Background: Reporting of sex-specific analyses in multiple sclerosis (MS) is sparse. Disability accrual results from relapses (relapse-associated worsening) and independent thereof (progression independent of relapses). Objectives: A population of MS patients during relapse treated per standard of care was analyzed for sex differences and short-term relapse outcome (3–6 months) as measured by Expanded Disability Status Scale (EDSS) change. Design: Single-center retrospective study. Methods: We analyzed 134 MS relapses between March 2016 and August 2020. All events required relapse treatment (steroids and/or plasma exchange). Demographic, disease, and paraclinical characteristics [cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI)] were displayed separated by sex. Multivariable linear regression was run to identify factors associated with short-term EDSS change. Results: Mean age at relapse was 38.4 years (95% confidence interval: 36.3–40.4) with a proportion of 71.6% women in our cohort. Smoking was more than twice as prevalent in men (65.8%) than women (32.3%). In- and after-relapse EDSSs were higher in men [men: 3.3 (2.8–3.9), women: 2.7 (2.4–3.0); men: 3.0 (1.3–3.6); women: 1.8 (1.5–2.1)] despite similar relapse intervention. Paraclinical parameters revealed no sex differences. Our primary model identified female sex, younger age, and higher EDSS at relapse to be associated with EDSS improvement. A higher immunoglobulin G (IgG) quotient (CSF/serum) was associated with poorer short-term outcome [mean days between first relapse treatment and last EDSS assessment 130.2 (79.3–181.0)]. Conclusion: Sex and gender differences are important in outcome analyses of MS relapses. Effective treatment regimens need to respect putative markers for a worse outcome to modify long-term prognosis such as clinical and demographic variables, complemented by intrathecal IgG synthesis. Prospective trials should be designed to address these differences and confirm our results.

A large number of disease-modifying immunotherapies are available for the treatment of people with multiple sclerosis. Many disease-modifying immunotherapies show scarce or no safety data in pregnancy and breastfeeding and are labeled as being contraindicated during these periods in the Swiss summary of product characteristics. Some disease-modifying immunotherapies also have restrictions for male patients. Hence, family planning should always be considered in treatment decisions. If clinically necessary, the continuation of immunotherapy during pregnancy can be considered for some substances. In these situations, the “Good Off-Label Use Practice”, careful consideration of the benefit–risk profile, and interprofessional cooperation between the treating neurologist, obstetrician–gynecologist, and pharmacist/pharmacologist, ideally with the involvement of experienced centers, is necessary. Here, we present an update on disease-modifying immunotherapies in multiple sclerosis with a focus on family planning, pregnancy, and breastfeeding and provide consensus recommendations of the Medico-Scientific Advisory Board of the Swiss Multiple Sclerosis Society, the Swiss Neurological Society, and the Swiss Society for Gynecology and Obstetrics (represented by the Academy of Fetomaternal Medicine). These unified national recommendations are necessary, as guidelines from other countries differ and because of separate approval/reimbursement situations in Switzerland.

Introduction: Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 (cluster of differentiation) monoclonal antibodies (mAbs) such as ocrelizumab (OCR) and ofatumumab (OFA) show a reduction mainly of B-lymphocytes, but also other lymphocyte subsets can be affected by these treatments. There is limited data on differences between lymphocyte subset counts of pwMS after treatment initiation with OCR or OFA. Objective: To compare lymphocyte subset counts after treatment initiation in pwMS treated with OCR and OFA. Methods: We analyzed 22 pwMS initiated on OFA and 56 sex-, age- and MS course matched pwMS initiated on OCR from 2 prospectively collected observational MS databases (Bern [n: OFA 14, OCR 44] and Vienna [n: OFA 8, OCR 12]) statistically comparing lymphocyte subset counts (Mann Whitney Test). Results: We found that pwMS treated with OCR showed a stronger reduction of CD20 B-lymphocytes ( P = .001), and a trend towards lower counts of CD8⁺ T cells ( P = .056) compared to pwMS treated with OFA, whereas reduction of total lymphocyte, CD4⁺ lymphocyte and NK cell count was equally distributed between both treatments. Conclusion: Different effects on lymphocyte subpopulations appear to be present in pwMS after treatment initiation with different anti-CD20 mAbs. Further studies are needed to determine potential effects on anti-CD20 treatment efficacy as well as treatment associated risks such as failed vaccinations and infections.

Objective: Anti-CD20-treated patients are at risk of a reduced humoral immune response during the SARS-CoV-2 pandemic. Our aim was to compare the antibody response after two vaccinations with the mRNA vaccines BNT162b2 or mRNA-1273 in patients with multiple sclerosis. Methods: Data from the University Hospital of Bern and Cantonal Hospital of Lucerne were retrospectively collected from medical records and then analyzed. Anti-spike IgG serum titers were collected from both centers and were considered to be protective from a value of ≥100 AU/mL. Continuous variables were given as the mean and 95% confidence interval (95% CI); categorical variables were given as frequencies. A Mann–Whitney test and Fisher’s exact test as well as a multivariable linear regression analysis with anti-spike IgG (AU/mL) as the dependent variable were run using SPSS Statistic 25 (IBM Corp., Amonk, NY, USA). Results: A total of 74 patients were included; 41/74 (63.51%) were female patients and the mean age was 46.6 years (95% CI 43.4–49.9). Of these patients, 36/74 were vaccinated with BNT162b2 and 38/74 with mRNA-1273, following the national vaccination recommendation. In both vaccine groups, protective anti-spike IgG titers (≥100 AU/mL) were infrequently achieved (5/74: mRNA-1273 3/38; BNT162b2 2/36). Conclusions: In addition to a low rate of protective anti-spike IgG titers in both vaccine groups, we identified a drop in anti-spike IgG serum titers over time. This observation bears therapeutic consequences, as initial positive titers should be checked in case of an infection with the SARS-CoV-2 virus to identify patients who would benefit from an intravenous anti-spike IgG treatment against acute COVID-19.