This prospective observational cohort study evaluated whether serum GFAP levels — and treatment-related changes in GFAP — predict future progression independent of relapse activity (PIRA) in MS, using two large cohorts (SMSC, n=1,709; EPIC, n=620) with up to 13 years of follow-up and 18,629 total measurements.
Elevated serum GFAP (z score >1.0, 84th percentile) was associated with ~40% higher short-term PIRA hazard in both cohorts (SMSC: HR 1.45, 95% CI 1.21–1.75; EPIC: HR 1.36, 95% CI 1.07–1.71). Each unit yearly reduction in GFAP z score during the first 2 years on fingolimod or B-cell-depleting therapy was linked to 54% and 67% lower PIRA risk, respectively. GFAP-based trial enrichment could cut required sample sizes by ~20%.
- Both cohorts are from tertiary MS centers, which may limit generalizability to broader MS populations. - Treatment-associated GFAP changes are observational; causality cannot be established. - Full text was not accessible for detailed review of covariate adjustment and subgroup analyses.
Consider monitoring serum GFAP alongside NfL in persons with MS — elevated GFAP flags higher near-term PIRA risk and may help guide treatment intensity. Meaningful drops in GFAP on fingolimod or B-cell-depleting therapy appear to signal a more favorable progression outlook.
