The German Emerging Blood Biomarkers in Progressive Multiple Sclerosis (EmBioProMS) study examined neurofilament-light chain (NfL) and glial fibrillary acidic protein (GFAP) levels in patients with primary or secondary progressive MS (Abdelhak et al. Ann Clin Transl Neurol 2024;11:477-485). Mean age was 55 years; one-third of patients had no DMT exposure at the time of enrollment.

Both GFAP and NfL Z scores were significantly elevated at baseline. Higher GFAP Z scores were associated with higher EDSS scores, Timed 25-Foot Walk times and 9-Hole Peg Test times. Higher NfL levels were also associated with greater disease severity.

GFAP Z scores were similar across treatment categories. In contrast, lower NfL concentrations were found in progressive patients treated with monoclonal antibodies. In the subset for whom MRIs were available, higher GFAP and NfL Z scores were associated with a higher T2 lesion count. NfL, but not GFAP, was associated with recent contrast-enhancing lesions.

One-third of patients experienced a progression event over the mean 29-month follow-up period. Most progression events were identified with T25FW and 9HPT rather than EDSS. All progression events occurred independently of relapse activity (PIRA).

Very high GFAP Z scores (>3) were associated with a higher risk of confirmed disability progression (CDP). However, results were statistically significant only in patients with the lowest baseline NfL concentration. This suggests that GFAP, a biomarker of pathological astrocyte activation, more closely reflects PIRA. Elevated NfL was predictive of CDP, which may more closely approximate relapse-associated worsening rather than progressive biology.

The authors noted that GFAP is generally stable while NfL can vary considerably. Thus, the combination of high GFAP/lower NfL may reflect the time of sampling since GFAP is elevated at the time of a CDP event whereas NfL values tend to decrease just prior to a CDP event.