Higher Vitamin D Levels in Rituximab-treated MS Patients Linked to Lower Inflammatory Activity, Study Suggests

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by Jonathan Grinstein |

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MS risk and vitamin D

Rituximab-treated multiple sclerosis (MS) patients who take vitamin D supplements have less inflammatory activity, a study reports.

Increased levels of vitamin D were associated with beneficial treatment outcomes, such as better self-perceived health and reduced levels of the inflammation marker C-reactive protein (CRP).

The study, “Inflammatory activity and vitamin D levels in an MS population treated with rituximab,” was published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.

Since 2015, rituximab has been the most commonly used disease-modifying therapy for MS patients in Sweden, despite lacking formal regulatory approval, meaning it is used off-label.

Vitamin D is suggested to have a link with the immune system, and low circulating levels of vitamin D have been associated with an increase of inflammatory activity in MS patients.

At Umeå University Hospital in Sweden, MS patients treated simultaneously with rituximab and vitamin D supplements were found to have less inflammatory activity, suggesting a possible relationship between rituximab-treated MS patients’ vitamin D levels and inflammatory activity.

To further investigate this possibility, researchers at Umeå looked at clinical information on MS patients who had received at least one intravenous (into-the-vein) infusion of either 500 or 1,000 mg of rituximab from March 2008 to March 2015.

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The information was collected from yearly clinical visits, and included data on relapses, disability, side effects, magnetic resonance imaging (MRI), and self-perceived health. Data on laboratory measures, including levels of immune cells associated with inflammation and metabolite 25-hydroxy-vitamin D (which is indicative of vitamin D levels), were also available.

Based on data from 272 MS patients, with a mean follow-up of 43 months, the researchers found that the levels of 25-hydroxy-vitamin D in samples drawn close to MRIs indicating new lesions were lower than the rest — 62 vs. 81 nmol/L. These new lesions could indicate inflammatory activity.

The team also found that higher 25-hydroxy-vitamin D levels were linked to better self-perceived health, and lower levels of the inflammation marker CRP. Levels of 25-hydroxy-vitamin D did not associate with the risk of side effects.

Among all patients, there was no significant change in disability levels as determined by the Expanded Disability Status Scale (EDSS) before rituximab treatment and at the latest follow-up. This was also true if only relapsing-remitting MS patients were analyzed. In patients with secondary progressive MS, there was an increase on EDSS — from 4 to 5.5. The higher the EDSS score, the greater the patient’s disability. In primary progressive MS, there was a similar, but not statistically meaningful, increase in EDSS score — from 3.5 to 6.

“This discrepancy may suggest that the treatment has its effect by way of decreased inflammatory activity and does not affect neurodegenerative mechanisms involved in MS progression,” the researchers said.

Based on the results, the team concluded that “the inflammatory activity in this rituximab-treated MS population that increasingly used vitamin D supplementation was extremely low,” and that “higher 25-hydroxy-vitamin D levels were associated with beneficial outcomes.”

“Future follow-up studies of MS patients on this treatment at Umeå University Hospital will provide important data on these off-label treatments,” they said.

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