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

Clinical Snapshot

Key Findings

• P Value: p=0.0023 (fingolimod), p=0.0487 (BCDT)

• Effect Size: Hazard ratio 1.27 for fingolimod cohort, 1.19 for BCDT cohort (per Z-score increase)

• Primary Outcome: Time to progression independent of relapse activity (PIRA)

• Nnt Or Sensitivity: Strong platform correlation r=0.94 between Elecsys and Simoa assays

• Confidence Interval: 95% CI: 1.09-1.48 (fingolimod), 1.00-1.40 (BCDT)

Clinical Application

High feasibility with Elecsys platform widely available in clinical laboratories, Z-score standardisation enables routine implementation Relevant to Australian MS management under PBS-subsidised treatments; could inform TGA biomarker guidance and RACGP neurological referral criteria Adults with multiple sclerosis, particularly those on disease-modifying therapies requiring progression monitoring

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: GFAPSimoa and GFAPElecsys measurements were correlated (r=0.94), with Elecsys values ∼54 % lower (GFAPElecsys, ng/L=2.847 [95 % confidence interval, CI: 1.335 - 4.98] + 0.457 [0.434 - 0.478] * GFAPSimoa, ng/L). In univariable Cox models, GFAPSimoa and GFAPElecsys Z scores were associated with time-to-PIRA in both validation cohorts. In multivariable Cox models, higher GFAPSimoa 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, GFAPElecsys 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 GFAPSimoa Z scores can be successfully bridged to GFAPElecsys Z scores, supporting Elecsys`s potential for clinical implementation.