Tobias Moser

Objective: To describe long‐term outcomes after anti‐CD20 discontinuation in selected patients with secondary progressive multiple sclerosis (SPMS) who remained without subsequent disease‐modifying therapy (DMT). Methods: We retrospectively analyzed data from four centers in Austria and Switzerland. Inclusion criteria were SPMS, ≥ 2 anti‐CD20 cycles, discontinuation without subsequent DMT, and ≥ 36 months follow‐up. The primary endpoint was time to first confirmed Expanded Disability Status Scale (EDSS) worsening, defined as a ≥ 0.5‐point increase after discontinuation documented at a subsequent routine visit. Secondary endpoints were relapses, MRI activity, and severe infections. No continuation cohort was available. Results: Fifty‐five patients were included (61% female). Mean age at anti‐CD20 start was 53.5 ± 6.6 years, disease duration 19.3 ± 10.1 years, treatment duration 32.8 ± 16.1 months, and post‐discontinuation follow‐up 55.1 ± 14.1 months. Mean EDSS increased from 5.9 ± 1.3 before anti CD20, to 6.3 ± 1.3 at discontinuation and 6.9 ± 1.2 at last follow‐up. Confirmed EDSS worsening occurred in 31 patients (56%). Hazard analysis suggested an exploratory late increase between 48 and 60 months ( p = 0.043) based on small numbers at risk. Relapses occurred in 6 patients (10.9%), MRI activity in 4/35 (11%), and severe infections in 17 (31%). Conclusions: In this selected SPMS cohort, focal inflammatory activity was uncommon, whereas confirmed EDSS worsening accumulated over long‐term follow‐up. Because inclusion required ≥ 36 months untreated follow‐up, early disease activity may have been underestimated, and apparent stability may have been overestimated. Findings are descriptive and hypothesis‐generating and do not establish safety or optimal timing of anti‐CD20 discontinuation.

Propionic acid (PA), a microbial-derived short-chain fatty acid, contributes to intestinal barrier integrity, systemic immune regulation, and neuronal function. Individuals with multiple sclerosis show reduced PA levels, and open-label data have suggested beneficial immunomodulatory and clinical effects of supplementation. The Multiple sclerosis And DisAbility Improvement (MADAI) trial was a randomized, double-blind, placebo-controlled, single-centre, phase 2b study designed to evaluate the efficacy and safety of PA as an add-on therapy in adults with clinically stable multiple sclerosis. Between April 5 and 29 May 2024, 101 adults (64% women; mean age 45 years) were randomly assigned in a 2:1 ratio to receive PA 500 mg twice daily or matching placebo for 90 days. The primary outcome was the change in serum neurofilament light chain (sNfL) concentration, a biomarker of neuroaxonal damage, adjusted for age, body mass index, creatinine, and baseline sNfL. Secondary outcomes included physical and cognitive performance measures and patient-reported outcomes, including fatigue and quality of life scores. sNfL levels were significantly reduced in the PA group {−17.9%; from 9.77 pg/ml [95% confidence interval (CI) 9.00 to 10.60] to 8.02 pg/ml (95% CI 7.36 to 8.73); mean difference 1.75 pg/ml (95% CI 0.9 to 2.6); P = 0.000025}, while no significant change was observed in the placebo group. The adjusted mean difference in sNfL levels between the PA and placebo groups at follow-up was 0.91 pg/ml (95% CI 0.02 to 1.79; P = 0.045). Reductions in sNfL were also observed among participants in the PA arm receiving moderate-to-high efficacy disease-modifying therapies (n = 41; P = 0.0001), including those on anti-CD20 treatment (n = 27; P = 0.0005). There was a trend towards improvement in motor fatigue in the PA group. No serious adverse events related to the study medication occurred. PA supplementation was well tolerated and associated with significant reductions in sNfL, suggesting attenuation of neuroaxonal injury in multiple sclerosis. These findings support further evaluation of PA as an add-on treatment in larger, long-term studies.

