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

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.

Clinicaltrialsgov 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.

Figure 1. Disposition of all randomized patients

(A) Week 48 subgroup. (B) Week 96 subgroup. AE = adverse event; IFN-β-1a = interferon-β-1a; IMP = investigational medicinal product; SAE = serious adverse event.

Figure 2. Kaplan-Meier plots

Kaplan-Meier plots of (A) time to first confirmed Expanded Disability Status Scale progression up to week 48 and (B) time to first documented relapse up to week 48.