Cholecalciferol supplementation in Relapsing Multiple Sclerosis patients treated with subcutaneous interferon beta-1a: a Randomized Controlled Trial. (S44.004)

Objective: To evaluate the benefit of add-on therapy withVitamin D 3 100 kIU twice monthly over 2 years in relapsing multiplesclerosis (RMS) patients treated with subcutaneous interferon beta-1a 44 μg 3 times weekly. Background: Although hypovitaminosis D is a known riskfactor for developing MS, there is no evidence base supporting Vitamin D (VitD)as a treatment in MS. Design/Methods: Double blind randomized placebo controlled2-year multicenter trial on RMS patients with serum VitD levels ≤ 75nmol/L. The primary endpoint was the annualized relapse rate (ARR). The two principal secondary endpoints were Expanded Disability Status Scale (EDSS) and magnetic resonance imaging parameters. Intention to treat (ITT) and completer selection were considered as primary and secondary, respectively. Results: 129 patients were randomized: 63 in VitD group and 66 in placebo group. A non-significant benefit was found in the VitD group(ARR=0.45) compared with placebo (ARR=0.34) with a RR=0.80 ([0.48, 1.32], p=0.379). On the completers sample (n=45, in both VitD and placebo group,), we identified a higher and significant VitD benefit (RR=0.40, [0.20, 0.81], p=.011) on ARR and a lower count of new or enlarged weighted lesions (RR=0.22, [0.10, 0.49], p Conclusions: Although a strong effect was observed inreducing relapses of 60% on completers (RR=0.40), we failed to find a significant effect of VitD on an ITT basis. In spite of an observed clinically relevant effect size of RR=0.80 (20% reduction in relapse rate), the unexpected low relapse rate in the control group (ARR=0.34) underpowered the study. A more thorough statistical analysis of this trial is on the way. Study Supported by: The study is sponsored by Merck, France, an affiliate of Merck KGaA, Darmstadt, Germany. Disclosure: Dr. Camu has received personal compensation for activities with Actelion, Biogen-Idec, Merck Serono, Novartis and Sanofi in the form of honoraria or research grants. Dr. Pierrot-Deseilligny has received personal compensation for activities with Merck, Novartis, and Schering as a speaker. Dr. Hautecoeur has received personal compensation from Merck, Bayer, Biogen, Genzyme and Novartis as a consultant. Dr. Besserve has received personal compensation for activities with Merck as an employee. Dr. Deleglise has received personal compensation for activities with Merck France as an employee. Dr. Lehert has received personal compensation for activities with Merck as a statistical consultant. Dr. Souberbielle has received personal compensation for activities with DiaSorin, Roche Diagnostics, Abbott, Amgen, Shire, MSD, Lilly and Rottapharmaceuticals.