Prognostic value of neurofilament light chain protein and glial fibrillary acidic protein in multiple sclerosis subtypes and disease activity patterns: a systematic review and meta-analysis.

BACKGROUND

Neurofilament light chain protein and glial fibrillary acidic protein have been proposed as potential blood biomarkers for multiple sclerosis. However, their diagnostic and prognostic values across different subtypes and disease activity patterns remain unclear.

METHODS

We systematically searched major databases (inception to February 13, 2025). A total of thirteen studies including 4,016 individuals were incorporated. A random-effects meta-analysis methodology was applied to assess the forecasting capabilities of NfL and GFAP concerning multiple sclerosis relapses and the advancement of disability. Subgroup examinations were executed according to disease classifications and the observed activity levels.

RESULTS

Treated as a continuous measure, NfL exhibited a 4% increase in risk for adverse events with each individual unit escalation (RR = 1.04, 95% CI: 1.01-1.06, P < 0.001). Subgroup analyses revealed that predictive power was stronger in RRMS compared with mixed type (RR = 3.82 vs. 1.03, P < 0.01), and was statistically significant for neurodegenerative progression (EDSS worsening without inflammation) (RR = 1.03, P < 0.05). Using a threshold, NfL levels above the cutoff increased risk 2.61-fold (RR = 2.61, 95% CI: 1.74-3.92). GFAP showed no significant overall prognostic value (RR = 1.01, P = 0.18), with no subgroup differences.

CONCLUSION

NfL is a sensitive biomarker for RRMS and neurodegenerative progression, with its value dependent on subtype and activity pattern. No evidence supports GFAP as an independent prognostic marker. Precise MS subtyping is crucial for clinical biomarker application.