Results of a post hoc analysis of phase 3 trials of Zeposia (ozanimod; Bristol Myers Squibb, New York, NY) showed that higher baseline plasma concentrations of glial fibrillary acidic protein (GFAP)—a marker of astrocytic activation—were associated with greater disease severity and increased relapse risk in individuals with relapsing multiple sclerosis (RMS). The findings support the potential role of GFAP as a biomarker of baseline disease severity independent of relapse activity in RMS, as well as treatment response.

This study included a pooled analysis from the phase 3 SUNBEAM (NCT02294058) and RADIANCE (NCT02047734) clinical trials which compared daily oral treatment with ozanimod 0.46 mg or 0.92 mg with once weekly intramuscular interferon (IFN) β-1a 30 µg. In both trials, ozanimod treatment began with a 7-day dose escalation: 0.23 mg daily on days 1 through 4, followed by 0.46 mg daily on days 5 through 7, before transitioning to the assigned maintenance dose of either 0.46 mg or 0.92 mg starting on day 8. Plasma GFAP was measured at baseline using the single molecule array (Simoa) platform. Researchers assessed associations between baseline GFAP and both baseline characteristics and on-treatment outcomes using robust regression models and multivariable lasso modeling.

Key findings include the following:

  • Baseline plasma GFAP levels were positively associated with age, neurofilament light chain (NfL) levels, gadolinium-enhancing and T2 lesion counts, and Expanded Disability Status Scale (EDSS) scores (all nominal P<.0001).
  • At month 12, higher GFAP levels were inversely associated with whole brain volume (WBV) and the likelihood of achieving no evidence of disease activity (NEDA-3).
  • Elevated baseline GFAP levels were associated with more relapses through month 12 inSUNBEAM (P<.0001) participants and month 24 in RADIANCE (P=.0003) participants; in lasso modeling, it remained an independent predictor of relapse risk through month 12 only.
  • Baseline GFAP levels were associated with higher EDSS scores at month 12 (P=.0002) and more gadolinium-enhancing (P<.0001) and new/enlarging T2 lesions (P<.0001) at month 12.
  • GFAP was not an independent predictor of MRI lesion burden, brain volume, or EDSS score in multivariable models.

Source: Harris S, Comi G, Cree BAC, et al. Glial fibrillary acidic protein as a marker of disease in relapsing multiple sclerosis: post hoc analysis of phase 3 ozanimod trials. Eur J Neurol. 2025;32(6):e70222. doi:10.1111/ene.70222