A new study suggests oral high-dose cholecalciferol may reduce disease activity in clinically isolated syndrome and in early relapsing-remitting multiple sclerosis.

Vitamin D deficiency is a risk factor for MS and is linked to the risk of disease activity, but data on the benefits of supplementation are conflicting. Researchers in France set out to evaluate the effectiveness of high-dose cholecalciferol in reducing disease activity in patients with CIS typical for MS.

Researchers conducted clinical trials in 36 MS centers in France. Patients were enrolled from July 2013 to December 2020, with a final follow-up in January 2023. Untreated patients with CIS from 18 to 55 years old with CIS duration less than 90 days , serum vitamin D concentration less than 100 nmol/L, and diagnostic magnetic resonance imaging meeting 2010 criteria for dissemination in space or two or more lesions and presence of oligoclonal bands were recruited.

Patients were randomized to receive oral cholecalciferol 100,000 IU or placebo every two weeks for 24 months. The primary outcome measure was disease activity, defined as occurrence of a relapse or MRI activity (new or contrast-enhancing lesions) over 24 months of follow-up, also analyzed as separate secondary outcomes.

Of the 316 participants enrolled and randomized, the primary analysis included 303 patients who took at least one dose of the study drug and the 288 ultimately completed the 24-month trial. Disease activity was observed in 94 patients in the vitamin D group and in 109 patients in the placebo group, and median time to disease activity was longer in the vitamin D group. 

All three secondary MRI outcomes reported significant differences favoring the vitamin D group versus the placebo group – MRI activity, new lesions, and contrast-enhancing lesions. All 10 secondary clinical outcomes showed no significant difference, including relapse, which occurred in 28 patients in the vitamin D group versus 32 in the placebo group. Results were similar in a subset of 247 patients meeting updated 2017 diagnostic criteria for relapsing-remitting MS at treatment initiation. Severe adverse events occurred in 17 patients in the vitamin D group and 13 in the placebo group, none of which were related to cholecalciferol.

The researchers said oral cholecalciferol 100,000 IU every two weeks significantly reduced disease activity in CIS and early relapsing-remitting MS. These results warrant further investigation, including the potential role of pulse high-dose vitamin D as add-on therapy. 

The researchers said the results warrant further investigation, including the potential role of pulse high-dose vitamin D as add-on therapy.

The findings were published in JAMA.