Change in serum glial fibrillary acidic protein (sGFAP) during the first 2 years of treatment predicted future risk for progression independent of relapse activity (PIRA) in two 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 Ahmed Abdelhak, MD, from the University of California San Francisco. 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. The researchers analyzed data from a real-world cohort of patients with MS who started either fingolimod or a B-cell depleting treatment (BCDT; ocrelizumab or rituximab).1
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 for 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.
Medical writing support was provided by Michiel Tent
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