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

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

doi:10.1212/WNL.0000000000008445

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 D-3 in patients with RRMS.

Methods

Eligible patients with RRMS treated with SC interferon-beta-1a (IFN-beta-1a) 44 mu g 3 times weekly and serum 25(OH)D levels

Results

At 48 weeks, 36.3% of patients who received high-dose vitamin D-3 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 D-3 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 D-3 as add-on to IFN-beta-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.

Classification of evidence

This study provides Class II evidence that for patients with RRMS treated with SC IFN-beta-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.

Original language	English
Pages (from-to)	E1906-E1916
Number of pages	11
Journal	Neurology
Volume	93
Issue number	20
DOIs	https://doi.org/10.1212/WNL.0000000000008445
Publication status	Published - 12 Nov 2019

Keywords

MULTIPLE-SCLEROSIS ACTIVITY
DOUBLE-BLIND
25-HYDROXYVITAMIN D
SUPPLEMENTATION
MULTICENTER
CALCIUM
SAFETY
RISK
CHOLECALCIFEROL
PROGRESSION

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10.1212/WNL.0000000000008445Licence: CC BY-NC-ND

Cite this

@article{1806879e3b944053a78152c1786c9b08,

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

abstract = "ObjectiveIn 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 D-3 in patients with RRMS.MethodsEligible patients with RRMS treated with SC interferon-beta-1a (IFN-beta-1a) 44 mu g 3 times weekly and serum 25(OH)D levelsResultsAt 48 weeks, 36.3% of patients who received high-dose vitamin D-3 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 D-3 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).ConclusionsSOLAR did not establish a benefit for high-dose vitamin D-3 as add-on to IFN-beta-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.Classification of evidenceThis study provides Class II evidence that for patients with RRMS treated with SC IFN-beta-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.",

keywords = "MULTIPLE-SCLEROSIS ACTIVITY, DOUBLE-BLIND, 25-HYDROXYVITAMIN D, SUPPLEMENTATION, MULTICENTER, CALCIUM, SAFETY, RISK, CHOLECALCIFEROL, PROGRESSION",

author = "Raymond Hupperts and Joost Smolders and Reinhold Vieth and Trygve Holmoy and Kurt Marhardt and Myriam Schluep and Joep Killestein and Frederik Barkhof and Manolo Beelke and Grimaldi, {Luigi M. E.} and {SOLAR Study Group}",

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 {\textcopyright} 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.",

year = "2019",

month = nov,

day = "12",

doi = "10.1212/WNL.0000000000008445",

language = "English",

volume = "93",

pages = "E1906--E1916",

journal = "Neurology",

issn = "0028-3878",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "20",

}

TY - JOUR

T1 - Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a

AU - Hupperts, Raymond

AU - Smolders, Joost

AU - Vieth, Reinhold

AU - Holmoy, Trygve

AU - Marhardt, Kurt

AU - Schluep, Myriam

AU - Killestein, Joep

AU - Barkhof, Frederik

AU - Beelke, Manolo

AU - Grimaldi, Luigi M. E.

AU - SOLAR Study Group

N1 - 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.

PY - 2019/11/12

Y1 - 2019/11/12

N2 - ObjectiveIn 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 D-3 in patients with RRMS.MethodsEligible patients with RRMS treated with SC interferon-beta-1a (IFN-beta-1a) 44 mu g 3 times weekly and serum 25(OH)D levelsResultsAt 48 weeks, 36.3% of patients who received high-dose vitamin D-3 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 D-3 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).ConclusionsSOLAR did not establish a benefit for high-dose vitamin D-3 as add-on to IFN-beta-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.Classification of evidenceThis study provides Class II evidence that for patients with RRMS treated with SC IFN-beta-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.

AB - ObjectiveIn 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 D-3 in patients with RRMS.MethodsEligible patients with RRMS treated with SC interferon-beta-1a (IFN-beta-1a) 44 mu g 3 times weekly and serum 25(OH)D levelsResultsAt 48 weeks, 36.3% of patients who received high-dose vitamin D-3 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 D-3 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).ConclusionsSOLAR did not establish a benefit for high-dose vitamin D-3 as add-on to IFN-beta-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.Classification of evidenceThis study provides Class II evidence that for patients with RRMS treated with SC IFN-beta-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.

KW - MULTIPLE-SCLEROSIS ACTIVITY

KW - DOUBLE-BLIND

KW - 25-HYDROXYVITAMIN D

KW - SUPPLEMENTATION

KW - MULTICENTER

KW - CALCIUM

KW - SAFETY

KW - RISK

KW - CHOLECALCIFEROL

KW - PROGRESSION

U2 - 10.1212/WNL.0000000000008445

DO - 10.1212/WNL.0000000000008445

M3 - Article

C2 - 31594857

SN - 0028-3878

VL - 93

SP - E1906-E1916

JO - Neurology

JF - Neurology

IS - 20

ER -