Serum neurofilament light chain as a biomarker for monitoring the therapeutic response of disease-modifying therapies in patients with relapsing-remitting multiple sclerosis
Initiation of DMTs in RRMS patients was associated with a significant decrease in sNfL levels, suggesting reduced neuroaxonal damage following treatment introduction, and monitoring sNfL may represent a useful non-invasive biomarker of biological treatment response in RRMS patients.
Abstract
Background/Aim. Serum neurofilament light chain (sNfL) is a sensitive biomarker of neuroaxonal damage and disease activity in multiple sclerosis (MS). The aim of this study was to investigate changes in sNfL levels following initiation of different disease-modifying therapies (DMTs) in treatment-naive patients with relapsing-remitting MS (RRMS), and to explore potential sex-related differences in treatment response. Methods. The longitudinal study analyzed 78 treatment-naive RRMS patients (40 males, 38 females) initiating their first DMT [injectable (n = 37): interferon beta-1a: Rebif®, interferon beta-1b: Betaferon®, glatiramer acetate: Copaxone®, or oral (n = 41): sphingosine 1-phosphate receptor (S1PR) modulators: fingolimod, ozanimod, ponesimod]. Concentrations of sNfL were measured using enzyme-linked immunosorbent assay - ELISA prior to therapy initiation and after 6 months. Disability was assessed at baseline using Expanded Disability Status Scale - EDSS and Multiple Sclerosis Severity Score - MSSS. Repeated measures analysis was used to evaluate longitudinal changes. Results. A significant reduction in sNfL levels was observed after 6 months of DMT therapy in the examined patients (p < 0.001; partial η2 = 0.358). A significant interaction between sex and treatment response was found (p = 0.003), with a more pronounced reduction in sNfL levels observed in females. No significant difference in sNfL reduction was found between injectable therapies and S1PR modulators (p = 0.092), although baseline sNfL levels were higher in the S1PR group (p < 0.001). Conclusion. Initiation of DMTs in RRMS patients was associated with a significant decrease in sNfL levels, suggesting reduced neuroaxonal damage following treatment introduction. Higher baseline sNfL levels in females may indicate potential sex-related differences in neuroaxonal injury. Monitoring sNfL may represent a useful non-invasive biomarker of biological treatment response in RRMS patients.
Failure to reduce zNfL levels after 1 year of treatment was associated with subsequent disease activity, even in patients otherwise considered stable, providing complementary information to clinical and MRI-based monitoring.
Victoria Fernández, A. Pappolla, P. Carbonell-Mirabent et al.· Neurology· 1 citation
Abstract Objectives Serum neurofilament light chain (sNfL) reflects neuroaxonal injury in relapsing-remitting multiple sclerosis (RRMS), but its clinical utility is limited by high interindividual variability and confounders such as renal function. Population-based thresholds may therefore be suboptimal for longitudina...
S. de las Heras Flórez, Gema García de la Rosa, Vicente Martín García et al.· Clinical Chemistry and Labor...· 1 citation
The longitudinal zNfL changes were related to lesion activity and subsequent atrophy, even after including MRI measures, and cross-sectional zNfL was related to active disease and predictive of disease progression, but not after taking MRI measures into account.
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