Background: Ocrelizumab (OCR) is a humanized monoclonal antibody directed against CD -20 positive lymphocytes, mainly B-lymphocytes. OCR is approved for treatment of primary progressive (PPMS) and relapsing multiple sclerosis (RMS). This study aims to provide real -world safety and efficacy data of people with RMS treated with OCR in two Swiss Multiple Sclerosis (MS) centers. Methods: We have conducted a retrospective data analysis using the patient cohorts from the Cantonal Hospital Aarau and Bern University Hospital (RMS: n = 235). Statistical analyses were performed with Mann -Whitney UTest, Chi-squared test and Spearman-Rho-Correlation. Adjustment for multiple testing was performed by Bonferroni procedure. Results: After initiation of OCR, there was a decrease in disease activity in RMS patients. In our study, 152/190 (80.0 %) RMS patients fulfilled the criteria for NEDA-3 12 months and 88/104 (84.6 %) showed NEDA-3 24 months after OCR initiation. The most frequent adverse events (AEs) in our study were infections, taking place in 78/235 (33.2 %) RMS patients. COVID-19 was the most common infection, followed by urinary infections and other respiratory infections and infectious adverse events occurred significantly more frequent in patients with reduced IgG serum concentration. Conclusions: Our real -world study showed OCR being associated with low rates of any type of MS disease activity as indicated by NEDA-3. The adverse event profile is comparable to the known events especially infections and an association between infections and reduced IgG serum concentration was found.

Objective: Neutropenia is a rare complication of anti-CD20 treatment, such as Ocrelizumab (OCR) in Multiple Sclerosis (MS). Using FDAs Adverse Event Reporting System (FAERS), a post-marketing, open access pharmacovigilance database, we aimed to identify risk factors of neutropenia in OCR-treated patients. Methods: : Data were retrieved from FAERS identifying OCR-treated patients with and without neutropenia. Only data with OCR as the single suspected product were considered. Multivariable logistic regression (MLR) analysis was run to study if MS disease course, age, sex and bodyweight were associated with the risk of neutropenia. Results: Of 15,313 initial hits, 3177 complete datasets were included in the analysis. MLR demonstrated that MS disease course was not associated, whereas sex (female sex (reference male sex) 0.356, 95%CI 0.145-0.875, p = 0.0124), age (years, 0.909, 95%CI 0.875-0.944, p = 7.4105 x 10(-7)) and bodyweight (kilogram, 0.961, 95%CI 0.935-0.988, p = 0.005) were factors associated with OCR-related neutropenia (Nagelkerkes R-2 =0.17, n = 3177). No deaths were reported for identified neutropenia cases. Conclusion: Using FAERS, we identified male sex, younger age and lower bodyweight as factors associated with OCR-related neutropenia. With the limitations inherent to this open data source, our data need prospective validation, but elucidate potential factors for a personalized side effect profiling.

Objective: Fatigue is one of the most disabling and difficult to treat symptoms of autoimmune diseases and frequently presents in people with multiple sclerosis (PwMS). Hypogammaglobulinemia for immunoglobulin G (IgG) affects approximately 8-25% of PwMS. We performed a retrospective analysis to investigate the association of MS-fatigue and IgG hypogammaglobulinemia. Methods: PwMS, treated at Eginition University Hospital Athens or at the University Hospital Bern, were included (n = 134 patients (Bern n = 99; Athens n = 35)). Mann Whitney U-test (MWT), ANOVA test, Chi2 test and multivariable linear regression models were run. Results: 97/134 (72.4%) PwMS reported fatigue. In the multivariable linear regression analysis, IgG serum concentration (-1.6, 95%CI -2.7 --0.5, p = 0.006), daytime sleepiness (0.8, 95%CI 0.2-1.4, p = 0.009), and a depressive mood (1.1, 95%CI 0.8-1.4, p < 0.001) were significantly associated with fatigue. The impact of IgG serum concentration (-2.9 95%CI-4.7 --1.1,p = 0.002) remained significant also in the subcohort of PwMS without depressive symptoms or daytime sleepiness. Conclusions: We found an association between IgG hypogammaglobulinemia and fatigue in PwMS (Level of Evidence IV), which might be translated to other autoimmune diseases. It bears a potential therapeutic conse-quence considering IgG supplementation strategies, if our finding can be validated prospectively.

Background: Anti-CD20 therapies are an emerging treatment strategy in multiple sclerosis (MS). Objective: Retrospective analysis of efficacy and safety in an MS cohort treated with rituximab (RTX) with identification of potential treatment response predictors. Methods: This retrospective study describes a monocentric cohort of 30 MS patients treated with RTX in a routine clinical setting. Patient characteristics, disease course, clinical and magnetic resonance imaging (MRI) treatment response markers, and laboratory assessments were analyzed. Logistic regression analysis corrected for demographic characteristics was used to identify treatment response predictors. Results: The RTX-treated cohort (mean age at RTX initiation 48 years (SD 14)) comprised patients with relapsing-remitting MS (n = 9), primary progressive MS (n = 11), and secondary progressive MS (n = 10). Two-thirds of patients had at least one MS medication prior to RTX; 27.6% of patients improved on the Expanded Disability Status Scale during RTX, whereas 72.4% of patients were stable or worsened. Based on this classification, we identified the presence of gadolinium enhancement in MRI before RTX as a predictor of response (odds ratio (OR) 12.2, confidence interval (CI) 1.02–144.55). After receiver operating characteristic curve definition of immunoglobulin (Ig) class cutoffs and creation of a sum score, the latter also predicted RTX response (OR 5.15, CI 1.21–21.88). Infectious complications were seen in three patients under RTX treatment. Conclusion: With the limitation of the retrospective approach and small sample size, this study confirms gadolinium enhancement before treatment initiation as a predictor of anti-CD20 response in MS. Lower Ig levels were associated with RTX response; however, these will have to be further investigated for a potential role for infectious complications.