Effects of Vitamin D Supplementation on Disease Activity after a Clinically Isolated Syndrome According to Plasma Vitamin D Levels: Ancillary Analysis of the D-lay MS Randomized Controlled Trial
Manon Rival1, Christophe Demattei2, Lysiane Boulet3, Thibault Mura2, Hanane Agherbi4, Thouvenot Eric1
1IGF, CNRS, INSERM, Univ Montpellier, Service de Neurologie, CHU Nimes, 2Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie (BESPIM), Univ Montpellier, CHU Nimes, 3Laboratoire de Biochimie Hormonale et Nutritionnelle, CHU Grenoble-Alpes, 4Service de Neurologie, CHU Nimes
Objective:

To evaluate the impact of plasma vitamin D (VD) increase on the 24-months risk of disease activity (DA, defined as a relapse and/or MRI activity (new and/or contrast-enhancing lesions)).

Background:
D-lay MS (NCT01817166), a double-blind, placebo-controlled, 24-month, parallel trial in 314 clinically isolated syndrome (CIS) patients across France, showed that oral cholecalciferol (vitamin D3) 100,000 IU every two weeks significantly reduced DA.
Design/Methods:

VD levels were measured centrally by mass spectrometry at baseline and 3 months to reflect the overall change in VD during the study. Groups were compared using a Wilcoxon test. Spearman R correlation coefficient was used for correlations. The effect of VD on DA was analysed using ROC curves and adjusted Cox models.

Results:

266 patients were analyzed (n=140 in the VD group and n=126 in the placebo group) and showed similar median VD levels (52.0 vs. 49.3 nmol/L). In both groups, VD levels at baseline did not predict DA. VD increase at 3 months discriminated DA vs. no DA in the placebo group (median increase 1.6 nmol/L, p=0.036) but not in the VD group (median increase 94.1 nmol/L, p=0.602), where it weakly correlated to patients’ weight (R=-0.22, p=0.031) and to body mass index (BMI, R=-0.37, p<0.001). Combining both groups, VD increase significantly reduced the risk of DA (HR=0.58 for 100 nmol/L increase, p=0.008).

Conclusions:

In line with the global results of D-lay MS, VD increase after supplementation with 100,000 IU cholecalciferol every two weeks significantly reduced the risk of DA at the cohort level. Interestingly, variations of VD levels at 3 months were predictive of DA in the placebo group but not in the VD group, suggesting a maximal effect in this high dosage. Overall, given the excellent safety of VD, these findings suggest that individual adjustment of this high-dose supplementation regimen may be unnecessary.

10.1212/WNL.0000000000216162
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