Serum GFAP as a biomarker for progression in multiple sclerosis: assay comparison and a large reference database of healthy controls

Abstract Objectives Compare Elecsys (Roche) and Simoa (Quanterix) immunoassays for serum glial fibrillary acidic protein (GFAP) using our reference database and Z scores, and evaluate their prognostic value for progression independent of relapse activity (PIRA) in multiple sclerosis (MS). Methods Platform correlation was assessed in 612 samples from healthy controls (n=188; median [interquartile range, IQR] age 45.1 [36.4–61.7] years) and people with MS (n=424; 45.3 [35.2–53.9] years). Elecsys values were converted to Z scores via Passing-Bablok-derived regression and validated in fingolimod (n=414), and B-cell depleting therapy (BCDT; n=353) cohorts. Z scores and hazard ratios (HRs) for time-to-PIRA were compared using Cox regression. Results GFAP Simoa and GFAP Elecsys measurements were correlated (r=0.94), with Elecsys values ∼54 % lower (GFAP Elecsys , ng/L=2.847 [95 % confidence interval, CI: 1.335 – 4.98] + 0.457 [0.434 – 0.478] * GFAP Simoa , ng/L). In univariable Cox models, GFAP Simoa and GFAP Elecsys Z scores were associated with time-to-PIRA in both validation cohorts. In multivariable Cox models, higher GFAP Simoa Z scores were associated with shorter time-to-PIRA in fingolimod cohort (HR: 1.27 [95 % CI 1.08 – 1.50], p=0.0031) and trended toward significance in BCDT (1.18 [0.99 – 1.41, p=0.0693). In contrast, GFAP Elecsys Z scores were associated with time-to-PIRA in both cohorts (fingolimod: 1.27 [1.09 – 1.48], p=0.0023; BCDT: (1.19 [1.00 – 1.40], p=0.0487). Conclusions Serum GFAP measured by Elecsys shows a comparable association with time-to-PIRA as Simoa, and GFAP Simoa Z scores can be successfully bridged to GFAP Elecsys Z scores, supporting Elecsys`s potential for clinical implementation.