Departments of Neurology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Mult Scler Relat Disord. 2022 Jan;57:103352. doi: 10.1016/j.msard.2021.103352. Epub 2021 Oct 26.
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-MOmentum 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-MOmentum assessed inebilizumab efficacy and tolerability in participants previously treated with rituximab.
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.
Seventeen participants in N-MOmentum 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.
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. ClinicalTrials.gov identifier: NCT02200770.
B 细胞耗竭剂利妥昔单抗（抗 CD20）曾被用于预防视神经脊髓炎谱系疾病（NMOSD）的发作。伊奈利珠单抗靶向并耗竭表达 CD19 的 B 细胞、浆母细胞和一些浆细胞，基于随机、安慰剂对照、2/3 期 N-MOmentum 试验的结果，该药已获得美国食品和药物管理局批准用于治疗 NMOSD。由于它们的作用机制密切相关，因此需要考虑伊奈利珠单抗是否可能成为具有既往利妥昔单抗治疗经验的患者的合适治疗选择。本项 N-MOmentum 研究的事后分析评估了伊奈利珠单抗在既往接受过利妥昔单抗治疗的参与者中的疗效和耐受性。
在随机对照期和开放标签期，根据既往使用利妥昔单抗的情况，评估了有定论的发作、次要疗效终点和治疗中出现的不良事件。
N-MOmentum 中有 17 名参与者曾使用过利妥昔单抗，其中 13 名被随机分配至伊奈利珠单抗治疗组。这 13 名参与者中有 7 名在入组前发生了突破性发作（年发作率为 0.78 次/人年），尽管他们使用了利妥昔单抗。在随机对照期，13 名既往使用过利妥昔单抗的参与者中有 1 名发生了发作（与所有安慰剂相比，危险比为 0.16；95%置信区间：0.02，1.20；p=0.07）。另外 2 名既往使用过利妥昔单抗的参与者在接受伊奈利珠单抗治疗期间发生了发作，总年发作率为 0.08（95%置信区间：0.02，0.34）次/人年。该年发作率与既往未使用利妥昔单抗的参与者相似（0.10，95%置信区间：0.07，0.15）。在接受利妥昔单抗治疗时发生发作的 7 名参与者中，没有 1 名在接受伊奈利珠单抗治疗时发生发作。既往使用过利妥昔单抗的 2 名（12%）参与者发生了与伊奈利珠单抗相关的严重治疗中出现的不良事件，各有 3 名（18%）参与者出现严重或 3 级及以上感染。该队列中未报告死亡或机会性感染。
这些发现支持伊奈利珠单抗在既往接受过利妥昔单抗治疗的 NMOSD 患者中的疗效。在既往接受过利妥昔单抗暴露的几乎所有研究参与者中都发生了感染，这突出了在这些患者中需要进行临床监测。还需要进一步的研究来确定伊奈利珠单抗在利妥昔单抗治疗过的患者中的潜在安全性问题，包括感染风险。临床试验注册号：NCT02200770。
