Blood markers predict MS progression

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

High sGFAP can help predict disability progression in MS, and GFAP levels can more accurately predict PIRA than relapse-associated worsening (RAW). However, the effects of disease-modifying treatments (DMTs) on sGFAP levels are not well-established, according to Dr Ahmed Abdelhak (University of California San Francisco, CA, USA) [1]. 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 [1]. 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).

The fingolimod population included 212 patients; 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 sNfL was 0.69 (P=0.021); but when combining sNfL and sGFAP in the same model, only sGFAP 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 0.32–0.92; P=0.001). Again, when combining sNfL and sGFAP in a single model, only sGFAP slopes predicted PIRA protection.

Dr Abdelhak added that stable and increasing sGFAP were signs of poor prognosis in the fingolimod group. In the BCDT group, increasing sGFAP was 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. Changes in sGFAP concentrations after the treatment switch were more informative for PIRA risk stratification than changes in sNfL.

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, 18–20 September, Copenhagen, Denmark.

 

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Posted on 18 November 2024