Rocky Mountain Multiple Sclerosis Center, Department of Neurology, University of Colorado, Aurora, Colorado.
NYU Grossman School of Medicine, Department of Neurology, New York University School of Medicine, New York City, New York.
Ann Clin Transl Neurol. 2020 Sep;7(9):1477-1487. doi: 10.1002/acn3.51136. Epub 2020 Aug 6.
Studies investigating rates and risk factors for serious safety events (SSEs) during rituximab treatment of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and related disorders are limited.
Rituximab-treated patients with MS, NMOSD, or related disorders at the Rocky Mountain and New York University MS Care Centers were included. The follow-up period was defined as the time from the initial dose of rituximab up to 12 months of last dose of rituximab or ocrelizumab (in patients who switched). Clinician-reported and laboratory data were retrospectively collected from electronic medical records.
One-thousand patients were included comprising 907 MS, 77 NMOSD, and 16 related disorders. Patients had a mean follow-up of 31.1 months and a mean cumulative rituximab dose of 4012 mg. Of the 169 patients who switched to ocrelizumab, the mean ocrelizumab dose was 1141 mg. Crude incidence rate per 1000 person-years (PY) for lymphopenia was 19.2, neutropenia 5.6, and hypogammaglobulinemia 17.8. Infections resulting in either hospitalization, IV antibiotics, or using antibiotics ≥14 days occurred at a rate of 38.6/1000 PY. Risk factors for infection were duration of therapy, male gender, increased disability, prior exposure to immunosuppression/chemotherapy, lymphopenia, and hypogammaglobulinemia. Particularly, wheelchair-bound patients had 8.56-fold increased odds of infections. Crude incidence rates of malignant cancer were 3.5, new autoimmune disease 2.3, thromboembolic event 3.1, and mortality of 5.4 per 1000 PY.
Rates of SSEs in patients with MS, NMOSD, and related disorders were low. Through properly assessing risk:benefit of B-cell depleting therapy in neuroinflammatory disorders and continual monitoring, clinicians may decrease the risk of serious infections.
研究调查了利妥昔单抗治疗多发性硬化症（MS）、视神经脊髓炎谱系障碍（NMOSD）和相关疾病时严重安全事件（SSE）的发生率和风险因素，但此类研究十分有限。
纳入了落基山和纽约大学 MS 护理中心接受利妥昔单抗治疗的 MS、NMOSD 或相关疾病患者。随访期定义为从利妥昔单抗初始剂量到最后一剂利妥昔单抗或奥瑞珠单抗（在转为奥瑞珠单抗的患者中）的 12 个月。从电子病历中回顾性收集临床医生报告和实验室数据。
共纳入 1000 例患者，包括 907 例 MS、77 例 NMOSD 和 16 例相关疾病。患者的平均随访时间为 31.1 个月，平均累积利妥昔单抗剂量为 4012mg。在 169 例转为奥瑞珠单抗的患者中，奥瑞珠单抗的平均剂量为 1141mg。淋巴细胞减少症的发生率为每 1000 人年（PY）19.2 例，中性粒细胞减少症为 5.6 例，低丙种球蛋白血症为 17.8 例。因感染而住院、静脉使用抗生素或使用抗生素≥14 天的发生率为 38.6/1000 PY。感染的危险因素包括治疗持续时间、男性、残疾加重、既往免疫抑制/化疗暴露、淋巴细胞减少症和低丙种球蛋白血症。特别是坐轮椅的患者感染的几率增加了 8.56 倍。每 1000 PY 的恶性肿瘤发生率为 3.5 例，新发自身免疫性疾病为 2.3 例，血栓栓塞事件为 3.1 例，死亡率为 5.4 例。
MS、NMOSD 和相关疾病患者的 SSE 发生率较低。通过适当评估神经炎症性疾病中 B 细胞耗竭治疗的风险获益，并持续监测，临床医生可能会降低严重感染的风险。
