In neuromyelitis optica spectrum disorder (NMOSD), no blood tests to evaluate disease activity, attack severity, or therapy impact have been developed. For a study, the researchers determined the effects of inebilizumab medication on serum glial fibrillary acidic protein (sGFAP) concentration and NMOSD activity. The N-MOmentum clinical trial in adults with NMOSD was a prospective, multicenter, double-blind, placebo-controlled, randomized clinical experiment. Single-molecule arrays (SIMOA) were used to evaluate sGFAP levels in 1,260 serial and attack-related samples from 215 N-MOmentum participants (92% of whom were aquaporin 4-immunoglobulin G-seropositive) as well as control samples (from healthy donors and patients with relapsing-remitting multiple sclerosis). Sixty-two participants (29%) had high sGFAP concentrations at baseline (≥170pg/ml; equal or more than 2 standard deviations above healthy donor mean concentration) and were more likely to have an adjudicated attack than those who had lower baseline concentrations (hazard ratio [95% CI], 3.09[1.6-6.1], P = 0.001). Within a week of an attack, median (interquartile range [IQR]) concentrations increased (baseline:168.4, IQR = 128.9-449.7 pg/ml; attack: 2,160.1, IQR = 302.7-9,455.0pg/ml, P = 0.0015) and were correlated with attack severity (median fold change from baseline [FC], minor attacks:1.06, IQR = 0.9-7.4; major attacks: 34.32, IQR = 8.7-107.5, P = 0.023). This attack-related rise in sGFAP was mostly determined in placebo-treated subjects (FC: 20.2, IQR = 4.4-98.3, P = 0.001), but not in ibalizumab-treated participants (FC:1.1, IQR = 0.8-24.6, P > 0.05). GFAP levels in the blood could be used as a biomarker for NMOSD activity, attack risk, and therapy outcomes.