To compare how serum glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) correlate with progression and acute inflammation in multiple sclerosis (MS).

There are insufficient diagnostic tools to anticipate ‘pure progression’ and acute inflammation in MS. 

sGFAP and sNfL were measured using Simoa assays in three cohorts of patients of the Swiss MS Cohort: 1) worsening progressive MS (wPMS; 184 samples (s)/18 patients (p), median follow-up (FU): 6.5 years (y), median EDSS baseline (BL)/last visit 4.0/6.0); 2) clinically stable MS (stMS; 169s/19p, 7.1 y, EDSS 3.0/2.5) (both relapse-free during FU); 3) Relapsing MS (132s/66p) during a) acute disease activity (relapse/contrast enhancing lesions); 66s) and b) stable phase (66s); and healthy controls (HC; 485s/259p; BL and 1y FU). Multivariable mixed models were applied to longitudinally compare log-transformed sGFAP/sNfL between groups 1) versus 2); 3a) versus 3b); and adjusted mixed/Cox regression models for the association between BL sGFAP/sNfL levels and brain volume loss (BVL) and time to confirmed disability worsening (CDW) in groups 1) and 2). 

sGFAP increased in HC with age (1.5%/y, p<0.001), decreased with body mass index (-1.1%/BMI unit, p=0.015) and was 15% higher in women than men (p=0.004). wPMS patients showed 57% higher sGFAP levels versus stMS (p=0.006) and remained 51% higher after sNfL adjustment in the model (p=0.010). In contrast, the 25% increase of sNfL in wPMS versus stMS (p=0.046) disappeared after sGFAP adjustment. Acute disease activity had no effect on sGFAP, while it increased sNfL by 53% (p<0.001). Higher sGFAP at BL was associated with accelerated gray matter BVL (per doubling (pd): 0.24%, p<0.0001), but not white matter (p=0.48). sGFAP, but not sNfL levels were associated with shorter time to CDW (HR pd: 3.63, p=0.006; HR pd: 1.90, p=0.112). 

sGFAP may be a more specific biomarker for ‘pure progression’ than sNfL.