title: Association of Vitamin D Levels With Multiple Sclerosis Activity and Progression in Patients Receiving Interferon Beta-1b.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Serum 25(OH)D measurements were performed at baseline, 6 months, and 12 months.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Fitzgerald
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
authors.forename: Kassandra L
authors.initials: KL
authors.lastname: Munger
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Köchert
authors.affiliation: Department of Neurology, University of Chicago, Chicago, Illinois.
authors.forename: Barry G W
authors.initials: BG
authors.lastname: Arnason
authors.affiliation: Department of Neurology, Scientific Institute H. S. Raffaele, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Department of Neurology and Neuroscience, Rutgers-New Jersey Medical School, Newark.
authors.forename: Stuart
authors.initials: S
authors.lastname: Cook
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Goodin
authors.affiliation: Neuroimaging Research Unit, Scientific Institute and University Vita-Salute, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.affiliation: Department of Neurology, University of Dusseldorf, Dusseldorf, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.affiliation: Department of Neurology, Piedmont Health Care, Mooresville, North Carolina.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Jeffery
authors.affiliation: Department of Neurology, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Connor
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, New Jersey.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Suarez
authors.affiliation: Bayer Pharma AG, Berlin, Germany12Bayer Pharma AG, Berlin, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Sandbrink
authors.affiliation: Department of Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Bayer Pharma AG, Berlin, Germany14Department of Neurology, University Hospital Bonn, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Pohl
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts15Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ascherio
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000367:Age Factors; D004185:Disability Evaluation; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D000068576:Interferon beta-1b / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D012189:Retrospective Studies; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D000068576:Interferon beta-1b; C104450:25-hydroxyvitamin D