Abstract Details

Title Vitamin D and Tobacco Use and Long-Term Clinical and MRI Outcomes among CIS patients: 11-year Follow-up of BENEFIT.

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-003

Objective To unravel effects of vitamin D and smoking in patients with clinically isolated syndrome (CIS) followed over 11 years.

Background Information about long-term effects of vitamin D and smoking on Multiple sclerosis (MS) course is scarce.

Design/Methods We included 277 CIS participants in 11-year follow-up of BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) for whom levels of 25-hydroxy-vitaminD and cotinine (tobacco use) were assessed at baseline, months 6, 12, 24, 54, 60 and 11 year (cotinine only at 6, 12 and 24 months). We used linear mixed effect models to predict the rate of change in EDSS and MSFC between 6-month and 11 years. Further, using linear and logistic regression models, we evaluated whether serum 25-hydroxyvitaminD and cotinine levels measured 6 to 24 months after the CIS contributed to predict MRI outcomes at 11 years.

Results After adjusting for potential confounders, a 50nmol/l increment in 25-hydroxy-vitaminD predicted less disability worsening [ß_{EDSS_increase}=-0.12, 95%CI: -0.22 to -0.02, p=0.02, and ß_{Z_MSFC}=+0.092, 95%CI: 0.005-0.178, p=0.04). Serum 25-hydroxy-vitaminD levels were not overall significantly associated with MRI outcomes, although some results suggested beneficial effects. The odds of having T2 and T1 lesion volumes above the median decreased with increasing 25-hydroxy-vitaminD levels (for T2: OR for a 50 nmol/L increase =0.32, for T1: OR =0.39; p-value=0.1 for both), whereas the odds of having brain volume (OR=3.3, p=0.02) and thalamic volume (OR=2.4, p=0.07) above the median increased with increasing 25-hydroxy-vitaminD levels. Tobacco use was not significantly associated with disability worsening but was related to higher T2 (B=+1454 mm³, p=0.04) and T1 lesion volume (B=+620 mm³, p=0.03]. Smokers displayed non-significantly lower brain and thalamic volumes.

Conclusions Vitamin D elevation and smoking cessation after disease onset might be beneficial for long-term clinical and CNS integrity in MS.

Authors/Disclosures
PRESENTER	No disclosure on file
Kassandra L. Munger (Harvard School of Public Health)	Ms. Munger has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Ms. Munger has received research support from Department of Defense.
Marianna Cortese, MD, PhD (Harvard T.H. Chan School of Public Health)	Dr. Cortese has received personal compensation in the range of $500-$4,999 for serving as a speaker at educational event with Roche.
Frederik Barkhof, MD, PhD (Image Analysis Center)	Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Frederik Barkhof has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Combinostics. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IXICO. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI.
Gilles Edan	Gilles Edan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Gilles Edan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Gilles Edan has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Biogen. Gilles Edan has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck.
	No disclosure on file
Hans-Peter Hartung, MD, FAAN (Heinrich Heine University Medical Faculty)	Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology.
Xavier Montalban, MD, PhD, FAAN (Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia)	The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck/ EMD Serono. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BMS/ Celgene. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/ Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIAL PD. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PeerVoice. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung Biosys. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas BioPharma. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion/ Janssen Pharmaceuticals. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS/ Celgene. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/ EMD Serono. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann-La Roche. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic Therapeutics. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viatris/ Mylan. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. The institution of Dr. Montalban has received research support from Biogen. The institution of Dr. Montalban has received research support from Hoffmann-La Roche. The institution of Dr. Montalban has received research support from Sanofi/ Genzyme. The institution of Dr. Montalban has received research support from Merck/ EMD Serono. The institution of Dr. Montalban has received research support from Novartis. The institution of Dr. Montalban has received research support from Teva Pharmaceuticals. The institution of Dr. Montalban has received research support from Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received research support from BMS/ Celgene.
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	Dr. Kappos has nothing to disclose.
Frederick W. Foley, PhD (Yeshiva University)	No disclosure on file
Iris Katharina Penner, PhD (COGITO Center & Heinrich Heine University, Neurology Dept, Medical Faculty)	The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. The institution of Dr. Penner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Janssen. The institution of Dr. Penner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TEVA. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Penner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Penner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Penner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Penner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene . Dr. Penner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Penner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Penner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck.
Bernhard Hemmer, MD (Technische Universität München)	No disclosure on file
Edward Fox, MD, PhD, FAAN	Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GW Pharmaceuticals. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Fox has received research support from Biogen. The institution of Dr. Fox has received research support from Genentech. The institution of Dr. Fox has received research support from Celgene - BMS. The institution of Dr. Fox has received research support from Chugai. The institution of Dr. Fox has received research support from Novartis. The institution of Dr. Fox has received research support from EMD-Serono. The institution of Dr. Fox has received research support from TG Therapeutics. The institution of Dr. Fox has received research support from AbbVie. The institution of Dr. Fox has received research support from Sanofi Genzyme. The institution of Dr. Fox has received research support from AbbVie.
Sven Schippling (University of Neurology)	No disclosure on file
Eva-Maria Wicklein, MD (Bayer AG)	Dr. Wicklein has received personal compensation for serving as an employee of Bayer AG.
Alberto Ascherio, MD, PhD	Dr. Ascherio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pfizer. Dr. Ascherio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Ascherio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Ascherio has received research support from NIH and US Department of Defense .

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