Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of <scp><i>FCGR3A</i></scp> polymorphism
Ho Jin Kim, Orhan Aktaş, Kristina R. Patterson, Schaun Korff, Amy Kunchok, Jeffrey L. Bennett, Brian G. Weinshenker, Friedemann Paul, Hans‐Peter Hartung, Daniel Cimbora, Michael Smith, Nanette Mittereder, William A. Rees, Dewei She, Bruce Cree
Abstract
Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B-cells, is approved to treat aquaporin 4 (AQP4) IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III-A (FCGR3A) receptors on natural killer cells to maximize antibody-dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG-binding affinity and reduce rituximab (anti-CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab-treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.