High sGFAP levels are associated with disease progression, independent of NfL or relapse activity

In MS patients on B-cell-depleting therapy (BCDT), high levels of serum glial fibrillary acidic protein (sGFAP) may indicate an increased risk of disease progression, independently of serum neurofilament light chain (sNfL) levels. Increased sGFAP Z-scores may be a good efficacy measure for novel MS treatments.

GFAP is a structural protein of astrocytes, so its serum levels indicate astrocyte activation and/or damage. NfL is a structural protein of neurons, and serum levels indicate neuro-axonal damage. Dr Pascal Benkert (University Hospital Basel, Switzerland) and colleagues investigated whether these biomarkers reflect treatment response and are associated with disease progression in MS patients using BCDTs [1]. They also compared the biomarker profiles of patients with and without progression independent of relapse activity (PIRA), using sGFAP Z-scores based on a reference database of healthy controls.

The Swiss research group set up a study including 322 participants of the Swiss MS Cohort who started treatment with ocrelizumab or rituximab. Of these patients, 242 (75%) had relapsing-remitting MS, and 80 (25%) had progressive MS. Median Expanded Disability Status Scale (EDSS) score was 3, median follow-up was 4.1 years.

Figure: Increased sNFL and sGFAP levels prognosticate PIRA [1]



PIRA, progression independent of relapse activity; sGFAP, serum glial fibrillary acidic protein; sNfl, serum neurofilament light chain.

In a time-to-event analysis, there was a trend towards an association between increased sNfL levels (Z-score >1) and risk of PIRA (HR 1.5; 95%CI 0.9–2.4), and a clear association between high sGFAP levels (Z-score >1) and risk of PIRA (HR 2.1; 95%CI 1.3–3.3) (see Figure). In a model combining both markers, sGFAP levels were independently associated with risk of PIRA (HR 1.9; 95% CI 1.3–3.2; P=0.38). The results of a longitudinal analysis found older age to be associated with increased sNfL levels during BCDT (indicating higher disease activity at a younger age). Interestingly, in non-PIRA, sNfL levels were reduced (-0.98; P<0.001); sNfL levels remained elevated in patients experiencing PIRA (+0.95; P_inter=0.008). sGFAP levels increased in all patients (interaction was not significant) and increased more in patients with PIRA (P=0.023).

Dr Benkert concluded that sGFAP is a promising marker of disease progression, independent of sNfL.

1. Benkert P, et al. Serum glial fibrillary acidic protein (GFAP) is a longitudinal indicator of disease progression in MS while neurofilament light chain (NfL) associates with therapy response in patients under B-cell depleting therapy. O077, MSMilan 2023, 11–13 October, Milan, Italy.

 

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Posted on 4 December 20234 December 2023