Over the past two decades, anti-CD20 monoclonal antibodies have become a cornerstone in the management of B cell malignancies and autoimmune diseases, including multiple sclerosis (MS). Although their ability to induce profound depletion of peripheral B cells is well established, the broader spectrum of their immunomodulatory actions remains incompletely understood. This gap is clinically relevant, as treatment responses in MS do not consistently correlate with peripheral B cell counts. Moreover, tissue-resident B cells, particularly those within the central nervous system (CNS) and secondary lymphoid organs, as well as long-lived plasma cells, are largely unaffected by anti-CD20 therapy. These observations underscore the need to elucidate additional mechanisms contributing to therapeutic efficacy, including effects in antibody-mediated disorders such as neuromyelitis optica spectrum disorder (NMOSD). In this review, we focus on preclinical and clinical evidence concerning the effects of anti-CD20 therapies on soluble immunological mediators—cytokines, chemokines, and adhesion molecules—across MS. Emerging data suggest anti-CD20 treatments may restore the balance between pro-inflammatory and regulatory pathways, indirectly modulating other immune cell populations. However, available studies are constrained by small sample sizes, heterogeneous methods, and variable patient populations. Future systematic investigations are needed to clarify mechanisms of action, guide rational combination therapies, improve understanding of treatment response and side effects, and deepen insights into the underlying disease itself.

Given the financial constraints in public healthcare, we investigated the monthly out-of-pocket expenses for non-pharmacological treatments among individuals with multiple sclerosis (MS), a chronic neurological disorder that primarily affects individuals of working age. This cross-sectional study employed an online questionnaire to evaluate the expenses and utilization of non-pharmacological treatments, as well as the weekly working hours among 104 individuals with relapsing-remitting MS (RRMS, 79%), secondary progressive MS (SPMS, 12%), and primary progressive MS (PPMS, 10%). Non-pharmacological treatments were used by 82% of participants (vitamin D (43%), physiotherapy (31%), massage (21%), magnesium (19%)). The average monthly out-of-pocket expenses were 136 EUR (SD ± 218) and significantly higher among individuals with PPMS (337 EUR SD ± 354) compared to RRMS (110 EUR SD ± 195; p = 0.01). The average weekly working hours were 26 and significantly lower among individuals with PPMS (11 h/week, SD ± 16; p = 0.008) and SPMS (13 h/week, SD ± 16; p = 0.001) compared to the RRMS cohort (30 h/week, SD ± 15). Working hours were not related to individual monthly costs. This study reveals substantial expenses incurred by individuals with MS in Austria, particularly those with PPMS, highlighting the willingness to actively participate in their disease management. Physicians should be aware of the financial resources and inform about available evidence on non-pharmacological treatment approaches.

We aimed to determine whether transient global amnesia (TGA) is associated with alterations in central nervous system (CNS) injury biomarkers—serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP). In a prospective cohort of TGA patients, blood samples were obtained within 24–48 h of TGA onset (t0) and 6 weeks thereafter (t1). We assessed sNfL and sGFAP levels using the highly sensitive single-molecule array assay and calculated Z-scores adjusted for age, gender, and body mass index (BMI). Demographics, electroencephalography (EEG), and cerebral magnetic resonance imaging (cMRI) findings were also collected. A total of 20 patients were included (median age: 66 years, 70% women). No significant changes in sNfL or sGFAP levels associated with TGA at t0 and t1 were observed. Median sNfL Z-scores were 0.45 (interquartile range [IQR] −0.09, 1.19) at t0 and 0.60 (IQR −0.61, 1.19) at t1. Median sGFAP Z-scores were 0.27 (IQR −0.45, 0.76) at t0 and 0.44 (IQR −0.27, 0.75) at t1. Similarly, in the subgroup of patients with diffusion-weighted imaging (DWI)-positive hippocampal lesions (n = 5/20[25%]), no elevations in blood biomarkers were detected. Our pilot study on neurological blood biomarkers supports the benign nature of TGA, indicating that no CNS tissue damage occurs.

Anti-CD20 therapies are highly effective treatment options for patients with multiple sclerosis (MS), an inflammatory disorder of the CNS commonly affecting women of childbearing age. Anti-CD20 therapies are however unlicensed for use in pregnancy. Belonging to the IgG1 family, anti-CD20 monoclonal antibodies are likely to cross the placenta, especially after the 20th week of gestation. Our objective was to analyze the impact of ofatumumab (OFA), a subcutaneous anti-CD20 monoclonal antibody, during pregnancy. We present the case of a woman with MS who accidentally administered OFA every 4 weeks until delivery. In addition to detailing the clinical and laboratory outcomes of both mother and child, we provide a summary of the available evidence regarding anti-CD20 treatment during pregnancy and breastfeeding. Our patient gave birth to a healthy girl between estimated gestational weeks 32–35. Notably, at 3 months postpartum and 4 months after the last OFA administration, the mother remained fully B-cell depleted while the B-cell counts of the child were within the normal range. Further data are necessary to confirm that OFA treatment during pregnancy does not affect neonatal B cells.

