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| Item Type: | Article |
|---|---|
| Title: | Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: An exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial |
| Creators Name: | Bennett, J.L., Aktas, O., Rees, W.A., Smith, M.A., Gunsior, M., Yan, L., She, D., Cimbora, D., Pittock, S.J., Weinshenker, B.G., Paul, F., Marignier, R., Wingerchuk, D., Cutter, G., Green, A., Hartung, H.P., Kim, H.J., Fujihara, K., Levy, M., Katz, E. and Cree, B.A.C. |
| Abstract: | BACKGROUND: Inebilizumab is an anti-CD19 antibody approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with aquaporin-4 autoantibodies. The relationship between B-cell, plasma-cell (PC), and immunoglobulin depletion with longitudinal reductions in NMOSD activity after inebilizumab treatment was characterised post hoc in an exploratory analysis from the N-MOmentum study (NCT02200770). METHODS: Peripheral blood CD20+ B cells, PC gene signature, and immunoglobulin levels were assessed throughout N-MOmentum (follow-up =2.5 years); correlations with clinical metrics and magnetic resonance imaging (MRI) lesion activity were assessed. FINDINGS: Inebilizumab induced durable B-cell and PC depletion within 1 week versus placebo. Although no association was observed between B-cell counts at time of attack and NMOSD activity, depth of B-cell depletion after the first dosing period correlated with clinical outcomes. All participants receiving inebilizumab demonstrated a robust long-term therapeutic response, and participants with =4 cells/µL after the first 6-month dosing interval had persistently deeper B-cell depletion, lower annualised attack rates (estimated rate [95% CI]: 0.034 [0.024–0.04] vs 0.086 [0.056–0.12]; p = 0.045), fewer new/enlarging T2 MRI lesions (0.49 [0.43–0.56] vs 1.36 [1.12–1.61]; p < 0.0001), and a trend towards decreased Expanded Disability Status Scale worsening (0.076 [0.06–0.10] vs 0.14 [0.10–0.18]; p = 0.093). Antibodies to inebilizumab, although present in a proportion of treated participants, did not alter outcomes. INTERPRETATION: This analysis suggests that compared with placebo, inebilizumab can provide specific, rapid, and durable depletion of B cells in participants with NMOSD. Although deep and persistent CD20+ B-cell depletion correlates with long-term clinical stability, early, deep B-cell depletion correlates with improved disease activity metrics in the first 2 years. |
| Keywords: | Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, Devic Disease, Anti-CD19 Monoclonal Antibody, B-Cell Suppression |
| Source: | EBioMedicine |
| ISSN: | 2352-3964 |
| Publisher: | Elsevier |
| Volume: | 86 |
| Page Range: | 104321 |
| Date: | December 2022 |
| Official Publication: | https://doi.org/10.1016/j.ebiom.2022.104321 |
| PubMed: | View item in PubMed |
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