Putting biomarkers into practice


ACTRIMS Forum 2023

Neurofilament-light chain (NfL) and glial fibrillary acidic protein (GFAP) have the potential to be useful biomarkers of axonal damage and neurodegeneration. However, additional research is needed to determine normative values and to track the significance of biomarker changes over time. A number of groups addressed these issues at the Americas Committee for Treatment and Research in MS (ACTRIMS) Forum 2023, held February 23-25, 2023 in San Diego CA.

The MS PATHS group examined published reference values used to stratify NfL levels in MS patients (Sotirchos et al. ACTRIMS Forum 2023;P028).  The analysis involved 12,730 blood samples from 6635 MS patients. Mean NfL level was 12.88 pg/mL. NfL values classified as elevated ranged from 2.5% to 30.9% depending on the reference used. The group suggested that comparing NfL changes over time in individual patients would be more useful.

This approach was used in a study by the University of Ottawa (Thebault et al. ACTRIMS Forum 2023;P038). A reference change value (RCV) was calculated from serial NfL measures in individual patients (see RCV tool at BMJ 2020;368:m149: www.bmj.com/content/368/bmj.m149/rr-8). Serum NfL was obtained every three months in 58 MS patients over one year. In comparing patients with and without MRI lesions, median RCV was 57 and 92, respectively. An RCV using a cut-off of >76 was predictive of new MRI lesions (sensitivity 60%, specificity 75%). A 10-unit increase in RCV was associated with a 30% increase in the odds of new MRI activity.

The Ottawa group also examined the change in NfL + GFAP over time as a prognostic measure (Thebault et al. ACTRIMS Forum 2023;P041). A total of 60 patients with >15 years of follow-up were included (mean 15.8 years); 42% had 6-month confirmed disability progression (CDP) during the observation period. Age-adjusted sNfL and cGFAP were the strongest predictors of disability. Each percentile increase in sNfL and cGFAP from baseline was associated with a 2.5% and 1.4% increase in CDP risk.

A separate study looked at reference ranges for NfL and GFAP in healthy controls (n=145) (Borko et al. ACTRIMS Forum 2023;P018). Mean sNfL level was 2.48 pg/mL at ages 15-19 years, 7.25 pg/mL at ages 50-59 years, and 19.55 pg/mL at ages 80-85 years. Mean GFAP increased from 49.99 pg/mL at ages 15-19 years to 70.71 pg/mL at ages 50-59 years to 121.77 at ages 80-85 years. NfL increased by 2.78% per year of age (females 2.72%, males 2.83%). GFAP increased by 1.53% per year of age (females 1.49%, males 1.64%). NfL and GFAP levels were lower with increasing body-mass index (1.65% and 1.44%, respectively, per unit of BMI).

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