Vitamin D as a Predictor of Functional Deficits in Multiple Sclerosis (P4.014)

OBJECTIVE: To examine the relationship between 25(OH)D early in disease course and MS progression over 5 years using the Multiple Sclerosis Functional Composite (MSFC). BACKGROUND: Higher levels of vitamin D are associated with lower MS clinical and MRI activity, but their relation to clinical outcomes has been less consistent. DESIGN/METHODS: The BENEFIT study evaluated the impact of early versus delayed interferon beta-1b (IFNB-1b) treatment in patients with a first event suggestive of MS (CIS). Serum 25(OH)D concentrations were measured at baseline, 6, 12, and 24 months. 465/468 patients had at least one 25(OH)D measurement. We calculated a season-adjusted 25(OH)D and characterized the 25(OH)D status using a time-dependent cumulative average. MSFC was measured at baseline, months 2, 3, and 6, and every 6 months thereafter. We assessed the relation between 25(OH)D and the MSFC Z-score or its components. Analyses were adjusted for age, sex, treatment, baseline T2 lesions, and CIS onset type (multifocal vs. monofocal). RESULTS: Average 25(OH)D levels were associated with higher MSFC Z-scores. 50 nmol/L increments were associated with a mean 0.29 higher MSFC Z-score (95[percnt] CI: 0.16-0.41, P<0.0001). Similar results were observed using quintiles, where the mean MSFC Z-score was 0.21 (0.10-0.33, P=0.002) higher among individuals in the highest quintile [median 25(OH)D level of 73.2 nmol/L] than those in the lowest [median 25(OH)D level of 28.9nmol/L]. Similarly, for each of the component MSFC tests, the highest quintile of 25(OH)D had better scores than those in the lowest quintile (for PASAT-3: Quintile 5 vs. Quintile 1: 1.18 95[percnt] CI: 0.23-2.12; P=0.03; for 9-hole peg test: Quintile 5 vs. Quintile 1: -1.04 95[percnt] CI: -1.50 - -0.51; P<0.001; timed 25-foot walk: Quintile 5 vs. Quintile 1: -0.32 95[percnt] CI: -0.66-0.03, P=0.05). CONCLUSIONS: These results support the prognostic importance of vitamin D in patients with relapsing remitting MS treated with IFNB-1b. Study Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Dr. Fitzgerald has nothing to disclose. Dr. Munger has nothing to disclose. Dr. Freedman has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Chugai, EMD Canada, Genzyme, Novartis, Sanofi-Aventis, and Teva Canada Innovation. Dr. Hartung has holds stock and/or stock options from Opexa Therapeutics. Prof. Miller has received honoraria through payments to his employer, UCL Institute of Neurology, for Advisory Committee and/or Consultancy advice in multiple sclerosis studies from Biogen Idec,;, Dr. Montalban has received personal compensation for activities with Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall. Dr. Edan has received personal compensation for activities with LFB, Biogenidec, speaking from Serono, Inc., Sanofi, Teva, and Bayer Pharmaceuticals Corporation as a consultant and/or scientific advisory board member. Dr. Barkhof has received personal compensation for activities with Bayer Schering Pharma, Sanofi, Genzyme, Biogen Idec, Teva, Merck Serono, Novartis, Roche, Synthon BV, and Janssen Research as a consultant. Dr. Sandbrink has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Sandbrink holds stock and/or stock options in Bayer Pharmaceuticals Corporation. Dr. Kappos has received personal compensation for activities with Actelion Pharmaceuticals. Dr. Suarez has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Pohl has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Pohl owns stock and/or stock options in Bayer Pharmaceuticals Corporation. Dr. Ascherio has received personal compensation for activities with Almirall, Roche, Sanofi-Aventis, and Serono as a speaker.