背景:Inebilizumab,抗CD19B细胞消耗抗体,降低视神经脊髓炎谱系障碍(NMOSD)发作的风险,残疾恶化,磁共振成像(MRI)病变活动,以及N-MOmentum研究中NMOSD参与者的疾病相关住院治疗(NCT02200770)。然而,针对亚洲人群的inebilizumab的疗效和安全性结局未得到充分报道.因此,N-MOmentum研究的亚组分析是事后进行的,目的是评估在患有NMOSD的亚洲参与者中,纳比单抗的疗效和安全性.
方法:N-MOmentum研究是一个多中心,双盲,随机化,安慰剂对照2/3期试验,开放标签延长期(OLP)。在亚组分析中,来自N-MOmentum研究的亚洲参与者的数据与非亚洲参与者的数据进行了比较.符合条件的参与者被随机分配(3:1),在第1天和第15天接受300mg静脉内(IV)奈珠单抗或安慰剂。患有NMOSD攻击或完成随机对照期(RCP)的参与者可以进入OLP,在那里他们接受了≥2年的inebilizumab。所有进入OLP的参与者每6个月接受一次300mg静脉给药。
结果:总体而言,230名参与者接受了治疗(174人接受了inebilizumab,56人接受了安慰剂),其中47人是亚洲人(39人接受了inebilizumab,8人接受了安慰剂).亚洲和非亚洲亚组的基线特征相似,除了疾病持续时间,在这项研究中,随机化前的年化复发率,和以前的维持治疗。在亚洲分组中,NMOSD发作的风险与安慰剂相比降低(风险比,0.202),第28周时的无动症率为82.1%,而安慰剂为37.5%,在6个月的RCP中。NMOSD发作率在亚洲和非亚洲亚组之间具有可比性。在亚洲分组中,扩展残疾状况量表从基线恶化的比率,活跃的MRI病变,而与疾病相关的住院率在inebilizumab组中倾向于低于安慰剂组;在非亚洲亚组中也显示了类似的结果.对于长期疗效和安全性(RCP和OLP),与基线时(1.04)相比,在接受inebilizumab治疗的亚洲参与者中,年度裁定的NMOSD发作率降低(0.096),平均随访期为3.38年,这与非亚洲亚组的结果一致。在亚洲和非亚洲亚组中,随着治疗持续时间的延长,在inebilizumab/inebilizumab和安慰剂/inebilizumab组中,NMOSD发作的风险降低。在亚洲和非亚洲亚组之间,治疗引起的不良事件(TEAE)的发生率相似。在亚洲和非亚洲分组中,15.2%和35.2%的参与者,分别,在长期治疗期间至少有一次严重的TEAE和/或≥3级的TEAE。亚洲亚组没有死亡,而非亚洲亚组有3例死亡。
结论:Inebilizumab降低了NMOSD发作的风险,残疾的进展,MRI病变活动,亚洲NMOSD参与者的疾病相关住院情况。在亚洲参与者长期使用期间,在减少NMOSD发作方面,无任何意外安全信号或担忧的情况下,inebilizumab继续有效。
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 reported. 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 attacks 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 participants treated with inebilizumab was reduced (0.096) compared with that at baseline (1.04), with a mean follow-up 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 inebilizumab/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.
CONCLUSIONS: 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.