Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Differential Biomarkers of Response to Dimethyl Fumarate and Ocrelizumab in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease. Quantify- ing neuronal damage is a critical step for patient care. Neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are the most promising serum biomarkers reflecting neuronal damage and astroglial activation, respectively. This study analyzed sNfL and sG- FAP in 177 MS patients and 71 healthy controls (HCs) using SIMOA technology, classifying patients as responders (Rs) or non-responders (NRs) based on “No Evidence of Disease Activity 3” (NEDA-3) status during two years of treatment. Longitudinal analyses were per- formed for Dimethyl fumarate (DMF) and Ocrelizumab (OCRE) treatment. Biomarker–age correlation analysis in HCs confirmed correlation between both NfL and GFAP, with age and cut-off values specific for age decades being calculated. Both biomarkers were higher in MS patients compared to HCs. sNfL showed a significant increase in NR patients overall. In contrast, sGFAP was elevated in the low-to-moderate-efficacy treatment agents (LETAs) NR group and also in the DMF NR subgroup, suggesting that it monitors persistent astrogliosis. Longitudinal analysis showed that both biomarkers decreased during DMF treatment after one year. During OCRE treatment, sNfL rapidly reduced to HC levels within one year, while sGFAP decreased only after two years. This highlights that OCRE acts differently on the pathological processes linked to the two biomarkers.