CMSC 2022 | Efficacy of inebilizumab in patients with NMOSD with Fc receptor III-A polymorphisms

Bruce Cree, MD, PhD, MAS, University of California San Francisco, San Francisco, CA, summarizes an analysis of the Phase III N-MOmentum Trial (NCT02200770), assessing the relationship between IgG Fc region receptor III-A (FcγR IIIA) gene polymorphisms, disease activity, and treatment response in patients with neuromyelitis optica spectrum disorder (NMOSD). The study focused on inebilizumab, a monoclonal antibody targeting CD19+ B-cells, glycoengineered for strong binding to the FcγR IIIA. In this analysis, it was examined if inebilizumab would deplete B-cells regardless of FcγR IIIA polymorphisms, with reference to two populations: F/F allele participants (associated with decreased efficacy of rituximab) and V allele particiapnts (V; V/V or V/F genotype; associated with improved antibody FcγR binding). Interestingly, the study found that V allele patients in the placebo arm had increased overall disease activity, including higher propensity for attacks, hospitalization, disability, and lesion formation. Additionally, the study showed that during inebilizumab treatment, the V allele resulted in greater B-cell depletion within the first six months; however, after six months there was no significant difference between the responses of the two genotypes. This demonstrated that inebilizumab was effective regardless of genotype, an important improvement from rituximab to treat patients with FcγR polymorphisms. This interview took place at the Consortium of Multiple Sclerosis Centers (CMSC) congress 2022 in Maryland.