ECTRIMS 2024: High-dose vitamin D can help delay progression to MS
Fewer patients on vitamin D had evidence of disease activity at 2 years in study
Taking high-dose cholecalciferol (vitamin D) as a supplement is safe and can nearly double the time it takes for people with clinically isolated syndrome (CIS), a first manifestation of neurological symptoms suggestive of multiple sclerosis (MS), to experience new disease activity.
That’s according to data from D-Lay-MS (NCT01817166), a Phase 3 clinical study that tested whether a high dose of cholecalciferol (100,000 IU) was safe and could delay the progression from CIS to clinically definite MS.
Eric Thouvenot, MD, PhD, who directed the study at the University Hospital of Nîmes, in France, presented the data at this year’s European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting, which was held Sept. 18-20 online and in person in Copenhagen.
His oral presentation was titled “High-dose cholecalciferol reduces multiple sclerosis disease activity after a clinically isolated syndrome: results of a 24-month placebo-controlled randomized trial (D-Lay-MS).”
MS is caused by the immune system mistakenly launching an attack against the myelin sheath, a protective coating that wraps around nerve cells. While the exact causes of MS aren’t fully understood, low levels of vitamin D may increase the risk of developing the disease and result in more severe disability.
Vitamin D generally fails to prevent disease activity in relapsing-remitting MS
However, vitamin D supplementation, even at high doses, has generally failed to prevent relapses, brain lesions, or disability progression from occurring in people with relapsing-remitting MS, where relapses, periods when existing symptoms worsen or new symptoms appear, are alternated with remissions, when symptoms ease or disappear.
In the study, Thouvenot and other researchers conducted a clinical trial to test if high-dose cholecalciferol, a form of vitamin D that’s also produced naturally by the skin when exposed to sunlight, could delay conversion from CIS to MS.
For people with CIS to be diagnosed with MS, they must show evidence of damage to the myelin sheath that is disseminated in space, meaning damage that affects multiple areas of the brain and spinal cord, and in time, meaning it occurs over multiple points in time.
The study involved 303 adults with a median age of 34, who had experienced an episode of CIS within the previous 90 days, or about three months. Most (70%) were women, and all had low levels of vitamin D.
Importantly, these patients were originally diagnosed with CIS based on older diagnostic criteria that were in place at the start of the trial. However, with the 2017 revision of the McDonald criteria, about 89% would meet the criteria for a diagnosis of relapsing-remitting MS.
As part of the study, participants were randomly assigned to 100,000 IU of cholecalciferol or a placebo, taken every other week for up to two years.
The main goal was to determine differences in the proportion of patients with evidence of disease activity, meaning a relapse, the development of new or enlarging lesions, or the presence of an active inflammatory lesion on MRI scans.
Results showed high-dose cholecalciferol significantly reduced, by 34%, the proportion of patients with evidence of disease activity at two years compared with the placebo (60.3% vs. 74.1%). The median time to experiencing disease activity was also nearly twice as long for patients who took high-dose cholecalciferol (432 vs. 224 days).
Vitamin D led to significant reductions in lesions after 2 years
Looking at the individual components of disease activity, the team found cholecalciferol led to significant reductions in new or enlarging lesions and in inflammatory lesions after two years, but no differences from the placebo were observed for relapses. The supplements also didn’t significantly affect measures of disability, cognition, quality of life, fatigue, anxiety, and depression.
These findings were similar even after the researchers adjusted for factors such as age, sex, and the number of lesions seen on the MRI scans at the start of the study.
Notably, significant reductions in new or enlarging lesions and in active lesions were also observed in the group of patients who would receive a RRMS diagnosis based on the new criteria, suggesting vitamin D supplements are similarly “efficient in early relapsing remitting MS,” Thouvenot said.
Patients who benefited the most from cholecalciferol supplementation were those who had no lesions in the spinal cord, a severe deficiency of vitamin D, and a normal body mass index, which is a measure of body fat based on weight and height, at the start of the study.
High-dose cholecalciferol was safe and well tolerated, with 288 patients (95.1%) completing the study. A total of 33 serious side effects were reported in 30 patients, but none were considered to be related to cholecalciferol supplementation.
“In line with previous studies, high-dose vitamin D supplementation was safe and well tolerated,” Thouvennot said. “Together with the excellent safety profile, these data support high-dose vitamin D supplementation in early MS and make vitamin D the best candidate for add-on therapy evaluation in the therapeutic strategy for MS.”
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