High-Dose Vitamin D Curbs Disease Activity in Early Multiple Sclerosis

High-dose oral cholecalciferol (vitamin D3) supplementation significantly reduced disease activity in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) in the randomized, controlled D-Lay MS trial.

“Combined with data from previous studies on vitamin D as an add-on therapy, the results of the D-Lay MS trial, which show a stronger effect of vitamin D in patients with vitamin D deficiency compared to others, strongly suggest that patients with vitamin D deficiency should be supplemented, regardless of whether they are already under disease-modifying therapy,” Eric Thouvenot, MD, PhD, University Hospital of Nimes, Neurology Department, Nîmes, France, told Medscape Medical News.

The study was published online on March 10 in JAMA. 

Significant Reduction in Disease Activity

Vitamin D deficiency has been implicated in the pathogenesis and activity of MS. Previous studies investigating vitamin D supplementation in MS have shown mixed results.

The D-Lay MS trial included 303 untreated patients with newly diagnosed with CIS (within 90 days), serum 25-hydroxy vitamin D concentration < 100 nmol/L at baseline, and diagnostic MRI meeting 2010 criteria for dissemination in space or two or more lesions and presence of oligoclonal bands. Participants had a median age of 34 years, and 70% were women.

Participants were randomly allocated (1:1) to oral cholecalciferol 100,000 IU or placebo every 2 weeks for 24 months. The primary outcome was the occurrence of disease activity — relapse, new or enlarging T2 lesions, and presence of contrast-enhancing lesions.

During 24 months of follow up, disease activity (relapse and/or MRI activity) occurred in 60.3% of the vitamin D group vs 74.1% of the placebo group (hazard ratio [HR], 0.66; P = .004). The median time to disease activity was longer in the vitamin D group (432 vs 224 days; P = .003).

All three secondary MRI outcome measures favored vitamin D over placebo: 

• MRI activity: 57.1% vs 65.3% (HR, 0.71; P = .02).
• New lesions: 46.2% vs 59.2% (HR, 0.61; P = .003)
• Contrast-enhancing lesions: 18.6% vs 34.0% (HR, 0.47; P = .001)

There was no significant difference between the vitamin D group and the placebo group in clinical relapses (17.9% vs 21.8%; HR, 0.69; P = .16). Patients with severe vitamin D deficiency (< 30 nmol/L) benefited the most from vitamin D supplementation.

High-dose vitamin D supplementation had a favorable safety profile and was well-tolerated. Adverse events were comparable between the groups (17 in the vitamin D group [none related to vitamin D] and 13 in the placebo group), with no severe toxicity or hypercalcemia being reported.

D-Lay MS is “the largest study analyzing the effects of high-dose vitamin D supplementation on disease activity in untreated early MS. It reveals a significant reduction in disease activity, comparable to some available drugs, with excellent safety. This constitutes a real proof of efficacy in MS,” said Thouvenot.

Of note, the efficacy of vitamin D was similar between patients with CIS with or without optic neuritis, “extending its potential target population to all CIS phenotypes,” the investigators wrote.

“Altogether, this suggests that cholecalciferol could represent an inexpensive therapeutic alternative, with low risk of adverse events, after a CIS, especially in populations with limited access to disease-modifying therapies,” they added. 

A New Role for Vitamin D?

F. Perry Wilson, MD, Yale School of Medicine, New Haven, Connecticut, and Medscape’s Impact Factor commentator said the study “remedies” some of the problems with prior studies and “suggests a new role for vitamin D in MS.” 

“The first special fact about this trial” is that they enrolled individuals with CIS, “basically the earliest possible presentation of MS,” Wilson noted.

“The second important difference from some of the prior work is the vitamin D dose. The intervention group in this trial got 100,000 international units of oral cholecalciferol every 2 weeks. This is a big dose,” he noted. 

In terms of the results, Wilson said “an increase in disease activity occurred in 74% of individuals in the placebo group, compared with 60% of individuals in the vitamin D group. That’s a 14% absolute risk reduction, which is fairly impressive.”

Despite several caveats, “it’s hard to look at this trial as anything except a powerful and — to me, at least — unexpected victory for high-dose vitamin D supplementation in early MS,” Wilson concluded.

This study was funded by the French Ministry of Health. Thouvenot reported receiving grants from the French Ministry of Health and the French National Research Agency during the conduct of the study and personal fees from Biogen, Merck, Novartis, Roche, and Sanofi and grants from Biogen, Novartis, France SEP and EDMUS Foundation outside the submitted work. Wilson had no relevant disclosures.