Efficacy and safety of inebilizumab in Asian participants with neuromyelitis optica spectrum disorder: Subgroup analyses of the N-MOmentum study

Background: Inebilizumab, an anti-CD19 B cell-depleting antibody, reduced the risk of a neuromyelitis optica spectrum disorder (NMOSD) attack, disability worsening, magnetic resonance imaging (MRI) lesion activity, and disease-related hospitalizations in participants with NMOSD in the N-MOmentum study (NCT02200770). However, the efficacy and safety outcomes of inebilizumab specific to an Asian population were not fully re-ported. Therefore, subgroup analyses of the N-MOmentum study were conducted post hoc to evaluate the efficacy and safety of inebilizumab in Asian participants with NMOSD.Methods: The N-MOmentum study was a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial with an open-label extension period (OLP). In the subgroup analyses, data from Asian participants from the N-MOmentum study were compared with those of non-Asian participants. Eligible participants were randomly allocated (3:1) to receive 300 mg intravenous (IV) inebilizumab or placebo on Days 1 and 15. Participants who had an NMOSD attack or completed the randomized controlled period (RCP) could enter the OLP, where they received inebilizumab for >= 2 years. All participants who entered the OLP received inebilizumab 300 mg IV every 6 months.Results: Overall, 230 participants received treatment (174 received inebilizumab and 56 received placebo), of whom 47 were Asian (39 received inebilizumab and 8 received placebo). Baseline characteristics were similar between the Asian and non-Asian subgroups, except for disease duration, annualized relapse rate prior to randomization in this study, and previous maintenance therapy. In the Asian subgroup, the risk of NMOSD at-tacks was reduced with inebilizumab versus placebo (hazard ratio, 0.202) and the attack-free rate at 28 weeks was 82.1% with inebilizumab versus 37.5% with placebo, in the 6-month RCP. NMOSD attack rates were comparable between the Asian and non-Asian subgroups. In the Asian subgroup, the rates of Expanded Disability Status Scale worsening from baseline, active MRI lesions, and disease-related hospitalizations tended to be lower in the inebilizumab group than in the placebo group; similar results were shown in the non-Asian subgroup. For long-term efficacy and safety (RCP and OLP), the annualized adjudicated NMOSD attack rate in Asian partici-pants treated with inebilizumab was reduced (0.096) compared with that at baseline (1.04), with a mean followup period of inebilizumab treatment of 3.38 years, which was consistent with the results in the non-Asian subgroup. The risk of NMOSD attack decreased with prolonged duration of treatment in both the inebilizu-mab/inebilizumab and placebo/inebilizumab groups in the Asian and non-Asian subgroups. The incidence of treatment-emergent adverse events (TEAEs) was similar between the Asian and non-Asian subgroups. In the Asian and non-Asian subgroups, 15.2% and 35.2% of participants, respectively, had at least one serious TEAE and/or Grade >= 3 TEAE during long-term therapy. No deaths occurred in the Asian subgroup whereas three deaths occurred in the non-Asian subgroup.Conclusion: Inebilizumab reduced the risk of an NMOSD attack, progression of disability, MRI lesion activity, and disease-related hospitalizations in Asian participants with NMOSD. The efficacy of inebilizumab in reducing NMOSD attacks continued without any unexpected safety signals or concerns during long-term use in Asian participants.