Astrocytic and Axonal Injury Biomarkers in AQP4 Antibody-Positive NMOSD: Insights From PREVENT and CHAMPION-NMOSD.
12 affiliations
- 1Neurology, Mayo Clinic, Phoenix, AZ.
- 2Neurology, University of Colorado, Aurora, CO.
- 3Neurology, Technical University of Munich, Germany.
- 4Neurology, University of Utah Health, Salt Lake City.
- 5Neurology, National Cancer Center, Goyang, Republic of Korea.
- 6Neurology, Keio University School of Medicine, Tokyo, Japan.
- 7Neurology, CHU de Strasbourg, France.
- 8Neurology, The University of Osaka Graduate School of Medicine, Japan.
- 9NHO Osaka Toneyama Medical Center, Toyonaka, Japan.
- 10Acumetis, Toronto, ON, Canada.
- 11Alexion, AstraZeneca Rare Disease, Boston, MA; and.
- 12Alexion, AstraZeneca Rare Disease, Rochester, MN.
Abstract
Background and objectives
Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are biomarkers of astrocytic and axonal injury, respectively, in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-Ab+ NMOSD). We evaluated serum GFAP and NfL levels during treatment with complement component 5 inhibitors eculizumab or ravulizumab and examined associations between pretreatment biomarker levels, clinical characteristics, and on-trial relapse risk using samples from the PREVENT (eculizumab) and CHAMPION-NMOSD (ravulizumab) phase 3 trials.Methods
Serum GFAP and NfL levels were analyzed retrospectively in PREVENT and prospectively in CHAMPION-NMOSD and compared with levels in demographically matched external healthy donors. Associations between baseline clinical characteristics and high biomarker levels (≥2 SDs above the healthy donor mean) were evaluated using logistic regression with a test-and-validate strategy. Changes throughout treatment were assessed relative to pretreatment baseline. Biomarker changes associated with adjudicated on-trial relapses were examined. Associations between baseline biomarker levels and time to first adjudicated on-trial relapse were assessed using Kaplan-Meier analyses.Results
Samples were available from 41 PREVENT and 55 CHAMPION-NMOSD patients. Pretreatment baseline GFAP and NfL levels were elevated in patients compared with healthy donors. High baseline GFAP levels were associated with older age at initial presentation, less time since last relapse, and higher baseline Hauser Ambulation Index (HAI) score. High baseline NfL levels were associated with older age and higher baseline HAI score. High baseline GFAP and NfL levels using age-adjusted Z-scores were evaluated and would not have materially changed the conclusions. The median GFAP levels declined rapidly (within 4-6 weeks) and were sustained with both eculizumab and ravulizumab. The median NfL levels declined significantly with ravulizumab but not eculizumab. In PREVENT, adjudicated on-trial relapses were associated with increased GFAP levels in placebo-treated patients, while GFAP increases were attenuated in eculizumab-treated patients.Discussion
Serum GFAP and NfL levels are elevated in patients with NMOSD and are associated with clinical features of disability. Complement component 5 blockade biologically suppresses astrocytic injury in NMOSD, validating GFAP as a pharmacodynamic biomarker and mechanistic readout of target engagement in randomized phase 3 trials. This aligns with earlier findings across different compounds in separate phase 3 trials.
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BibTeX
@article{wingerchuk2026astrocytic,
title = {{Astrocytic and Axonal Injury Biomarkers in AQP4 Antibody-Positive NMOSD: Insights From PREVENT and CHAMPION-NMOSD.}},
author = {Dean M Wingerchuk and Jeffrey L Bennett and Achim Berthele and Stacey L Clardy and Ho Jin Kim and Jin Nakahara and Jérôme de Sèze and Makoto Kinoshita and Breni Sharma and Cassandra L Uchida and Ruba Deeb Bou-Chahine and Becky Parks and Kerstin Allen and Jeannette N Stankowski and Sean J Pittock},
journal = {Neurology(R) neuroimmunology \& neuroinflammation},
year = {2026},
month = oct,
doi = {10.1212/nxi.0000000000200661},
url = {https://europepmc.org/article/MED/42848984},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Astrocytic and Axonal Injury Biomarkers in AQP4 Antibody-Positive NMOSD: Insights From PREVENT and CHAMPION-NMOSD.
AU - Dean M Wingerchuk
AU - Jeffrey L Bennett
AU - Achim Berthele
AU - Stacey L Clardy
AU - Ho Jin Kim
AU - Jin Nakahara
AU - Jérôme de Sèze
AU - Makoto Kinoshita
AU - Breni Sharma
AU - Cassandra L Uchida
AU - Ruba Deeb Bou-Chahine
AU - Becky Parks
AU - Kerstin Allen
AU - Jeannette N Stankowski
AU - Sean J Pittock
PY - 2026
DA - 2026/10/08
JO - Neurology(R) neuroimmunology & neuroinflammation
DO - 10.1212/nxi.0000000000200661
UR - https://europepmc.org/article/MED/42848984
AB - Background and objectives Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are biomarkers of astrocytic and axonal injury, respectively, in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-Ab+ NMOSD). We evaluated serum GFAP and NfL levels during treatment with complement component 5 inhibitors eculizumab or ravulizumab and examined associations between pretreatment biomarker levels, clinical characteristics, and on-trial relapse risk using samples from the PREVENT (eculizumab) and CHAMPION-NMOSD (ravulizumab) phase 3 trials.Methods Serum GFAP and NfL levels were analyzed retrospectively in PREVENT and prospectively in CHAMPION-NMOSD and compared with levels in demographically matched external healthy donors. Associations between baseline clinical characteristics and high biomarker levels (≥2 SDs above the healthy donor mean) were evaluated using logistic regression with a test-and-validate strategy. Changes throughout treatment were assessed relative to pretreatment baseline. Biomarker changes associated with adjudicated on-trial relapses were examined. Associations between baseline biomarker levels and time to first adjudicated on-trial relapse were assessed using Kaplan-Meier analyses.Results Samples were available from 41 PREVENT and 55 CHAMPION-NMOSD patients. Pretreatment baseline GFAP and NfL levels were elevated in patients compared with healthy donors. High baseline GFAP levels were associated with older age at initial presentation, less time since last relapse, and higher baseline Hauser Ambulation Index (HAI) score. High baseline NfL levels were associated with older age and higher baseline HAI score. High baseline GFAP and NfL levels using age-adjusted Z-scores were evaluated and would not have materially changed the conclusions. The median GFAP levels declined rapidly (within 4-6 weeks) and were sustained with both eculizumab and ravulizumab. The median NfL levels declined significantly with ravulizumab but not eculizumab. In PREVENT, adjudicated on-trial relapses were associated with increased GFAP levels in placebo-treated patients, while GFAP increases were attenuated in eculizumab-treated patients.Discussion Serum GFAP and NfL levels are elevated in patients with NMOSD and are associated with clinical features of disability. Complement component 5 blockade biologically suppresses astrocytic injury in NMOSD, validating GFAP as a pharmacodynamic biomarker and mechanistic readout of target engagement in randomized phase 3 trials. This aligns with earlier findings across different compounds in separate phase 3 trials.
SN - 2332-7812
ER -