Supplemental appendix: Randomised trial of daily high-dose vitamin D3 in RRMS patients receiving sc interferon beta-1a

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.