Randomized trial of daily high-dose Vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a

Raymond Hupperts*, Joost Smolders, SOLAR Study Group, Reinhold Vieth, Trygve Holmøy, Kurt Marhardt, Myriam Schluep, Joep Killestein, Frederik Barkhof, Manolo Beelke, Luigi M.E. Grimaldi

*Corresponding author for this work

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Abstract

Objective In the phase II, randomized, double-blind, placebo-controlled Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Receiving Rebif Treatment (SOLAR) study (NCT01285401), we assessed the efficacy and safety of add-on vitamin D3 in patients with RRMS. Methods Eligible patients with RRMS treated with SC interferon-β-1a (IFN-β-1a) 44 μg 3 times weekly and serum 25(OH)D levels <150 nmol/L were included. From February 15, 2011, to May 11, 2015, 229 patients were included and randomized 1:1 to receive SC IFN-β-1a plus placebo (n = 116) or SC IFN-β-1a plus oral high-dose vitamin D3 14,007 IU/d (n = 113). The revised primary outcome was the proportion of patients with no evidence of disease activity (NEDA-3) at week 48. Results At 48 weeks, 36.3% of patients who received high-dose vitamin D3 had NEDA-3, without a statistically significant difference in NEDA-3 status between groups (placebo 35.3%; odds ratio 0.93; 95% confidence interval [CI] 0.53-1.63; p = 0.80). Compared with placebo, the high-dose vitamin D3 group had better MRI outcomes for combined unique active lesions (incidence rate ratio 0.68; 95% CI 0.52-0.89; p = 0.0045) and change from baseline in total volume of T2 lesions (difference in mean ranks: −0.074; p = 0.035). Conclusions SOLAR did not establish a benefit for high-dose vitamin D3 as add-on to IFN-β-1a, based on the primary outcome of NEDA-3, but findings from exploratory outcomes suggest protective effects on development of new MRI lesions in patients with RRMS. Clinicaltrials.gov identifier NCT01285401. Classification of evidence This study provides Class II evidence that for patients with RRMS treated with SC IFN-β-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.

Original languageEnglish
Pages (from-to)E1906-E1916
JournalNeurology
Volume93
Issue number20
DOIs
Publication statusPublished - 12 Nov 2019
Externally publishedYes

Bibliographical note

Funding Information:
The Article Processing Charge was funded by Merck KGaA, Darmstadt, Germany.

Funding Information:
This study was funded by Merck KGaA, Darmstadt, Germany. Statistical analyses were performed by Jonathan Alsop (Numerus Ltd., Wokingham, UK) and funded by Merck KGaA. Medical writing assistance was provided by Shaun Foley, Ash Dunne, and Simon Lancaster of inScience Communications, Springer Healthcare, Chester, UK, and supported by Merck KGaA, Darmstadt, Germany. F.B. is supported by the NIHR Biomedical Research Center at UCLH.

Publisher Copyright:
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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