Th129 - Serum Neurofilament Light Chain (NfL)and CSF Glial Fibrillary Acidic Protein (GFAP) Together Improve the Prediction of Long-term Clinical Progression in Multiple Sclerosis
Abstract Text: Objective To evaluate the individual and combined prognostic utility of the protein biomarkers NfL and GFAP in serum and CSF from samples obtained in early MS to predict disability progression (CDP).
Methods Paired serum and CSF samples within 5 years of MS onset with >15 years of follow-up were included. NfL and GFAP were measured by SiMOA. We converted raw sNfL to age-adjusted percentiles using normative Swiss data from >5000 controls. CDP was defined by sustained EDSS score worsening between 6 monthly follow-up visits.
Results: Sixty patients were included and followed for a mean of 15.8 years (s.d. 2.5). 25 developed CDP. Serum NfL was strongly correlated to CSF levels (r=0.86, 95% CI 0.78-0.92), while serum GFAP had a weaker correlation with CSF (r=0.05, 95% CI 0.29-0.67). In ROC curve analysis, age-adjusted serum NfL (AAsNfL) and CSF GFAP (cGFAP) were the two strongest predictors of CDP at 15 years (ROC curve AUC 0.77, p=0.0004 and AUC 0.64, p=0.001). Serum GFAP was not predictive. In a Cox Proportional Hazard Regression, each percentile increase in baseline AAsNfL and cGFAP was associated with a 2.5% and 1.4% increased risk of developing CDP after adjustment for baseline EDSS score. Comparing the 13 patients in the highest quintile for both AAsNfL and cGFAP with the 17 patients in the lowest quintiles, there was a 7.3x risk of developing CDP (95% CI 1.4-10.9) (log-rank p=0.00093).
Interpretation: The combination of sNfL with cGFAP improved the prediction of CDP compared to either marker considered in isolation.
