Recently published in Multiple Sclerosis and Related Disorders, a subgroup analysis on the phase 2/3 N-MOmentum study (NCT02200770) assessing inebilizumab (Uplizna, Horizon Therapeutics), an FDA-approved therapy for neuromyelitis optica spectrum disorder (NMOSD), highlighted the therapy’s efficacy and safety in Asian patients with the disease.1 Overall, the findings suggest inebilizumab was equally effective in both Asian and nonAsian patients in reducing risk of an attack, progression of disability, MRI lesion activity, and disease-related hospitalizations.
Among 47 patients in the Asian subgroup, the risk of NMOSD attacks was reduced with inebilizumab (n = 39) compared with placebo (n = 8) (HR, 0.202). At 28 weeks, 82.1% of patients treated with inebilizumab during the double-blind controlled period were attack-free in comparison with 37.5% for the placebo group. NMOSD attack rates were comparable between the Asian and nonAsian 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 nonAsian subgroup.
Clinical Takeaways
- Subgroup analysis indicates that inebilizumab shows superiority over placebo in reducing NMOSD attacks among Asian patients with NMOSD.
- The findings suggest that inebilizumab is equally effective in both Asian and nonAsian patients, reducing the risk of attacks, disability progression, MRI lesion activity, and disease-related hospitalizations in both subgroups.
- The study emphasizes the long-term safety of inebilizumab in both Asian and nonAsian subgroups, with no unexpected safety signals during extended use, supporting its viability as a treatment option.
“In this subgroup analysis, the risk of NMOSD attack decreased with prolonged duration of treatment in both the inebilizumab and placebo groups in the Asian subgroup, and this was also observed in the nonAsian subgroup. These findings suggest that treatment with inebilizumab monotherapy provided a continuous reduction in NMOSD attacks in the Asian and nonAsian subgroups,” lead author Kazuo Fujihara, MD, professor of multiple sclerosis therapeutics at Fukushima Medical University School of Medicine, and director of the Multiple Sclerosis & Neuromyelitis Optica Center at Southern TOHOKU Research Institute for Neuroscience (STRINS), in Koriyama, Japan, and colleagues wrote.1
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The N-MOmentum study, a phase 3 study that led to inebilizumab’s approval, was a multicenter, double-blind, randomized, placebo-controlled trial with open-label extension period (OLP).2 The eligible participants were randomized (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 RCP could then enter the OLP and all who did (n = 230) received inebilizumab (n = 174) 300 mg IV or placebo (n = 56) every 6 months for at least 2 years. In this analysis, authors noted that baseline characteristics were similar between the Asian and nonAsian subgroups, except for disease duration, annualized relapse rate (ARR) prior to randomization in this study, and previous maintenance therapy.
“The attack rate during the first 6 months was numerically higher in the placebo group in the Asian subgroup than in the placebo group in the nonAsian subgroup. This difference may be related to differences in baseline characteristics, such as ARR prior to randomization in this study and previous maintenance therapy between the Asian and nonAsian subgroups; however, it cannot be clearly concluded that there was a difference in attack rate between these groups of Asian and nonAsian subgroups owing to the small number of participants, especially in the Asian subgroup,” Fujihara et al noted.1
As observed for long-term efficacy and safety, the annualized adjudicated NMOSD attack rate was reduced (0.096) in Asian participants treated with inebilizumab compared with what was observed at baseline (1.04). In this Asian patient sample, the mean follow-up period of inebilizumab treatment was 3.38 years, which authors noted was consistent with the results in the nonAsian subgroup. Notably, the risk of NMOSD attack decreased with prolonged duration of treatment in both the inebilizumab and placebo groups in the Asian and nonAsian subgroups.
“The types and frequencies of treatment-emergent adverse events (TEAEs) were broadly similar in both the inebilizumab and placebo groups during the RCP in the Asian subgroup. The long-term safety of inebilizumab was also assessed in the OLP. The duration of inebilizumab exposure was similar between the Asian and nonAsian subgroups, and no safety issues with long-term administration were observed in the Asian and nonAsian subgroups,” Fujihara et al noted.1 During long-term therapy in the Asian and nonAsian subgroups, 15.2% and 35.2% of participants, respectively, had at least 1 serious TEAE and/or Grade at least 3 TEAEs. The authors also reported that no deaths occurred in the Asian subgroup although 3 deaths occurred in the nonAsian subgroup.
Limitations of the analysis included the limited availability of data from anti-aquaporin-4-negative participants which, according to the investigators, meant that efficacy of inebilizumab could not be determined in this subgroup. Additionally, race such as Asian versus nonAsian was not included as a stratification factor in the N-MOmentum study, and the number of Asian participants was small. Therefore, the authors noted that the participants might not be fully representative of the NMOSD population because of the exclusion of participants with certain comorbidities and pediatric patients with NMOSD.
“These points should be considered when interpreting the outcomes between the inebilizumab group and placebo group in the Asian subgroup as this may have caused differences in some baseline characteristics between the inebilizumab group and placebo group,” Fujihara et al noted.1 “Thus, efficacy and safety of long-term treatment with inebilizumab warrants future study, including post-marketing surveillance.”
REFERENCES
1. Fujihara K, Kim HJ, Saida T, et al. Efficacy and safety of inebilizumab in Asian participants with neuromyelitis optica spectrum disorder: Subgroup analyses of the N-MOmentum study. Mult Scler Relat Disord. 2023;79:104938. doi:10.1016/j.msard.2023.104938
2. Cree BAC, Bennett JL, Kim HJ, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019;394(10206):1352-1363. doi:10.1016/S0140-6736(19)31817-3
