Inebilizumab for treatment of neuromyelitis optica spectrum disorder in patients with prior rituximab use from the N-MOmentum Study
Inebilizumab for treatment of neuromyelitis optica spectrum disorder in patients with prior rituximab use from the N-MOmentum Study
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DOI：
10.1016/j.msard.2021.103352
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发表时间：
2022-01-01
影响因子：
4
通讯作者：
Cree, Bruce A. C.
中科院分区：
文献类型：
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作者：
Flanagan, Eoin P.;Levy, Michael;Cree, Bruce A. C.
背景资料：B细胞耗竭剂利妥昔单抗（抗CD 20）历史上用于预防视神经肌萎缩症（NMOSD）的发作。Inebilizumab靶向并清除表达CD 19的B细胞、浆母细胞和一些浆细胞，根据随机、安慰剂对照、2/3期N-MO-mentum试验的结果，已获得美国食品药品监督管理局批准用于治疗NMOSD。由于它们的作用机制密切相关，因此考虑Inebilizumab是否可能是既往有利妥昔单抗治疗经验的患者的合适治疗选择非常重要。对来自N-MO-mentum的数据的事后分析评估了先前用利妥昔单抗治疗的参与者中inebilizumab的疗效和耐受性。nbsp;研究方法：在为期6个月的随机对照期和开放期内，通过先前使用利妥昔单抗来评估判定的发作、次要疗效结局和治疗后出现的不良事件。结果：17名N-MO-mentum参与者既往使用过利妥昔单抗，其中13名被随机分配到inebilizumab治疗组。尽管使用了利妥昔单抗，其中7名参与者在入组前发生了突破性发作（年化发作率，0.78次发作/人年）。当他们在随机对照期接受inebilizumab时，13名先前使用利妥昔单抗的参与者中有1人发生了发作（与所有安慰剂相比的风险比为0.16; 95%置信区间：0.02 1.20; p = 0.07）。另外两名先前使用利妥昔单抗的参与者在开放标签期间经历了inebilizumab的攻击，总体年化攻击率为0.08（95%置信区间：0.02 - 0.34）攻击/人-年。该年发病率与既往未使用利妥昔单抗的受试者相似（0.10 [95%置信区间：0.07 - 0.15]）。7名在接受利妥昔单抗治疗时发生发作的参与者中，没有一人在接受inebilizumab治疗时发生发作。两名（12%）先前使用利妥昔单抗的参与者经历了与inebilizumab相关的严重治疗后出现的不良事件，其中各有3名（18%）参与者发生严重或≥ 3级感染。该队列中没有死亡或机会性感染的报告。结论：这些发现支持inebilizumab在既往接受过利妥昔单抗治疗的NMOSD患者中的疗效。几乎所有先前暴露于利妥昔单抗的研究参与者都发生了感染，这突出表明需要对这些个体进行临床警戒。需要进一步研究以确定inebilizumab的潜在安全性问题，包括感染风险，在利妥昔单抗经验丰富的患者中。nbsp;
Background: The B-cell-depleting agent rituximab (anti-CD20) was historically used to prevent attacks in neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab, which targets and depletes CD19-expressing B cells, plasmablasts, and some plasma cells, received approval from the US Food and Drug Administration for treatment of NMOSD based on results from the randomized, placebo-controlled, phase 2/3 N-MO-mentum trial. Because of their closely related mechanisms of action, consideration as to whether inebilizumab may be a suitable treatment option for patients with prior rituximab experience is important. This post hoc analysis of data from N-MO-mentum assessed inebilizumab efficacy and tolerability in participants previously treated with rituximab.& nbsp;Methods: Adjudicated attacks, secondary efficacy outcomes, and treatment-emergent adverse events were assessed by prior rituximab use during a 6-month randomized control period and open-label period.& nbsp;Results: Seventeen participants in N-MO-mentum had prior rituximab use, of whom 13 were randomly assigned to the inebilizumab treatment group. Seven of these participants had breakthrough attacks prior to enrollment (annualized attack rate, 0.78 attacks/person-year) despite rituximab use. While they were receiving inebilizumab in the randomized control period, 1 of 13 participants with prior rituximab use had an attack (hazard ratio vs all placebo, 0.16; 95% confidence interval: 0.02 1.20; p = 0.07). Two additional participants with prior rituximab use experienced attacks on inebilizumab during the open-label period, with an overall annualized attack rate of 0.08 (95% confidence interval: 0.02 0.34) attacks/person-year. This annualized attack rate was similar to that of participants without prior rituximab use (0.10 [95% confidence interval: 0.07 0.15]). None of the 7 participants who experienced attacks while taking rituximab experienced an attack while receiving inebilizumab. Two (12%) participants with prior rituximab use experienced serious treatment-emergent adverse events related to inebilizumab, with serious or grade >= 3 infections occurring in 3 (18%) participants each. No deaths or opportunistic infections were reported in this cohort.& nbsp;Conclusions: These findings support the efficacy of inebilizumab in participants with NMOSD who had previously been treated with rituximab. Infections occurred in nearly all study participants with prior rituximab exposure, highlighting a need for clinical vigilance in such individuals. Further studies are necessary to determine potential safety concerns of inebilizumab, including risk of infection, in rituximab-experienced patients.& nbsp;