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

High-dose vitamin D reduced disease activity in clinically isolated syndrome (CIS) and in early relapsing-remitting multiple sclerosis (MS), the D-Lay MS clinical trial showed.

Over 24 months of follow-up, disease activity occurred in 60.3% of the group taking 100,000 IU oral cholecalciferol (vitamin D3) every 2 weeks and 74.1% of the placebo group (HR 0.66, 95% CI 0.50-0.87, P=0.004), reported Eric Thouvenot, MD, PhD, of the Centre Hospitalier Universitaire de Nimes in France, and co-authors.

The median time to disease activity was longer in people taking vitamin D compared with placebo (432 vs 224 days, P=0.003), the researchers reported in JAMA.

All three secondary MRI outcomes favored the vitamin D group:

• MRI activity: HR 0.71 (P=0.02)
• New lesions: HR 0.61 (P=0.003)
• Contrast-enhancing lesions: HR 0.47 (P=0.001)

All 10 secondary clinical outcomes — including relapse — showed no significant difference between the vitamin D group and placebo.

Severe adverse events occurred in 11% of the vitamin D group and 9% of the placebo group; none were related to cholecalciferol.

Vitamin D deficiency is a risk factor for MS and is associated with an increased risk of disease activity. Studies on the benefits of supplementation have provided inconsistent results, especially as an add-on therapy.

“It was important to conduct a large randomized controlled trial to evaluate the efficacy of high-dose cholecalciferol as monotherapy in reducing disease activity in patients with early MS,” Thouvenot noted.

“For the first time, a large study analyzing the effects of high-dose vitamin D supplementation on disease activity in untreated early MS shows significant results,” he told MedPage Today. “Moreover, the effects of vitamin D on reducing disease activity are comparable to those of some available drugs, with excellent safety. This constitutes real proof of efficacy in MS.”

MS often starts with an acute episode involving the central nervous system like optic neuritis or transverse myelitis. This episode, known as CIS, does not always convert to MS.

From 2013 to 2020, the D-Lay MS trial enrolled patients in MS centers in France with CIS based on 2010 McDonald criteria, randomizing 303 participants to 100,000 IU oral cholecalciferol every 2 weeks for 24 months (or until disease activity occurred) or placebo. Patients receiving a disease-modifying therapy were excluded.

One-third of participants had optic neuritis. The median baseline Expanded Disability Status Scale (EDSS) score was 1.0, indicating no disability and minimal signs in one functional system.

The mean age of participants was 34 and 70% were women. Of these, 303 people took at least one dose of the study drug, including 157 in the vitamin D group and 146 in the placebo group.

The primary outcome was disease activity, defined as occurrence of a relapse and/or MRI activity over 24 months of follow-up. Medical visits occurred at 3, 12, and 24 months after baseline and at relapse. At each visit, patients had brain and spinal cord MRI and clinical assessments.

The median vitamin D level at CIS diagnosis was 45 nmol/L, with 22.4% of participants having severe vitamin D deficiency (less than 30 nmol/L). The median time from CIS onset to randomization was 54 days.

Participants who benefited most from vitamin D were those without spinal cord lesions at diagnosis (HR 0.23 vs 0.85, P=0.01), those with severe vitamin D deficiency (HR 0.33 vs 0.78, P=0.03), and with normal BMI at baseline (HR 0.53 vs 0.95, P=0.048).

During the study period, the McDonald criteria for MS diagnosis were updated, allowing relapsing-remitting MS to be diagnosed more rapidly in people with CIS. The researchers analyzed a subset of 247 trial participants who fulfilled the updated 2017 diagnostic criteria for MS before starting treatment and found that results were similar.

Lesion detection was done only at the MRI intervals specified in the trial, which didn’t necessarily correspond to the moment a lesion developed, Thouvenot and co-authors acknowledged. EDSS scores were not measured frequently enough to assess 3- or 6-month confirmed disability accumulation, they pointed out.

Whether the trial population was diverse or representative was unknown because French law precludes collecting race and ethnicity data in this setting, they added.

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