NDM02
Impact of Low Affinity IgG Fc Region Receptor III-a Gene Polymorphisms on Neuromyelitis Optica Spectrum Disorder Treatment Outcomes: N-Momentum Study

Thursday, June 2, 2022
Prince George's Exhibit Hall (Gaylord National Resort & Convention Center)
Orhan Aktas, MD , Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
Jeffrey L Bennett, MD, PhD , Professor of Neurology and Ophthalmology, University of Colorado, School of Medicine, Anschutz Medical Campus, Aurora, CO
Brian G Weinshenker, MD , Neurology, Mayo Clinic, Rochester, MN
Friedemann Paul, MD , Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité Universitätsmedizin Berlin, Berlin, Germany
Ho Jin Kim, MD , Neurology, Research Institute and Hospital of National Cancer Center, Seoul, Korea, Republic of (South)
Hans-Peter Hartung, MD , Heinrich-Heine University, Düsseldorf, Germany, Brain and Mind Center, University of Sydney, Sydney, NSW, Australia, Heinrich-Heine University, Düsseldorf, Germany
William B Rees, PhD , Translational Medicine, Horizon Therapeutics plc, Gaithersburg, MD
Dewei She, PhD , Biometrics, Horizon Therapeutics plc, Gaithersburg, MD
Eliezer Katz, MD, FACS , Clinical Development, Horizon Therapeutics plc, Gaithersburg, MD
Bruce A.C. Cree, MD , UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA
PDF


Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoantibody-mediated CNS disease. The rs396991 F176V polymorphism of the low-affinity IgG Fc region receptor III-A (FCGR3A) gene affects IgG binding affinity. Approximately 40% of Caucasians and African Americans are F/F homozygous dominant, which is associated with reduced efficacy of anti-CD20 therapies.

Objectives: To characterize the relationship between rs396991 polymorphism, NMOSD disease activity, and treatment response in N-MOmentum trial participants.

Methods: N-MOmentum (NCT02200770) was a double-blind, phase 2/3 trial that assessed the efficacy and safety of inebilizumab in adults with NMOSD, with a 28-week randomized controlled period (RCP); (intravenous inebilizumab 300 mg or placebo on days 1 and 15) and an open-label period (OLP) of ≥2 years. A total of 142 participants (inebilizumab, n=104; placebo, n=38) consented for genotyping via TaqMan qPCR assay.

Results: Historical annualized attack rates (AARs) and change in Expanded Disability Status Scale (EDSS) scores from NMOSD onset to enrollment were nominally higher in rs396991 V-allele carriers (V-allele genotype [V/V or V/F], n=74) than in F/F–allele homozygotes (n=68). In the placebo group, AAR, new/enlarged T2 MRI lesions, and NMOSD-related hospitalizations were nominally higher in V-allele carriers than in F/F–allele homozygotes. At the RCP end, V-allele carriers receiving inebilizumab had greater median (IQR) B-cell depletion than F/F–allele homozygotes, as well as nominally lower AAR and new/enlarged T2 lesions though these were not statistically significant. In the OLP, there was little difference between the subgroups in clinical metrics or B-cell depletion.

Conclusions: V-allele carriers may have increased NMOSD disease activity as compared to F/F-allele homozygotes. In this study of inebilizumab treated participants, no significant differences in outcomes were seen between those with F and V allele genotypes.

See more of: Neuroimmunology and Disease Models
See more of: Posters
<< Previous Abstract | Next Abstract