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

• DOI: 10.1016/j.ebiom.2022.104321
• Publication Date: 2022-11-10T05:18:17Z
• Authors: Jeffrey L. Bennett; Orhan Aktas; William A. Rees; Michael A. Smith; Michele Gunsior; Li Yan; Dewei She; Daniel Cimbora; Sean J. Pittock; Brian G. Weinshenker; Friedemann Paul; Romain Marignier; Dean Wingerchuk; Gary Cutter; Ari Green; Hans-Peter Hartung; Ho Jin Kim; Kazuo Fujihara; Michael Levy; Eliezer Katz; Bruce A.C. Cree
• Keywords: Neuromyelitis Optica; Spectrum disorder

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 longitudinal reductions NMOSD activity after inebilizumab was characterised post hoc exploratory analysis from N-MOmentum study (NCT02200770).Peripheral blood CD20+ B cells, PC gene signature, levels were assessed throughout (follow-up ≥2.5 years); correlations clinical metrics magnetic resonance imaging (MRI) lesion assessed.Inebilizumab induced durable B-cell within 1 week versus placebo. Although no association observed counts at time attack activity, depth first dosing period correlated outcomes. All participants receiving demonstrated a robust long-term therapeutic response, ≤4 cells/μL 6-month interval had persistently deeper depletion, lower annualised 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] 1.36 [1.12-1.61]; < 0.0001), trend towards decreased Expanded Disability Status Scale worsening (0.076 [0.06-0.10] 0.14 [0.10-0.18]; 0.093). Antibodies to inebilizumab, although present proportion treated participants, did not alter outcomes.This suggests that compared placebo, can provide specific, rapid, cells NMOSD. deep persistent correlates stability, early, improved disease 2 years.Horizon Therapeutics (formerly Viela Bio/MedImmune).