Therapeutic Advances and Biomarkers in Multiple Sclerosis

Introduction: High-efficacy Disease-Modifying Therapies (DMTs) have transformed relapse control in multiple sclerosis, yet Progression Independent of Relapse Activity (PIRA) per-sists. This review aims to synthesize contemporary therapeutic advances and clarify how emerging biomarkers assess treatment efficacy. Methods: This narrative review includes randomized trials, prospective cohorts, open-label exten-sions, and major regulatory/congress communications through August 2025. Results: Anti-CD20 monoclonal antibodies consolidate first-line status in active disease and con-sistently reduce serum Neurofilament Light (sNfL). Anti-CD40L antibodies lower new gadolinium-enhancing lesions and produce sustained sNfL decreases in phase 2. Extended-interval natalizumab and Sphingosine-1-Phosphate (S1P) receptor modulators reduce relapses and MRI activity. CNS-penetrant Bruton’s Tyrosine Kinase (BTK) inhibitors target compartmentalized inflammation, with mixed late-phase results. Immune-reconstitution strategies provide durable disease control with rap-id, sustained sNfL suppression, while Glial Fibrillary Acidic Protein (GFAP) changes less, aligning with progression biology. EBV-directed approaches show early feasibility, with biomarker-anchored approaches; CD19 Chimeric Antigen Receptor T-cell (CAR-T) therapy remains investiga-tional. Remyelination/neurorepair candidates show signal on visual evoked potentials and myelin-sensitive MRI. Discussion: Anti-CD20 antibodies are foundational in RRMS and PPMS; S1P modulators remain effective in Relapsing Remitting Multiple Sclerosis (RRMS) and relapsing Secondary Progressive Multiple Sclerosis (SPMS). Immune-reconstitution strategies can provide durable control, while an-ti-CD40L, BTK inhibitors, EBV-directed and CD19 CAR-T, and remyelination approaches are promising but require definitive trials. Across therapies, sNfL generally decreases, whereas GFAP and smouldering-lesion MRI biomarkers often change more slowly. Conclusion: Contemporary care reliably controls inflammatory activity, but mitigating PIRA re-mains the key unmet need. Routine sNfL monitoring, complemented by GFAP and advanced imag-ing, may refine response assessment and risk stratification for progression.