MULTIPLE SCLEROSIS: NEW IMMUNOMODULATORY STRATEGIES AND BIOMARKERS
Abstract
Introduction and purpose: Multiple Sclerosis (MS) disability accumulation is driven primarily by compartmentalized, subclinical neuroinflammation and diffuse neurodegeneration, termed smouldering MS. While traditional disease-modifying therapies (DMTs) control peripheral relapses and focal MRI activity, halting this progression remains a major challenge. Consequently, the therapeutic landscape is shifting toward novel central nervous system-targeting strategies to prevent Progression Independent of Relapse Activity (PIRA). The clinical utility of these interventions relies on highly sensitive fluid biomarkers, including serum neurofilament light (sNfL), serum glial fibrillary acidic protein (sGFAP), and kappa free light chains (kFLC), to track neuroaxonal injury, astrogliosis, and intrathecal immunoglobulin synthesis. This review evaluates the latest clinical evidence for next-generation immunomodulatory therapies, specifically autologous hematopoietic stem cell transplantation, Bruton’s tyrosine kinase inhibitors, and anti-CD20 monoclonal antibodies, alongside the diagnostic and prognostic roles of these emerging biomarkers. Materials and methods: The literature search was performed using PubMed, Scopus, Web of Science, and Google Scholar for articles published between 2020 and 2026. Keywords included: “multiple sclerosis”, “MS”, “serum neurofilament light”, “sNfL”, “serum glial fibrillary acidic protein”, “sGFAP”, “kappa free light chains”, “kFLC”, “autologous hematopoietic stem cell transplantation”, “aHSCT”, “brutons tyrosine kinase inhibitors”, “BTK inhibitors”, “tolebrutinib”, “anti-CD20”, “ofatumumab”, and “ublituximab”. Conclusion: Preventing PIRA requires a paradigm shift toward early, high-efficacy DMT utilization guided by multimodal biomarker profiling (sNfL, GFAP, kFLC). Although socioeconomic barriers often restrict early access, long-term pharmacoeconomic data demonstrate that timely intervention mitigates the substantial financial and societal burden of accumulated disability. Ultimately, combining these proactive clinical strategies with emerging therapeutic mechanisms, such as NLRP3 inflammasome inhibition or selective remyelination, offers the most promising avenue to alter the disease course and optimize healthcare resource utilization.