Using Plasma NfL and GFAP to Monitor Response to Anti-CD20 Treatment in MS
Robert Gross1, Stefan Sillau1, Sean Selva1, Alanna Ritchie1
1University of Colorado
Objective:
To compare changes in plasma concentrations of Neurofilament light (NfL) and Glial Fibrillary Acidic Protein (GFAP) in individuals with relapsing multiple sclerosis (RMS) vs progressive multiple sclerosis (PMS), treated with anti-CD20 immunotherapy (rituximab or ocrelizumab)
Background:
Blood biomarkers, especially NfL, can augment clinical and radiographic data in MS treatment monitoring. Few studies have investigated longitudinal change in NfL or GFAP in PMS patients taking anti-CD20s or compared changes in these biomarkers between RMS and PMS.
Design/Methods:
Subjects were selected by MS diagnosis, anti-CD20 treatment for at least 6 months, and presence of multiple blood samples in our Center’s Biorepository. Demographic/clinical information was extracted by chart review. SIMOA plasma assays of NfL and GFAP were conducted at baseline and follow-up (between 3 and 12 months) on Quanterix SR-X. Biomarker concentrations were log transformed. Summary statistics and longitudinal regression analyses, correcting for age, were generated.
Results:
37 subjects and 67 samples were analyzed (n=7 had no follow-up samples between 3 and 12 months). 64.9% were female. RMS (n=19) had mean(SD) age 38.7(9.2). PMS (n=18) had mean age 56.1(10.4). Age-adjusted mean concentrations of NfL and GFAP did not differ significantly between RMS and PMS at baseline. Geometric mean NfL declined between baseline (6.8, 95%CI 4.2-11.0) and follow-up (4.9, 95%CI 3.3-7.3) in RMS but stayed stable in PMS. Geometric mean GFAP increased between baseline (52.4, 95%CI 35.2-77.9) and follow-up (60.8, 95%CI 40.4-91.4) in PMS but stayed stable in RMS. The changes for both NfL and GFAP differed statistically significantly between MS types.
Conclusions:
With anti-CD20 treatment, plasma NfL levels decreased in RMS by 27.6% while staying stable in PMS; GFAP levels increased in PMS by 16% while remaining stable in RMS. Results correlate with clinical evidence showing greater benefit of anti-CD20 immunotherapy in RMS compared to PMS. Future studies will include more subjects, longer observation, and different immunotherapies.