Background: Cladribine (CLAD), an immune reconstitution therapy for active multiple sclerosis (MS), can reduce intrathecal antibody production. Objectives: In this study, we investigated the long-term impact of oral CLAD on protective antibody levels, essential for preventing infections and immune defense. Design: Observational long-term study including a cohort of 15 CLAD-treated MS patients. Methods: We longitudinally studied the humoral immunity to seven common pathogens (measles, mumps, varicella-zoster virus, diphtheria and tetanus toxin, rubella, hepatitis B virus (HBV)) and absolute immunoglobulin G (IgG) levels prior to CLAD treatment (baseline, BL; 12/2017–03/2020) and after an average of 73 months (long-term) follow-up to explore the impact on pre-existing IgG. At long-term, we assessed IgG response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to evaluate potential inhibitory effects on the formation of new immunity. Results: We found no CLAD associated loss of humoral immunity over up to 7 years. Pathogen-specific IgG antibodies were present in 60%–100% and 67%–100% of patients at BL and long-term, respectively. We found no decline in absolute IgG levels 73 months after starting CLAD treatment. Patients who received subsequent anti-CD20 treatment had significantly lower SARS-CoV-2 antibody levels ( p = 0.011) compared to the rest of the cohort, which developed adequate anti-SARS-CoV-2 IgG. One patient had a clinically silent tick-borne encephalitis (TBE) infection mounting appropriate IgG and IgM. No severe COVID-19 cases occurred, and no new safety concerns were identified. Conclusion: These long-term data suggest that CLAD treatment does not impact preexisting humoral immunity or antibody production toward novel antigens. Our results support the positive long-term safety profile of the drug.

Background/Objective: Observational real‐world study to analyze the clinical effects of alemtuzumab (ALEM) and subsequent disease‐modifying therapy (DMT) usage in multiple sclerosis (MS).Methods: Data retrieved from the Austrian MS treatment registry (AMSTR) included baseline (BL) characteristics (at ALEM start), annualized relapse rate (ARR), 6‐month confirmed progression independent of relapse activity (PIRA; ≥ 0.5‐point Expanded Disability Status Scale (EDSS) score increase), 6‐month confirmed disability improvement (CDI; ≥ 0.5‐point EDSS decrease), and safety outcomes until initiation of a subsequent DMT. The EDSS was re‐baselined at 30 days from ALEM start (BL EDSS).Results: Eighty‐seven ALEM‐treated patients (median age: 32 years, 72% female, 14% treatment‐naïve) were followed for a median of 55 (interquartile range 31–68) months. We found significant reductions in the ARR from 1.16 before ALEM to 0.15 throughout Years 1–9 (p < 0.001). Subsequent DMTs were initiated in 19 patients (22%, 74% anti‐CD20 monoclonal antibodies). At Year 5 (n = 53), more patients achieved CDI (58%, 95% confidence interval (CI) 45%–71%) than had experienced PIRA (14%, CI 7.5%–24%), and 58% remained relapse‐free. Shorter MS duration (p < 0.001, hazard ratio (HR) 0.86 (CI 0.80–0.93)) and no previous high‐efficacy treatment (p < 0.001, HR 5.16 (CI 2.66–10.0)) were the best predictors of CDI, while PIRA was associated with a higher number of previous DMTs (p = 0.04, HR 3.06, CI 1.05–8.89). We found no new safety signals.Interpretation: ALEM had long‐lasting beneficial effects on the ARR and disability improvement, especially when initiated early in the course of the disease. Only a subset of patients received subsequent DMTs.

Facial nerve palsy is most commonly idiopathic, but it can also result from infections, inflammatory and cerebrovascular disorders, tumors, and trauma. We report the case of a 68-year-old patient who developed iatrogenic facial nerve palsy subsequent to dermatological cryosurgery on the right cheek. Remarkably, a full recovery occurred within 8 weeks. Drawing upon the promising outcome of this case and the existing literature on neuropathies linked with cold application in sports injuries, we propose neurapraxia as the probable pathomechanism underlying cryotherapy-induced nerve damage.