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

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).

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.

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).

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.