TY - JOUR
T1 - Serum Glial Fibrillary Acidic Protein
T2 - A Neuromyelitis Optica Spectrum Disorder Biomarker
AU - the N-MOmentum scientific group and the N-MOmentum study investigators
AU - Aktas, Orhan
AU - Smith, Michael A.
AU - Rees, William A.
AU - Bennett, Jeffrey L.
AU - She, Dewei
AU - Katz, Eliezer
AU - Cree, Bruce A.C.
AU - Fujihara, Kazuo
AU - Paul, Friedemann
AU - Hartung, Hans Peter
AU - Marignier, Romain
AU - Kim, Ho Jin
AU - Weinshenker, Brian G.
AU - Pittock, Sean J.
AU - Wingerchuk, Dean M.
AU - Cutter, Gary R.
AU - Green, Ari J.
AU - Mealy, Maureen A.
AU - Drappa, Jorn
N1 - Funding Information:
The N‐MOmentum trial was funded by MedImmune and Viela Bio. Viela Bio supported the development of this manuscript, provided data analyses according to the direction of the authors, and paid for editorial assistance and clerical support. Dr Ian M. Williams of Oxford PharmaGenesis Ltd, supported the development of the project by providing administrative and editorial assistance, according to the direction of the authors. The final approval of content, drafting and revising of the manuscript, and decision to submit this manuscript rested with the authors.
Publisher Copyright:
© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2021/5
Y1 - 2021/5
N2 - Objective: Blood tests to monitor disease activity, attack severity, or treatment impact in neuromyelitis optica spectrum disorder (NMOSD) have not been developed. This study investigated the relationship between serum glial fibrillary acidic protein (sGFAP) concentration and NMOSD activity and assessed the impact of inebilizumab treatment. Methods: N-MOmentum was a prospective, multicenter, double-blind, placebo-controlled, randomized clinical trial in adults with NMOSD. sGFAP levels were measured by single-molecule arrays (SIMOA) in 1,260 serial and attack-related samples from 215 N-MOmentum participants (92% aquaporin 4-immunoglobulin G-seropositive) and in control samples (from healthy donors and patients with relapsing–remitting multiple sclerosis). Results: At baseline, 62 participants (29%) exhibited high sGFAP concentrations (≥170 pg/ml; ≥2 standard deviations above healthy donor mean concentration) and were more likely to experience an adjudicated attack than participants with lower baseline concentrations (hazard ratio [95% confidence interval], 3.09 [1.6–6.1], p = 0.001). Median (interquartile range [IQR]) concentrations increased within 1 week of an attack (baseline: 168.4, IQR = 128.9–449.7 pg/ml; attack: 2,160.1, IQR = 302.7–9,455.0 pg/ml, p = 0.0015) and 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 increase in sGFAP occurred primarily in placebo-treated participants (FC: 20.2, IQR = 4.4–98.3, p = 0.001) and was not observed in inebilizumab-treated participants (FC: 1.1, IQR = 0.8–24.6, p > 0.05). Five participants (28%) with elevated baseline sGFAP reported neurological symptoms leading to nonadjudicated attack assessments. Interpretation: Serum GFAP may serve as a biomarker of NMOSD activity, attack risk, and treatment effects. ANN NEUROL 2021;89:895–910.
AB - Objective: Blood tests to monitor disease activity, attack severity, or treatment impact in neuromyelitis optica spectrum disorder (NMOSD) have not been developed. This study investigated the relationship between serum glial fibrillary acidic protein (sGFAP) concentration and NMOSD activity and assessed the impact of inebilizumab treatment. Methods: N-MOmentum was a prospective, multicenter, double-blind, placebo-controlled, randomized clinical trial in adults with NMOSD. sGFAP levels were measured by single-molecule arrays (SIMOA) in 1,260 serial and attack-related samples from 215 N-MOmentum participants (92% aquaporin 4-immunoglobulin G-seropositive) and in control samples (from healthy donors and patients with relapsing–remitting multiple sclerosis). Results: At baseline, 62 participants (29%) exhibited high sGFAP concentrations (≥170 pg/ml; ≥2 standard deviations above healthy donor mean concentration) and were more likely to experience an adjudicated attack than participants with lower baseline concentrations (hazard ratio [95% confidence interval], 3.09 [1.6–6.1], p = 0.001). Median (interquartile range [IQR]) concentrations increased within 1 week of an attack (baseline: 168.4, IQR = 128.9–449.7 pg/ml; attack: 2,160.1, IQR = 302.7–9,455.0 pg/ml, p = 0.0015) and 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 increase in sGFAP occurred primarily in placebo-treated participants (FC: 20.2, IQR = 4.4–98.3, p = 0.001) and was not observed in inebilizumab-treated participants (FC: 1.1, IQR = 0.8–24.6, p > 0.05). Five participants (28%) with elevated baseline sGFAP reported neurological symptoms leading to nonadjudicated attack assessments. Interpretation: Serum GFAP may serve as a biomarker of NMOSD activity, attack risk, and treatment effects. ANN NEUROL 2021;89:895–910.
UR - http://www.scopus.com/inward/record.url?scp=85103385971&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103385971&partnerID=8YFLogxK
U2 - 10.1002/ana.26067
DO - 10.1002/ana.26067
M3 - Article
C2 - 33724534
AN - SCOPUS:85103385971
SN - 0364-5134
VL - 89
SP - 895
EP - 910
JO - Annals of Neurology
JF - Annals of Neurology
IS - 5
ER -