Inebilizumab (Uplizna®) treatment can provide specific, rapid, and durable CD19+ B-cell depletion in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to placebo, according to a new study published in the journal eBioMedicine: Part of The Lancet Discovery Science

Jeffrey L. Bennett, of the University of Colorado School of Medicine Anschutz Medical Campus in Aurora, and colleagues analyzed CD20+ B cells, the gene signature of plasma cells, and the levels of immunoglobulin in peripheral blood throughout the N-MOmentum study. The trial was a pivotal phase 2/3 randomized, placebo-controlled study of inebilizumab in patients with NMOSD. They assessed the correlation between clinical metrics and lesion activity for a minimum of 2.5 years of follow-up.

They found that inebilizumab treatment induced durable B-cell and plasma cell depletion within 1 week compared to placebo.


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There was no association between B-cell counts at the time of attack and disease activity. However, the depth of B-cell depletion after the first dosing period correlated with clinical outcomes. 

All patients who were treated with inebilizumab showed a robust long-term therapeutic response. Those who had 4 cells/μL or less after the first 6-month dosing interval had persistently deeper B-cell depletion, lower annualized attack rates, fewer new/enlarging T2 MRI lesions, and a trend towards decreased disability worsening. Antibodies to inebilizumab were detected in some patients. However, they did not have an effect on outcomes.

These findings support the idea that B-cell levels should be monitored in patients with NMOSD treated with inebilizumab, the authors concluded. “It remains to be investigated whether patients showing partial depletion and/or early reconstitution of B cells may achieve deeper or more sustained B-cell depletion with dose adjustments or more frequent administration,” they wrote.

Reference

Bennett J, Aktas O, Rees W, et al. 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. EBioMedicine. Published online November 9, 2022. doi:10.1016/j.ebiom.2022.104321