Vitamin D as an early predictor of multiple sclerosis activity and progression.
OBJECTIVE
It remains unclear whether vitamin D insufficiency, which is common in individuals with multiple sclerosis (MS), has an adverse effect on MS outcomes.


OBJECTIVE
To determine whether serum concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, predict disease activity and prognosis in patients with a first event suggestive of MS (clinically isolated syndrome).


METHODS
The Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a randomized trial originally designed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinically isolated syndrome. Serum 25(OH)D concentrations were measured at baseline and 6, 12, and 24 months. A total of 465 of the 468 patients randomized had at least 1 25(OH)D measurement, and 334 patients had them at both the 6- and 12-month (seasonally asynchronous) measurements. Patients were followed up for 5 years clinically and by magnetic resonance imaging.


METHODS
New active lesions, increased T2 lesion volume, and brain volume on magnetic resonance imaging, as well as MS relapses and disability (Expanded Disability Status Scale score).


RESULTS
Higher 25(OH)D levels predicted reduced MS activity and a slower rate of progression. A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels within the first 12 months predicted a 57% lower rate of new active lesions (P < .001), 57% lower relapse rate (P = .03), 25% lower yearly increase in T2 lesion volume (P < .001), and 0.41% lower yearly loss in brain volume (P = .07) from months 12 to 60. Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60. In analyses using dichotomous 25(OH)D levels, values greater than or equal to 50 nmol/L (20 ng/mL) at up to 12 months predicted lower disability (Expanded Disability Status Scale score, -0.17; P = .004) during the subsequent 4 years.


CONCLUSIONS
Among patients with MS mainly treated with interferon beta-1b, low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression.
Harvard School of Public Health, Boston, Massachusetts.
Alberto
A
Ascherio
Harvard School of Public Health, Boston, Massachusetts.
Kassandra L
KL
Munger
University of British Columbia, Vancouver, Canada.
Rick
R
White
Bayer HealthCare, Berlin, Germany.
Karl
K
Köchert
Harvard School of Public Health, Boston, Massachusetts.
Kelly Claire
KC
Simon
VU University Medical Center, Amsterdam, the Netherlands.
Chris H
CH
Polman
Ottawa Hospital Research Institute, Ottawa, Canada.
Mark S
MS
Freedman
Heinrich-Heine Universität, Düsseldorf, Germany.
Hans-Peter
HP
Hartung
University College London Institute of Neurology, London, England.
David H
DH
Miller
Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Xavier
X
Montalbán
CHU-Hôpital Pontchaillou, Rennes, France.
Gilles
G
Edan
VU University Medical Center, Amsterdam, the Netherlands.
Frederik
F
Barkhof
Bayer HealthCare Pharmaceuticals, Montville, New Jersey.
Dirk
D
Pleimes
University Hospital Basel, Basel, Switzerland.
Ernst-Wilhelm
EW
Radü
Bayer HealthCare, Berlin, Germany6Heinrich-Heine Universität, Düsseldorf, Germany.
Rupert
R
Sandbrink
University Hospital Basel, Basel, Switzerland.
Ludwig
L
Kappos
Bayer HealthCare, Berlin, Germany12Department of Neurology, University Hospital of Bonn, Bonn, Germany.
Christoph
C
Pohl
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003711:Demyelinating Diseases / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D015415:Biomarkers; D014807:Vitamin D; C104450:25-hydroxyvitamin D