Plasma glial fibrillary acidic protein and neurofilament light chain in relation to disability worsening in multiple sclerosis

Background: Predicting disability worsening in multiple sclerosis (MS) remains an important challenge. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) seem promising biomarkers. Studies investigating blood GFAP in relation to longitudinal outcome measures in MS are scarce. Objective: To compare plasma-GFAP (p-GFAP) and plasma-NfL (p-NfL) levels in relation to sustained disability worsening. Methods: We measured baseline p-GFAP and p-NfL in a prospective cohort of 115 individuals with MS and 30 matched controls, using Single Molecule Array (Simoa). Disability worsening was defined as an increase in at least one of three measures (Expanded Disability Status Scale, Timed 25-foot walk, 9-Hole Peg test), confirmed after 6 months and persistent upon data closure. Results: In a multivariable Cox proportional-hazards model, p-GFAP was not significantly associated with sustained disability worsening after 4.40 +/- 0.82 years, while p-NfL (HR = 1.046, p = 0.001), EDSS (HR = 1.24, p = 0.039), and disease duration (HR = 1.048, p = 0.017) were. Area under the curve of ROC curves in relation to worsening was 0.61 for p-GFAP (p = 0.031) and 0.63 for p-NfL (p = 0.015). Kaplan-Meier curves showed similar patterns for both proteins. Conclusion: p-NfL emerged as a significant explanatory variable for worsening in Cox regression analysis, and p-GFAP did not. Both p-GFAP and p-NfL were related to worsening based on ROC curves.