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| 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 |
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