Multiple sclerosis (MS) is characterized as an autoimmune disease affecting the central nervous system. It is one of the most common neurological disorders in young adults. Over the past decades, increasing evidence suggested that hypovitaminosis D is a contributing factor to the risk of developing MS. From different risk factors contributing to the development of MS, vitamin D status is of particular interest since it is not only a modifiable risk factor but is also associated with MS disease activity. MS patients with lower serum vitamin D concentrations were shown to have higher disease activity. However, this finding does not demonstrate causality. In this regard, prospective vitamin D supplementation studies missed statistical significance in its primary endpoints but showed promising results in secondary outcome measures or post hoc analyses. An explanation for missed primary endpoints may be underpowered trials. Besides vitamin D supplementation as a potential add-on to long-term immunotherapeutic treatment, a recent laboratory study of our group pointed toward a beneficial effect of vitamin D to improve the efficacy of glucocorticoids in relapse therapy. In the following article, we will briefly review the effects of vitamin D on MS by outlining its effects on the immune and nervous system and by reviewing the association between vitamin D and MS risk as well as MS disease activity. We will also review the effects of vitamin D supplementation on MS risk and MS disease activity.

Background: In multiple sclerosis (MS), the frequency of hypogammaglobulinemia is unknown. We aimed to evaluate the frequency of reduced immunoglobulin (Ig) concentrations and its association with immunotherapy and disease course in two independent MS cohorts. Methods: In our retrospective cross-sectional study, MS patients and control patients with head or neck pain from Bern University Hospital (Bern, Switzerland) and Eginition University Hospital (Athens, Greece) were included. The lower limits of normal (LLN) for serum Ig concentration were IgG < 700 mg/dl, IgM < 40 mg/dl, and IgA < 70 mg/dl. Mann–Whitney U test, analysis of variance test, and multiple linear regression analysis were employed. Results: In total, 327 MS patients were retrospectively identified (Bern/Athens: n = 226/101). Serum IgG concentrations were frequently under LLN in both MS cohorts (Bern/Athens: 15.5%/14.9%), even when considering only untreated patients (Bern/Athens: 7.9%/8.6%). MS patients ( n = 327) were significantly more likely to have IgG concentrations below LLN and below 600 mg/dl in comparison with controls ( n = 58) ( p = 0.015 and 0.047, respectively). Between both patient groups, no significant differences were found in frequencies of IgA and IgM concentrations under LLN [ n (MS patients/controls): IgA 203/30, IgM 224/24]. Independently of age, secondary progressive MS patients had lower IgG concentrations than relapsing–remitting and primary progressive patients (both: p ⩽ 0.01). After adjusting for sex, age, and disease course, IgG concentrations were lower in patients treated with rituximab ( p = 0.001; n = 42/327), intravenous corticosteroids ( p < 0.001; n = 16/327), natalizumab ( p < 0.001; n = 48/327), and fingolimod ( p = 0.003; n = 6/327). Conclusion: Our study demonstrated high prevalence rates of reduced serum IgG concentrations in MS patients with and without disease-modifying treatments. The significance of lower IgG concentrations at the levels noted is unclear considering that infections or interference with antibody production generally occur when IgG levels are much lower, at or below 400 mg/dl. However, the information is useful to monitor IgG levels especially with anti-B-cell therapies and consider IgG substitution when levels drop below 400 mg/dl.

Dimethyl fumarate (DMF) was recently approved for treating patients with relapsing-remitting multiple sclerosis (RRMS) based on two phase III clinical trials demonstrating its efficacy. This prompts the need for demonstrating the clinical efficacy and safety of DMF in the real world. By retrospective analysis of medical records at two German MS centers, 644 MS patients treated with DMF were identified. All were included in a safety analysis, and a subgroup of patients with available efficacy data during previous MS therapies (n = 352) was further analyzed for annualized relapse rate and disability progression assessed by the EDSS. In the overall DMF population studied, the annualized relapse rate decreased from 0.52 at baseline to 0.35, and the annualized disability progression from 0.15 to 0.10. Patients who were switched from interferons or glatiramer acetate to DMF revealed a greater benefit, whereas patients pretreated with more potent immunotherapies did not respond that well. Interestingly, patients with a lymphocyte count ≥2000/µl after 0.52 years (mean, SD 0.2) of DMF treatment did not benefit compared to those with lower lymphocyte counts. In total, 22.2 % of the patients withdrew from DMF due to side effects, with gastrointestinal discomfort (12.7 %) and lymphopenia (5.3 %) as most frequently reported reasons. Our study corroborates that DMF is an overall safe and effective drug that reduces relapse rate as well as disability progression in MS patients. Further prospective studies are warranted to establish the additional parameters predicting DMF response, especially in patients switching from other first-line immunotherapies.