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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

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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. and Aktas, O. and Rees, W.A. and Smith, M.A. and Gunsior, M. and Yan, L. and She, D. and Cimbora, D. and Pittock, S.J. and Weinshenker, B.G. and Paul, F. and Marignier, R. and Wingerchuk, D. and Cutter, G. and Green, A. and Hartung, H.P. and Kim, H.J. and Fujihara, K. and Levy, M. and 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:http://doi.org/10.1016/j.ebiom.2022.104321
PubMed:View item in PubMed

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