Demyelinating Autoimmune Diseases, CNS

In this protocol, a combination of MRI, blood, and cerebrospinal fluid (CSF) analysis will be used to understand the natural history, underlying immunologic mechanisms, and clinical implications of central nervous system (CNS) lesions, in particular lesions in the cerebral cortex, in multiple sclerosis (MS) and other inflammatory and autoimmune disorders affecting the CNS. Patients with these disorders, as well as healthy controls, will undergo baseline clinical evaluation and testing, bloodwork, and MRI, with follow up clinical evaluation, bloodwork, and MRI at years 1, 3, and 6. Additional MRIs may be performed in patients with possible new lesion formation or to compare MRI techniques. Lumbar puncture will be performed on participants who are not currently being treated with disease modifying therapies and who are willing to undergo the procedure.

Title: Study of Inectolizumab Combined With Steroid Hormone Adjustment Strategies in Treatment-naive Patients With Neuromyelitis Optica Spectrum Disease Objective:This study aims to evaluate the steroid-sparing effect and safety of inebilizumab in treatment-naïve AQP4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) patients, while assessing its impact on EDSS score improvement during acute-phase treatment. The study will further explore treatment-related biomarkers, including dynamic changes in: immunoglobulin levels, lymphocyte subset profiles, serum AQP4-IgG titers, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) levels. Study Design:This is a single-center, randomized, open-label, prospective clinical study planning to enroll 25 treatment-naïve, anti-aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD) patients.

Rationale: Ocrelizumab is widely and effectively used to treat relapsing multiple sclerosis (RMS). Phase II studies and data from large patient cohorts indicate that rituximab, another anti-CD20 monoclonal antibody, is probably equally effective and safe as ocrelizumab in the treatment of RMS. An advantage of rituximab is a considerably lower price. Therefore we will start a study aimed at demonstrating non-inferiority of rituximab compared to ocrelizumab in RMS. If non-inferiority of rituximab can be shown, important reductions in the cost of treatment of RMS will be possible, without loss of efficacy. Objective: Evaluating the efficacy and safety of ritixumab compared to ocrelizumab in the treatmens of RMS. Study design: Randomized double blind multi-centre non-inferiority study of rituximab compared to ocrelizumab in 200 patients with RMS. The trial duration will be 30 months Study population: The study population consists of 200 adult RMS patiens with an indication to start anti-CD20 monoclonal antibody treatment. Intervention: Patients will be randomized 1:1 into the standard group (ocrelizumab treatment) or the experimental group (rituximab treatment). Main study parameters: To conclude non-inferiority of rituximab there will be one primary endpoint: the proportion of patients free of inflammatory disease activity (defined as: new or enlarged T2 lesions) between week 24 (M6) and week 96 (M24) of treatment in each arm. Secondary trial endpoints are presence and number of clinical relapses,T2 and contrast enhancing lesion volumes, brain volume and brain volume changes, disease progression (defined as clinically relevant change on any of the measures: EDSS, T25FW, 9HPT, SDMT), biochemical parameters such as lipidomics and neurofilament light (NfL), immunological parameters, safety as measured by the number of (serious) adverse events ((S)AE), quality of life (EQ-5D-L) and treatment satisfaction (TSQM) and patient reported measures of MS impact (MSIS-29) and well-being (questionnaire on physical complaints) Nature and extent of the burden and risk: Patients included in this study will be treated and monitored by MRI, clinical tests and laboratory tests according to existing protocols and will not be exposed to extra or unknown risks. They will have extra annual questionnaires and larger blood samples at some time points. There is extensive experience with both rituximab and ocrelizumab as efficacious and safe treatments of RMS.