Serum glial fibrillary acidic protein predicts disease progression in multiple sclerosis

Objective

Glial fibrillary acidic protein (GFAP) is expressed in astrocytes and may be a useful marker of non-active progressive multiple sclerosis (MS). We evaluate serum GFAP (sGFAP) in a large cohort of MS patients to determine if it predicts progression independent of relapse activity (PIRA), future gait aid, and conversion to secondary progressive disease (SPMS).

Methods

Adults with clinically isolated syndrome or any subtype of MS who were listed in the Brigham MS Center Research Database and had at least one sGFAP result were included. All clinic visits following first sample were analyzed for PIRA, future gait aid, and conversion to SPMS. Future cognitive dysfunction and fatigue were evaluated as secondary outcomes.

Results

In total, 741 patients were included (average age: 42.3, average disease duration: 3.7 years, median EDSS: 2, and median follow-up duration: 10.0 years). Of 643 patients (86.8%) without progressive disease at baseline, 15.9% developed SPMS. Among all 741, 50.5% had PIRA and 18.6% developed a gait aid requirement. sGFAP level predicted PIRA, future gait aid, and conversion to SPMS in univariable models (p < 0.001, <0.001, and 0.002). sGFAP remained predictive for PIRA and future gait aid in multivariable models in those younger than 50 (p = 0.048, 0.003). Change in sGFAP level over time was not predictive. There was no association between sGFAP and future fatigue or cognitive dysfunction.

Interpretation

sGFAP helps to predict PIRA, future gait aid, and conversion to SPMS in a large cohort of MS patients. Our data suggest that baseline levels may be more useful than the change over time.