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Original Investigation
December 2015

Association of Vitamin D Levels With Multiple Sclerosis Activity and Progression in Patients Receiving Interferon Beta-1b

Author Affiliations
  • 1Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts
  • 2Bayer Pharma AG, Berlin, Germany
  • 3Department of Neurology, University of Chicago, Chicago, Illinois
  • 4Department of Neurology, Scientific Institute H. S. Raffaele, Milan, Italy
  • 5Department of Neurology and Neuroscience, Rutgers–New Jersey Medical School, Newark
  • 6Department of Neurology, University of California, San Francisco
  • 7Neuroimaging Research Unit, Scientific Institute and University Vita-Salute, Milan, Italy
  • 8Department of Neurology, University of Dusseldorf, Dusseldorf, Germany
  • 9Department of Neurology, Piedmont Health Care, Mooresville, North Carolina
  • 10Department of Neurology, St Michael’s Hospital, Toronto, Ontario, Canada
  • 11Bayer HealthCare Pharmaceuticals, Whippany, New Jersey
  • 12Bayer Pharma AG, Berlin, Germany
  • 13Department of Neurology, University Hospital Basel, Basel, Switzerland
  • 14Department of Neurology, University Hospital Bonn, Bonn, Germany
  • 15Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    † Deceased.
JAMA Neurol. 2015;72(12):1458-1465. doi:10.1001/jamaneurol.2015.2742

Importance  Low serum 25-hydroxyvitamin D (25[OH]D) levels are associated with an increased risk of multiple sclerosis (MS) as well as with increased disease activity and rate of progression in clinically isolated syndromes and early MS.

Objective  To assess the association between 25(OH)D and disease course and prognosis in patients with relapsing-remitting MS treated with interferon beta-1b.

Design, Setting, and Participants  We conducted a prospective cohort study assessing 25(OH)D levels and subsequent MS disease course and progression characterized by magnetic resonance imaging (MRI) and clinical end points. The study took place between November 2003 and June 2005; data analysis was performed between June 2013 and December 2014. The study was conducted among participants in the Betaferon Efficacy Yielding Outcomes of a New Dose (BEYOND) study, a large, phase 3, prospective, multicenter, blinded, randomized clinical trial. Patients were monitored for at least 2 years. Clinic visits were scheduled every 3 months, and MRI was performed at baseline and annually thereafter. Eligible patients included 1482 participants randomized to receive 250 μg or 500 μg of interferon-1b with at least 2 measurements of 25(OH)D obtained 6 months apart.

Exposures  Serum 25(OH)D measurements were performed at baseline, 6 months, and 12 months.

Main Outcomes and Measures  Main outcomes included cumulative number of new active lesions (T2 lesions and gadolinium acetate–enhancing lesions), change in normalized brain volume, relapse rate, and progression determined by the Expanded Disability Status Scale (EDSS). Statistical analyses were adjusted for age, sex, randomized treatment, region, disease duration, and baseline EDSS score.

Results  Overall, average 25(OH)D levels in 1482 patients were significantly inversely correlated with the cumulative number of new active lesions between baseline and the last MRI, with a 50.0-nmol/L increase in serum 25(OH)D levels associated with a 31% lower rate of new lesions (relative rate [RR], 0.69; 95% CI, 0.55-0.86; P = .001). The lowest rate of new lesions was observed among patients with 25(OH)D levels greater than 100.0 nmol/L (RR, 0.53; 95% CI, 0.37-0.78; P = .002). No significant associations were found between 25(OH)D levels and change in brain volume, relapse rates, or EDSS scores. Results were consistent following adjustment for HLA-DRB1*15 or vitamin D–binding protein status.

Conclusions and Relevance  Among patients with MS treated with interferon beta-1b, higher 25(OH)D levels were associated with lower rates of MS activity observed on MRI. Results for brain atrophy and clinical progression were more equivocal.