Blood markers predict MS progression

Change in serum glial fibrillary acidic protein (sGFAP) during the first 2 years of treatment predicted future risk of progression independent of relapse activity (PIRA) in 2 independent MS cohorts. Changes in GFAP concentrations post-treatment switch were more informative for PIRA risk stratification than serum neurofilament light chain (sNfL).

The effects of disease-modifying therapies (DMTs) on sGFAP are not well-established, according to Dr Ahmed Abdelhak (University of California San Francisco, CA, USA). Thus, Dr Abdelhak and colleagues conducted a study to evaluate whether changes in sGFAP or sNfL levels in the first 2 years of treatment initiation are associated with long-term PIRA risk. They analysed data from a real-world cohort of patients with MS who started either fingolimod or a B-cell depleting treatment (BCDT; ocrelizumab or rituximab).

Data from 212 fingolimod users was included; 99.5% of whom had relapsing-remitting MS. Within the first 2 years, sGFAP scores decreased in 134 patients (63.8%); mean yearly change in sGFAP was -0.09 (95% CI -0.14 to 0.04; P=0.003). Every Z-score unit reduction in sGFAP levels corresponded to a 55% lower risk of long-term PIRA with fingolimod (HR 0.45; 95% CI 0.26–0.78; P<0.001). The adjusted HR was 0.63 (95% CI 0.47–0.85; P=0.003). The corresponding adjusted HR found for NfL was 0.69 (P=0.021), but when combining NfL and GFAP in the same model, only GFAP slopes predicted protection from PIRA.

The BCDT population consisted of 269 patients with MS; 79.9% of whom had relapsing-remitting MS. In 126 patients (46.8%), sGFAP scores decreased in the first 2 years of treatment. For every Z-score unit reduction in sGFAP levels, HR for PIRA was 44% lower (HR 0.56; 95% CI 0.32-0.98; P=0.041). The adjusted HR was 0.56 (95% CI 032–0.92; P=0.001). Again, when combining NfL and GFAP in a single model, only GFAP slopes predicted PIRA protection.

Dr Abdelhak added that in the fingolimod group, stable/increasing GFAP is a sign of poor prognosis, whereas in the BCDT group, increasing GFAP is a poor prognostic sign. He concluded that monitoring of sGFAP dynamics following DMT initiation could be used to prognosticate long-term PIRA risk and provide valuable insights for trial design and interpretation.

1. Abdelhak A, et al. Treatment-associated changes in serum glial fibrillary acidic protein and neurofilament light chain levels and risk of disability progression independent of relapse activity in multiple sclerosis. Abstract O131, ECTRIMS 2024, 17–20 October 2024, Copenhagen, Denmark.

Medical writing support was provided by Michiel Tent
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Posted on 25 September 202425 September 2024