Objectives There are limited real-life data regarding the efficacy and safety of rituximab (RTX) as a remission-maintenance agent in microscopic-polyangiitis (ΜPA) and granulomatosis-with-polyangiitis (GPA). We aimed to estimate the incidence and risk factors for relapses, as well serious-adverse-events (SAEs) in MPA/GPA patients during RTX-maintenance. Methods Retrospective cohort of newly-diagnosed/relapsing GPA/MPA patients who received RTX-maintenance (≥1 RTX-cycle, ≥6 months follow-up) following complete-remission (Birmingham-Vasculitis-Activity-Score-version-3 = 0 plus prednisolone ≤7.5 mg/day) with induction regimens. SAEs included serious-infections, COVID-19-associated hospitalizations, deaths, cardiovascular-events, malignancies and hypogammaglobulinemia. Incidence-rates (IR) and relapse-free survival through Kaplan-Meier plots were estimated. Cox-regression was conducted to investigate factors associated with the time-to-relapse. Results 101 patients were included; 48% females, 69% GPA, 53% newly diagnosed, median age: 63 years. During follow-up (294.5 patient-years, median: 3 RTX-cycles), 30 relapses (57% major) occurred among 24 patients (24%, IR 10.2/100 patient-years). Kidney involvement (adjusted-Hazard-Ratio/aHR: 0.20; 95% CI: 0.06–0.74, p= 0.016), prior induction with RTX plus cyclophosphamide (vs RTX monotherapy: aHR = 0.02; 95% CI: 0.001–0.43, p= 0.012) and shorter time-interval until complete-remission (aHR = 1.07; 95% CI: 1.01–1.14, p= 0.023) were associated with decreased relapse-risk. We recorded 17 serious-infections (IR 5.8/100 patient-years), 11 COVID-19-associated hospitalizations (IR 3.7/100 patient-years), 4 malignancies (IR 1.4/100 patient-years), 6 cardiovascular-events (IR 2/100 patient-years) and 10 deaths (IR 3.4/100 patient-years). Conclusion In this real-world study, relapses during RTX-maintenance occurred in approximately in 1 out of 4 patients. Kidney involvement, induction with RTX plus cyclophosphamide and earlier achievement of complete-remission were associated with lower relapse-risk. Serious-infections rate was consistent with previous reports, whereas an increased rate of COVID19-associated hospitalizations was observed.

中文翻译：

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ANCA 相关性血管炎利妥昔单抗维持治疗期间的复发和严重不良事件：一项多中心回顾性研究


目的 关于利妥昔单抗 (RTX) 作为缓解维持剂治疗显微镜下多血管炎 (MPA) 和肉芽肿性多血管炎 (GPA) 的有效性和安全性的现实数据有限。我们的目的是评估 MPA/GPA 患者在 RTX 维持期间复发的发生率和危险因素以及严重不良事件 (SAE)。方法 完全缓解后接受 RTX 维持治疗（≥1 个 RTX 周期，≥6 个月随访）的新诊断/复发 GPA/MPA 患者的回顾性队列（伯明翰血管炎活动评分版本 3 = 0）加泼尼松龙≤7.5 mg/天）并采用诱导方案。 SAE 包括严重感染、与 COVID-19 相关的住院治疗、死亡、心血管事件、恶性肿瘤和低丙种球蛋白血症。通过 Kaplan-Meier 图估计发病率 (IR) 和无复发生存率。进行 Cox 回归来调查与复发时间相关的因素。结果 纳入101例患者； 48% 为女性，69% GPA，53% 新诊断，中位年龄：63 岁。在随访期间（294.5 患者年，中位数：3 个 RTX 周期），24 名患者（24%，IR 10.2/100 患者年）中发生 30 次复发（57% 严重）。肾脏受累（调整后风险比/aHR：0.20；95% CI：0.06–0.74，p= 0.016），事先用 RTX 加环磷酰胺诱导（与 RTX 单药治疗相比：aHR = 0.02；95% CI：0.001–0.43，p = 0.012）和更短的完全缓解时间间隔（aHR = 1.07；95% CI：1.01–1.14，p = 0.023）与复发风险降低相关。我们记录了 17 例严重感染（IR 5.8/100 患者年）、11 例与 COVID-19 相关的住院治疗（IR 3.7/100 患者年）、4 例恶性肿瘤（IR 1.4/100 患者年）、6 例心血管事件（ IR 2/100 患者年）和 10 例死亡（IR 3.4/100 患者年）。 结论 在这项真实世界研究中，大约四分之一的患者在 RTX 维持期间出现复发。肾脏受累、RTX 加环磷酰胺诱导以及较早实现完全缓解与较低的复发风险相关。严重感染率与之前的报告一致，但观察到与新冠病毒相关的住院率有所增加。