Relationship between vitamin D and interferon beta-1b in the treatment of multiple sclerosis

This article is based on the review “Treatment of Multiple Sclerosis – Relationship between Vitamin D and Interferon beta-1b” by Bruce Taylor, Harold Moses, Friedemann Paul, Gustavo Suarez and Mark Rametta, which was published in the journal, the European Neurological Review, in 2015. DOI: http://doi.org/10.17925/ENR.2015.10.02.124

Vitamin D deficiency is associated with the risk of developing multiple sclerosis (MS) and may also be linked with MS disease activity and progression of disease. In a large study of patients with MS, the benefits of interferon beta-1b treatment were explored. The study, called BENEFIT*, also looked at how vitamin D deficiency influenced the course of disease in the long-term. BENEFIT included 464 patients who had experienced symptoms that suggested they had MS (this is commonly known as the clinically isolated syndrome [CIS]). Vitamin D is produced as a result of the skin being exposed to the sun and is converted by the body to 25-hydroxyvitamin D (25[OH]D). The amount of this metabolite in the blood was used to determine the patients’ vitamin D status in the study. The average blood serum level of 25(OH)D was a predictor of MS activity and disease progression: patients with higher 25(OH)D levels had less disease activity than those with lower levels of 25(OH)D. When the 25(OH)D levels were equal to or above the 50 nmol/L threshold, the risk of getting a diagnosis of clinically definite MS was reduced significantly. Magnetic resonance imaging (MRI) scans of patients with this higher level of 25(OH)D also showed less disease activity. In addition, higher 25(OH)D levels appeared to add to the treatment benefit of interferon beta-1b.

A second study, called BEYOND*, looked at how patients who had been diagnosed with relapsing-remitting MS (RRMS) responded to interferon beta-1b treatment. Patients in this study were from Western and Eastern Europe, North America and the Southern hemisphere. The 25(OH)D levels were the lowest in people living in Eastern Europe and highest in sunnier regions, such as Australia, Brazil and North America. This was expected as vitamin D is made in the skin following exposure to ultraviolet (UV) radiation from the sun. The investigators of the BEYOND study found that patients with higher levels of 25(OH)D had less signs of disease activity on their MRI scans. This benefit was seen regardless of what geographic region the people lived in.

How might vitamin D influence MS disease activity?
Gene studies have shown that vitamin D regulates genes that have roles in the immune system and that are associated with a decrease in MS disease activity. The effects of 25(OH)D on MS activity were enhanced further by interferon beta-1b. Some of the genes regulated by 25(OH)D are the targets of interferon beta-1b and this might, in part, explain this benefit between the drug and vitamin D. These findings mean that patients treated with interferon beta-1b could benefit from having their vitamin D levels monitored and managed with supplementation if vitamin deficiency is found. In a separate gene analysis genes predisposing people to vitamin D deficiency were identified. A risk score was derived from the cumulative number of risk genes a patient has, where a higher risk score indicates a greater chance of being 25(OH)D deficient.

How is the level of vitamin D important for people with MS treated with interferon beta-1b?
Evidence from animal models indicates that there is a link between vitamin D and treatment response to interferon beta-1b and there are also data available to indicate this link in patients with MS. In supplements and fortified foods, vitamin D is available in two forms, D2 (ergocalciferol) and D3 (cholecalciferol). The safety and effectiveness of adding vitamin D3 to interferon beta-1b treatment has been explored in a study of 66 patients with MS. Vitamin D3 add-on treatment to interferon beta-1b reduced the disease activity on MRI scans. In a study of 178 patients with clinically definite MS interferon-beta therapy was associated with greater production of vitamin D from sun exposure. This suggests that part of the therapeutic effect of the drug in people with MS may be mediated through vitamin D metabolism.

What do the scientific results mean for people living with MS?
It seems likely that there is an additive benefit from interferon beta-1b treatment and vitamin D in patients with MS. There are ongoing studies that are exploring the potential benefits of vitamin D supplementation in MS and, if the benefit is proven more conclusively, it may become standard to monitor vitamin D levels in patients with MS and provide vitamin D supplementation.

* STUDY NAMES
BENEFIT = BEtaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment
BEYOND = Betaferon/Betaseron Efficacy Yielding Outcomes of a New Dose in multiple sclerosis patients

Support: This project was supported by an educational grant from Bayer.

A lay summary on vitamin D deficiency in multiple sclerosis can be found HERE.