Clinical Characteristics Associated With High Baseline Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL) Levels in Patients With Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD) From the PREVENT and CHAMPION-NMOSD Trials
Dean Wingerchuk1, Jeffrey Bennett2, Jin Nakahara3, Jerome De Seze4, Makoto Kinoshita5, Stacey Clardy6, Kerstin Allen7, Ruba Bou-Chahine7, Becky Parks7, Jeannette Stankowski7, Sean Pittock1
1Mayo Clinic, 2University of Colorado Anschutz Medical Campus, 3Keio University School of Medicine, 4CHU de Strasbourg, 5Osaka University, 6University of Utah Health, 7Alexion, AstraZeneca Rare Disease
Objective:
Evaluate associations between baseline GFAP and NfL serum levels, clinical characteristics, and time to first adjudicated on-trial relapse in PREVENT (NCT01892345) and CHAMPION-NMOSD (NCT04201262).
Background:
The placebo-controlled PREVENT and externally controlled CHAMPION-NMOSD trials evaluated the efficacy and safety of eculizumab and ravulizumab, respectively, in adults with AQP4-Ab+ NMOSD. Compared with healthy donors, patients from both trials had elevated baseline GFAP and NfL levels (biomarkers of astrocyte and neuronal injury, respectively), which decreased following treatment.
Design/Methods:
Clinical data and available serum samples from PREVENT (41 of 143 patients) and CHAMPION-NMOSD (55 of 58 patients) were used in multivariable logistic regression models to identify independent statistical predictors of high GFAP and NfL levels. A test (CHAMPION-NMOSD) and validate (PREVENT) strategy was applied. Kaplan-Meier curves and log-rank tests evaluated the association between GFAP and NfL levels and time to first adjudicated on-trial relapse in PREVENT.
Results:
High GFAP levels in CHAMPION-NMOSD were associated with higher age at initial presentation (odds ratio [OR]=3.64, P=0.001), shorter time since last relapse (OR=3.10, P=0.020), and higher baseline Hauser Ambulation Index (HAI) score (OR=2.25, P=0.010); similar findings were observed for the latter two characteristics in PREVENT (P<0.08). High NfL levels in CHAMPION-NMOSD were associated with higher age at first dose (OR=4.93, P=0.005) and higher baseline HAI score (OR=4.38, P=0.017); similar findings were observed in PREVENT (P<0.10). No association was found between baseline GFAP and NfL levels and time to first adjudicated on-trial relapse in PREVENT. No relapses were observed in patients treated with ravulizumab in CHAMPION-NMOSD despite several patients presenting with high baseline GFAP and/or NfL levels.
Conclusions:
In this analysis, high baseline GFAP and NfL levels in PREVENT and CHAMPION-NMOSD serum samples were associated with clinical characteristics related to age and ambulation. No associations were observed between levels of these biomarkers and relapse risk or time to first adjudicated on-trial relapse.
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