OBJECTIVE: The impact of SARS-CoV-2 infection on brain and spinal cord pathology in patients with multiple sclerosis (pwMS) remains unclear. We aimed to describe changes in brain lesion activity and brain and spinal cord volumes following SARS-CoV-2 infection. METHODS: We included 177 pwMS (570 MRI scans) diagnosed with and tested positive for SARS-CoV-2 infection between August 2020 and May 2021. All patients were free of clinical disease activity, disease-modifying therapy changes, and corticosteroids during the study. MRI scans were performed using a standardized protocol on a 3-Tesla scanner. We analyzed the effect of SARS-CoV-2 on brain lesion load accrual and brain and spinal cord volume measures using adjusted mixed-effect models. RESULTS: During SARS-CoV-2 infection, patients had a median disease duration of 14.2 years, a median age of 44.9 years, and a median Expanded Disability Status Scale of 2.0. SARS-CoV-2 infection did not lead to any changes in the number or volume of T1 or T2 lesions in the brain. However, SARS-CoV-2 was associated with an increased whole brain (B = -0.17; SE = 0.08; p = 0.028), grey matter (B = -0.25; SE = 0.12; p = 0.040), and cortical grey matter volume loss (B = -0.32; SE = 0.13; p = 0.014). Greater ventricular enlargement following SARS-CoV-2 infection was evident only in individuals over the age of 40 (interaction of age vs. ventricular enlargement: B = 0.17; SE = 0.05; p = 0.0003). Only patients with more severe SARS-CoV-2 infection showed a reduction in mean upper cervical cord area (MUCCA) (B = 1.14; SE = 0.52; p = 0.030). INTERPRETATION: SARS-CoV-2 infection in clinically stable pwMS was linked to increased neuronal tissue loss.

• Keywords
• COVID‐19, MRI, SARS‐CoV‐2, brain atrophy, brain lesion, multiple sclerosis,
• MeSH
• COVID-19 * complications   pathology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Spinal Cord * pathology   diagnostic imaging   MeSH
• Brain * pathology   diagnostic imaging   MeSH
• Multiple Sclerosis * pathology   diagnostic imaging   MeSH
• SARS-CoV-2 MeSH
• Gray Matter pathology   diagnostic imaging   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS). OBJECTIVES: Provide experience with cladribine therapy in a real-world setting. METHODS: This is a registry-based retrospective observational cohort study. First, using data from the Czech nationwide registry ReMuS, we analysed patients who initiated cladribine from September 1, 2018 to December 31, 2021. Second, we analysed a subgroup of patients who initiated cladribine between September 1, 2018 to June 30, 2020, thus possessing a follow-up period of at least 2 years. We evaluated demographic and MS characteristics including disease-modifying therapies (DMTs) before and after cladribine administration, relapses, Expanded Disability Status Scale (EDSS), and adherence. RESULTS: In total, 617 patients (335 with follow-up of at least 2 years) started cladribine therapy in the study period (mean age 37.0, mean disease duration 8.4 years, 74.1% females). In most cases, cladribine was administered as a second-line drug, a total of 80.7% had been escalated from a platform DMT. During 2 years before cladribine initiation, the average annualised relapse rate (ARR) was .67. Following cladribine initiation, the ARR decreased to .28 in the first year and .22 in the second year. Overall, across the entire two-year treatment period, 69.0% of patients were relapse-free and the average ARR was .25. As for EDSS development, the median baseline EDSS was 2.5 and remained stable even after 24 months. The adherence to treatment ranged of around 90%. CONCLUSION: This nationwide study confirms the efficacy of cladribine in real-world settings, especially in patients who are not treatment-naïve. In addition, the study shows an exceptionally high adherence rate, a finding that underscores the invaluable role of cladribine, but also the value of registry-based studies in capturing real-world clinical practice.

• Keywords
• Cladribine, adherence, annualised relapse rate, expanded disability status scale, high-efficacy disease-modifying therapy, multiple sclerosis,
• Publication type
• Journal Article MeSH

BACKGROUND: The Big Multiple Sclerosis Data (BMSD) network ( https://bigmsdata.org ) was initiated in 2014 and includes the national multiple sclerosis (MS) registries of the Czech Republic, Denmark, France, Italy, and Sweden as well as the international MSBase registry. BMSD has addressed the ethical, legal, technical, and governance-related challenges for data sharing and so far, published three scientific papers on pooled datasets as proof of concept for its collaborative design. DATA COLLECTION: Although BMSD registries operate independently on different platforms, similarities in variables, definitions and data structure allow joint analysis of data. Certain coordinated modifications in how the registries collect adverse event data have been implemented after BMSD consensus decisions, showing the ability to develop together. DATA MANAGEMENT: Scientific projects can be proposed by external sponsors via the coordinating centre and each registry decides independently on participation, respecting its governance structure. Research datasets are established in a project-to-project fashion and a project-specific data model is developed, based on a unifying core data model. To overcome challenges in data sharing, BMSD has developed procedures for federated data analysis. FUTURE PERSPECTIVES: Presently, BMSD is seeking a qualification opinion from the European Medicines Agency (EMA) to conduct post-authorization safety studies (PASS) and aims to pursue a qualification opinion also for post-authorization effectiveness studies (PAES). BMSD aspires to promote the advancement of real-world evidence research in the MS field.

• Keywords
• Multiple sclerosis, Patient data network, Patient registries, Real-world evidence,
• MeSH
• Big Data MeSH
• Humans MeSH
• International Cooperation MeSH
• Registries * MeSH
• Multiple Sclerosis * epidemiology   therapy   MeSH
• Information Dissemination MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH