Understanding the 'Durable Effect' Concept of B-cell Modulating Therapies

B cell targeted therapies have become a key element in the treatment of multiple sclerosis due to their effectiveness in rapid and long-lasting depletion of B cells in peripheral blood (PB), significantly reducing relapse rates and disability progression. The monoclonal antibodies OFA, OCR, UBX, and RTX target the B cell surface protein CD20, however it is unclear how B cell depletion and subsequent repopulation allows for immune system reconstitution and how other immune cell populations are affected by these therapies. Furthermore, the relevance of immune cell changes - beyond B cell depletion - for clinical disease stability remains insufficiently understood.

By collecting comprehensive and structured prospective clinical data alongside immunological analyses, this study aims for a better understanding of immunological changes in RRMS patients receiving anti-CD20 therapies and the implications of those alterations in immune cell profiles on the clinical disease course. REBELLION-MS plans for two patient cohorts: cohort 1 (C1; basic cohort) and cohort 2 (C2; in-depth cohort). Participants in C1 will be seen every 6 months up until month 24, then every 12 months. The following parameters will be collected: demographic data, disease characteristics incl. Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) data, serum samples, and Peripheral Blood Mononuclear Cells (PBMCs). Furthermore, Short Form-36 (SF-36) and Fatigue Scale for Motor and Cognitive Functions (FSMC) are documented. Participants of C2 will receive additional evaluations: clinical evaluation incl. EDSS and sampling of serum and PBMCs at months 1 and 3, Multiple sclerosis functional composite (MFSC) every 6 months, and optical coherence tomography (OCT) as well as neuropsychological assessment (NPT) every 12 months. Serum samples and PBMCs will be analyzed by mFC, bulk-Seq, TCR/BCR-Seq, and proteomics, among other methods.

• Change from baseline in Expanded Disability Status Scale (EDSS) Score [Срок оценки: Baseline up to 48 months]
• Change from baseline in Short Form Health Survey (SF-36) [Срок оценки: Baseline up to 48 months]
• Change from baseline on Magnetic Resonance Imaging (MRI) [Срок оценки: Baseline up to 48 months]
• Change from baseline in Retinal Nerve Fiber Layer thickness (RNFL) [Срок оценки: Baseline up to 48 months]
• Change from baseline in visual acuity (HCV and LCV) [Срок оценки: Baseline up to 48 months]
• Change from baseline in Fatigue Scale for Motor and Cognitive Functions (FSMC) [Срок оценки: Baseline up to 48 months]
• Change from baseline in Multiple Sclerosis Functional Composite (MSFC) Score [Срок оценки: Baseline up to 48 months]
• Change from baseline in Symbol Digit Modalities Test (SDMT) [Срок оценки: Baseline up to 48 months]
• Change from baseline in Verbal Memory Learning Test (VMLT) [Срок оценки: Baseline up to 48 months]
• Change from baseline in Brief Visuospatial Memory Test (BVMT) [Срок оценки: Baseline up to 48 months]
• Change from baseline in Montreal Cognitive Assessment (MoCA) [Срок оценки: Baseline up to 48 months]
• Change from baseline in BDI-FS/BDI II [Срок оценки: Baseline up to 48 months]