Glial Fibrillary Acidic Protein as a Marker of Disease in Relapsing Multiple Sclerosis: Post Hoc Analysis of Phase 3 Ozanimod Trials.

BACKGROUND

This post hoc analysis investigated relationships between baseline plasma glial fibrillary acidic protein (GFAP), a potential biomarker for multiple sclerosis (MS), and baseline characteristics and on-treatment outcomes in participants with relapsing MS (RMS) from two Phase 3 trials that randomly assigned ozanimod 0.46 mg or 0.92 mg or interferon β-1a 30 μg.

METHODS

In the Phase 3 trials (SUNBEAM [ClinicalTrials.gov: NCT02294058; EudraCT: 2014-002320-27], duration: ≥ 12 months; and RADIANCE [ClinicalTrials.gov: NCT02047734; EudraCT: 2012-002714-40], duration: 24 months) baseline plasma GFAP was measured via Simoa (Quanterix). Adjusted regression models were used to determine relationships between baseline GFAP and baseline participant characteristics and to predict on-treatment outcomes.

RESULTS

Baseline GFAP was associated with sex and had inverse associations with baseline body mass index and whole brain volume (WBV). Baseline GFAP had positive associations with baseline age, neurofilament light chain, numbers of gadolinium-enhancing (GdE) and T2 lesions, and Expanded Disability Status Scale (EDSS) score. Baseline GFAP had inverse associations with on-treatment WBV and the proportion of participants with no evidence of disease activity-3. Baseline GFAP had positive associations with on-treatment number of relapses through Months 12 and 24, number of GdE lesions at Month 12, number of new/enlarging T2 lesions over 12 months, and Month 12 EDSS score. In a multivariable lasso model, baseline GFAP concentration independently predicted only the number of relapses through Month 12.

CONCLUSIONS

These data suggest that plasma GFAP is a relapse-independent metric of baseline disease severity and a predictor of treatment response in participants with RMS.