According to study results published in JAMA Neurology, serum glial fibrillary acidic protein (GFAP) levels may help identify people with multiple sclerosis (MS) at higher risk for progression independent of relapse activity (PIRA). The findings support a complementary role for GFAP alongside neurofilament light chain (NfL), with NfL more closely associated with relapse activity and GFAP more closely associated with progression risk. 

Researchers analyzed data from 2 large prospective MS cohorts: the Swiss Multiple Sclerosis Cohort (SMSC; NCT02433028) and the Expression, Proteomics, Imaging, Clinical (EPIC) study. The analysis included 2329 individuals with MS with a total of 18,629 total serum biomarker measurements. The SMSC cohort included 1709 individuals with a median follow-up of 6.9 years, while the EPIC cohort included 620 individuals with a median follow-up of 13.1 years. Serum NfL and GFAP z scores were calculated every 6 or 12 months and assessed in relation to relapse risk, long-term PIRA, short-term PIRA, and treatment-associated biomarker changes. 

Key results include the following: 

  • Elevated NfL was associated with approximately 2-fold higher risk of relapse within the following year in SMSC and showed a similar association in EPIC. 

  • Elevated GFAP, defined as a z score >1.0, was associated with higher short-term PIRA risk during the subsequent visit interval in both SMSC (HR, 1.45; 95% CI, 1.21 to 1.75; P<.001) and EPIC (HR, 1.36; 95% CI, 1.07 to 1.71; P=.01). 

  • Baseline GFAP elevation was associated with a 31% higher risk of future PIRA across the full observation period in SMSC (HR, 1.31; 95% CI, 1.08 to 1.58; P=.005), with a similar but nonsignificant trend in EPIC. 

  • In SMSC, each yearly unit reduction in GFAP z score during the first 2 years of fingolimod or B-cell–depleting therapy was associated with lower subsequent PIRA risk, with risk reductions of 54% and 67%, respectively. 

  • NfL slope during treatment was not significantly associated with subsequent PIRA in either treatment cohort. 

Although the findings suggest GFAP may help with individualized risk stratification and monitoring of treatment response in MS, researchers noted several limitations, including differences in PIRA definitions between cohorts, limited generalizability to more racially and ethnically diverse populations, and the observational design of the study. 

Source: Einsiedler M, Sandgren S, Schaedelin S, et al. Serum glial fibrillary acidic protein dynamics, disease progression, and therapy response in multiple sclerosis. JAMA Neurol. Published online August 3, 2026. doi:10.1001/jamaneurol.2026.2500