RT Journal Article SR Electronic T1 Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a JF Neurology JO Neurology FD Lippincott Williams & Wilkins SP e1906 OP e1916 DO 10.1212/WNL.0000000000008445 VO 93 IS 20 A1 Raymond Hupperts A1 Joost Smolders A1 Reinhold Vieth A1 Trygve Holmøy A1 Kurt Marhardt A1 Myriam Schluep A1 Joep Killestein A1 Frederik Barkhof A1 Manolo Beelke A1 Luigi M.E. Grimaldi A1 on behalf of the SOLAR Study Group YR 2019 UL http://n.neurology.org/content/93/20/e1906.abstract AB 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.AE=adverse event; ANCOVA=analysis of covariance; ARR=annualized relapse rate; CI=confidence interval; CUA=combined unique active; DMT=disease-modifying treatment; EDSS=Expanded Disability Status Scale; HR=hazard ratio; IEC=independent ethics committees; IFN-β-1a=interferon-β-1a; ITT=intention-to-treat; MS=multiple sclerosis; NEDA-3=no evidence of disease activity; OR=odds ratio; PBVC=percent brain volume change; RRMS=relapsing-remitting multiple sclerosis; SAE=serious adverse event; SC=subcutaneous; SOLAR=Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting MS Receiving Rebif Treatment; TEAE=treatment-emergent adverse event; TESAE=treatment-emergent serious adverse event