood of developing a progressive disease course, greater relapse rates, more inflammatory brain lesions, and brain volume loss.

But not all studies have observed such associations, leaving the true relationship obscured.

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To better understand the potential link, researchers evaluated the long-term effects of smoking in MS patients by assessing MRI data and clinical outcomes 10 years later. The analyses included a total of 85 RRMS patients who had participated in the two-year OFAMS Phase 2/3 clinical trial (NCT00360906).

At the trial’s start, all participants had signs of recent inflammatory disease activity and had not received any prior treatment. They were given the approved therapy Rebif (interferon-beta 1a) for the past 1.5 years of the two-year trial, after which they received routine treatment.

Ten years after the trial concluded, 85 of the 87 available participants returned for a follow-up visit.

During the trial, participants’ smoking status was evaluated in two ways: blood levels of cotinine — a byproduct of nicotine that reflects recent tobacco use — and retrospective patient self-reporting.

Since people exposed to smokeless tobacco (such as snuff) can have high cotinine levels, patients reporting the use of smokeless tobacco at the 10-year follow-up visit, but no smoking during that decade, were deemed nonsmokers.

In the self-reporting method, patients answered a questionnaire about habits of tobacco use 10 years after the completion of the OFAMS study. Those reporting regular smoking within the past 10 years were defined as smokers, while those not reporting regular smoking or reporting only snuff use were defined as nonsmokers.

“Samples available for cotinine analyses were missing for one patient, and another patient did not complete the questionnaire concerning tobacco use, leaving 84 patients to be classified as smoker or nonsmoker by each definition,” the researchers wrote.

Based on cotinine levels, 47 people were considered smokers and 37 were deemed nonsmokers during the initial trial. According to self-reporting at follow-up, 48 participants were regular smokers (47 of whom said they also smoked at the time of trial) and 36 were nonsmokers.

At the 10-year follow-up visit, the mean age of smokers, classified with either method, was 49.7 years and that of nonsmokers was 49.4 years.

Results showed that after 10 years, smokers had significantly lower volumes of white matter and deep gray matter and larger total lesion volumes, compared with nonsmokers — regardless of the method used to define smokers. The brain’s white matter mainly consists of nerve fibers, while gray matter is mainly made of nerve cells’ bodies.

These smokers also had worse walking ability, as assessed by the timed 25-foot walk test, and greater declines in attention scores, measured through the paced auditory serial addition test, since the end of the initial trial.

A final statistical analysis adjusted the results taking into account potential influencing factors, such as age, sex, cardiovascular risk factors, disability, and time from diagnosis.

Its results showed that cotinine-based smoking was associated significantly with lower white matter volume and higher brain lesion volumes after 10 years. Patient-reported smoking also was significantly linked to smaller white and gray matter volumes, as well as worse walking ability, and greater attention declines.

“These findings suggest that smoking has a negative long-term influence on prognosis and disease progression in patients with MS,” the researchers wrote.

Since attention is commonly affected by MS, and has been reported to be impaired in smoking non-MS populations, MS patients who smoke may be at a higher “risk of developing cognitive impairment, through mechanisms specific to both MS and smoking,” they added.

These patients “should be advised and offered aid in smoking cessation as early as possible in the disease course,” the researchers wrote.

Given that the study assessed only cotinine levels during the two-year trial, and imaging and clinical outcomes after 10 years, larger studies analyzing these outcomes over time are needed to better understand the effect of smoking duration and cessation in disease progression.