Serum neurofilament light chain levels at attack predict post-attack disability worsening and are mitigated by inebilizumab: analysis of four potential biomarkers in neuromyelitis optica spectrum disorder

ObjectiveTo investigate relationships between serum neurofilament light chain (sNfL), ubiquitin C-terminal hydrolase L1 (sUCHL1), tau (sTau) and glial fibrillary acidic protein (sGFAP) levels and disease activity/disability in neuromyelitis optica spectrum disorder (NMOSD), and the effects of inebil...

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Published in:Journal of Neurology, Neurosurgery & Psychiatry Vol. 94; no. 9; pp. 757 - 768
Main Authors: Aktas, Orhan, Hartung, Hans-Peter, Smith, Michael A, Rees, William A, Fujihara, Kazuo, Paul, Friedemann, Marignier, Romain, Bennett, Jeffrey L, Kim, Ho Jin, Weinshenker, Brian G, Pittock, Sean J, Wingerchuk, Dean M, Cutter, Gary, She, Dewei, Gunsior, Michele, Cimbora, Daniel, Katz, Eliezer, Cree, Bruce A
Format: Journal Article
Language:English
Published: England BMJ Publishing Group Ltd 01.09.2023
BMJ
BMJ Publishing Group LTD
BMJ Publishing Group
Series:Original research
Subjects:
Alzheimer's disease
Antibodies, Monoclonal, Humanized - therapeutic use
Aquaporin 4
Autoantibodies
Biomarkers
CLINICAL NEUROLOGY
Double-Blind Method
Function and Dysfunction of the Nervous System
General Neurology
Humans
Immunoglobulin G
Integrative Biomedicine [Topic 3]
Intermediate Filaments
Mann-Whitney U test
Monoclonal antibodies
Neurology
Neuromyelitis Optica
Neuromyelitis Optica - blood
Neuromyelitis Optica - drug therapy
Proteins
RANDOMISED TRIALS
Statistical significance
United States > US
San Francisco California
California
RANDOMISED TRIALS
CLINICAL NEUROLOGY
ISSN:0022-3050, 1468-330X, 1468-330X
Online Access:Get full text
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Summary:ObjectiveTo investigate relationships between serum neurofilament light chain (sNfL), ubiquitin C-terminal hydrolase L1 (sUCHL1), tau (sTau) and glial fibrillary acidic protein (sGFAP) levels and disease activity/disability in neuromyelitis optica spectrum disorder (NMOSD), and the effects of inebilizumab on these biomarkers in N-MOmentum.MethodsN-MOmentum randomised participants to receive inebilizumab or placebo with a randomised controlled period (RCP) of 28 weeks and an open-label follow-up period of ≥2 years. The sNfL, sUCHL1, sTau and sGFAP were measured using single-molecule arrays in 1260 scheduled and attack-related samples from N-MOmentum participants (immunoglobulin G (IgG) autoantibodies to aquaporin-4-positive, myelin oligodendrocyte glycoprotein-IgG-positive or double autoantibody-negative) and two control groups (healthy donors and patients with relapsing–remitting multiple sclerosis).ResultsThe concentration of all four biomarkers increased during NMOSD attacks. At attack, sNfL had the strongest correlation with disability worsening during attacks (Spearman R2=0.40; p=0.01) and prediction of disability worsening after attacks (sNfL cut-off 32 pg/mL; area under the curve 0.71 (95% CI 0.51 to 0.89); p=0.02), but only sGFAP predicted upcoming attacks. At RCP end, fewer inebilizumab-treated than placebo-treated participants had sNfL>16 pg/mL (22% vs 45%; OR 0.36 (95% CI 0.17 to 0.76); p=0.004).ConclusionsCompared with sGFAP, sTau and sUCHL1, sNfL at attack was the strongest predictor of disability worsening at attack and follow-up, suggesting a role for identifying participants with NMOSD at risk of limited post-relapse recovery. Treatment with inebilizumab was associated with lower levels of sGFAP and sNfL than placebo.Trial registration number NCT02200770.
Bibliography:Original research
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SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0022-3050
1468-330X
1468-330X
DOI:10.1136/jnnp-2022-330412