PT  - JOURNAL ARTICLE
AU  - Camu, William
AU  - Lehert, Philippe
AU  - Pierrot-Deseilligny, Charles
AU  - Hautecoeur, Patrick
AU  - Besserve, Anne
AU  - Jean Deleglise, Anne-Sophie
AU  - Payet, Marianne
AU  - Thouvenot, Eric
AU  - Souberbielle, Jean Claude
TI  - Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE)
AID  - 10.1212/NXI.0000000000000597
DP  - 2019 Sep 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e597
VI  - 6
IP  - 5
4099  - http://nn.neurology.org/content/6/5/e597.short
4100  - http://nn.neurology.org/content/6/5/e597.full
SO  - Neurol Neuroimmunol Neuroinflamm2019 Sep 01; 6
AB  - Objective To evaluate the safety and efficacy of cholecalciferol in patients with relapsing-remitting MS (RRMS).Methods In this double-blind, placebo-controlled parallel-group, 2-year study, 181 patients with RRMS were randomized 1:1. Key inclusion criteria were a low serum 25-hydroxy vitamin D (25OHD) concentration (<75 nmol/L), a treatment with interferon beta-1a 44 μg (SC 3 times per week) 4 months ± 2 months before randomization, and at least one documented relapse during the previous 2 years. Patients received high-dose oral cholecalciferol 100,000 IU or placebo every other week for 96 weeks. Primary outcome measure was the change in the annualized relapse rate (ARR) at 96 weeks. Secondary objectives included safety and tolerability of cholecalciferol and efficacy assessments (ARR, MRI parameters, and Expanded Disability Status Scale [EDSS]).Results The primary end point was not met. In patients who completed the 2-year follow-up (45 with cholecalciferol and 45 with placebo), all efficacy parameters favored cholecalciferol with an ARR reduction (p = 0.012), less new hypointense T1-weighted lesions (p = 0.025), a lower volume of hypointense T1-weighted lesions (p = 0.031), and a lower progression of EDSS (p = 0.026). The overall rate of adverse events was well balanced between groups.Conclusions Although the primary end point was not met, these data suggest a potential treatment effect of cholecalciferol in patients with RRMS already treated with interferon beta-1a and low serum 25OHD concentration. Together with the good safety profile, these data support the exploration of cholecalciferol treatment in such patients with RRMS.Clinicaltrials.gov identifier NCT01198132.Classification of evidence This study provides Class II evidence that for patients with RRMS and low serum 25OHD, cholecalciferol did not significantly affect ARRs.25OHD=25-hydroxy vitamin D; ARR=annualized relapse rate; BOCF=Baseline Observed Carried Forward; DRAE=disease-related adverse event; EDSS=Expanded Disability Status Scale; HR=hazard ratio; ITT=intention to treat; NEDA=No Evidence of Disease Activity; PASAT=Paced Auditory Serial Addition Task; RRMS=relapsing-remitting MS; SCTIW=subcutaneously 3 times per week; SDRAE=serious DRAE; TEAE=treatment emergent adverse event; VD=vitamin D; VDCM=mean of VDC