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

Aktas, O.; Hartung, H.P.; Smith, M.A.; Rees, W.A.; Fujihara, K.; Paul, F.; Marignier, R.; Bennett, J.L.; Kim, H.J.; Weinshenker, B.G.; Pittock, S.J.; Wingerchuk, D.M.; Cutter, G.; She, D.; Gunsior, M.; Cimbora, D.; Katz, E.; Cree, B.A.

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

Tools

Preview	PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader 3MB
	Other (Supplementary Data) 10MB

Item Type:	Article
Title:	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
Creators Name:	Aktas, O., Hartung, H.P., Smith, M.A., Rees, W.A., Fujihara, K., Paul, F., Marignier, R., Bennett, J.L., Kim, H.J., Weinshenker, B.G., Pittock, S.J., Wingerchuk, D.M., Cutter, G., She, D., Gunsior, M., Cimbora, D., Katz, E. and Cree, B.A.
Abstract:	OBJECTIVE: To 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. METHODS: N-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). RESULTS: The concentration of all four biomarkers increased during NMOSD attacks. At attack, sNfL had the strongest correlation with disability worsening during attacks (Spearman R(2)=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). CONCLUSIONS: Compared 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.
Keywords:	Aquaporin 4, Autoantibodies, Biomarkers, Immunoglobulin G, Intermediate Filaments, Neuromyelitis Optica
Source:	Journal of Neurology Neurosurgery and Psychiatry
ISSN:	0022-3050
Publisher:	BMJ Publishing Group
Volume:	94
Number:	9
Page Range:	757-768
Date:	September 2023
Official Publication:	https://doi.org/10.1136/jnnp-2022-330412
PubMed:	View item in PubMed

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year