Gialouri Chrysoula G, Chalkia Aglaia, Koutsianas Christos, Chavatza Katerina, Argyriou Evangelia, Panagiotopoulos Alexandros, Karamanakos Anastasios, Dimouli Aikaterini, Tsalapaki Christina, Thomas Konstantinos, Orfanos Philippos, Lagiou Pagona, Katsikas George, Boki Kyriaki, Boumpas Dimitrios, Petras Dimitrios, Vassilopoulos Dimitrios
Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, General Hospital of Athens "Hippokration", Athens, Greece.
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Rheumatology (Oxford). 2025 Apr 1;64(4):1989-1998. doi: 10.1093/rheumatology/keae409.
There are limited real-life data regarding the efficacy and safety of rituximab (RTX) as a remission maintenance agent in microscopic polyangiitis (MPA) and granulomatosis-with-polyangiitis (GPA). We aimed to estimate the incidence and risk factors for relapses, as well for serious adverse events (SAEs) in MPA/GPA patients during RTX maintenance.
A retrospective cohort of newly diagnosed/relapsing GPA/MPA patients who received RTX maintenance (≥1 RTX cycle, ≥6 months follow-up) following complete remission (BVAS version-3 = 0 plus prednisolone ≤7.5 mg/day) with induction regimens. SAEs included serious infections, COronaVIrus-Disease 2019 (COVID-19)-associated hospitalizations, deaths, cardiovascular events, malignancies and hypogammaglobulinemia. The incidence rates (IRs) and relapse-free survival were estimated through Kaplan-Meier plots. Cox regression was conducted to investigate factors associated with the time-to-relapse.
A total of 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 CYC (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).
In this real-world study, relapses during RTX maintenance occurred in approximately 1 out of 4 patients. Kidney involvement, induction with RTX plus CYC, and earlier achievement of complete remission were associated with lower relapse risk. The serious infections rate was consistent with previous reports, whereas an increased rate of COVID-19-associated hospitalizations was observed.
关于利妥昔单抗（RTX）作为显微镜下多血管炎（MPA）和肉芽肿伴多血管炎（GPA）缓解维持药物的疗效和安全性，现实生活中的数据有限。我们旨在评估MPA/GPA患者在RTX维持治疗期间复发以及严重不良事件（SAE）的发生率和危险因素。
对新诊断/复发的GPA/MPA患者进行回顾性队列研究，这些患者在诱导治疗方案完全缓解（BVAS第3版=0且泼尼松龙≤7.5mg/天）后接受RTX维持治疗（≥1个RTX周期，随访≥6个月）。SAE包括严重感染、2019冠状病毒病（COVID-19）相关住院、死亡、心血管事件、恶性肿瘤和低丙种球蛋白血症。通过Kaplan-Meier曲线估计发病率（IR）和无复发生存率。进行Cox回归以研究与复发时间相关的因素。
共纳入101例患者：48%为女性，69%为GPA，53%为新诊断患者，中位年龄63岁。在随访期间（294.5患者年，中位：3个RTX周期），24例患者（24%）发生了30次复发（57%为主要复发）（IR为10.2/100患者年）。肾脏受累（调整后风险比/aHR：0.20；95置信区间：0.06-0.74，P=0.016）、先前使用RTX加环磷酰胺（CYC）诱导治疗（与RTX单药治疗相比：aHR=0.02；95%置信区间：0.001-0.43，P=0.012）以及至完全缓解的时间间隔较短（aHR=1.07；95%置信区间：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为5.8/100患者年）、11例COVID-19相关住院（IR为3.7/100患者年）、4例恶性肿瘤（IR为1.4/100患者年）、6例心血管事件（IR为2/100患者年）和10例死亡（IR为3.4/100患者年）。
在这项真实世界研究中，约四分之一的患者在RTX维持治疗期间复发。肾脏受累、使用RTX加CYC诱导治疗以及更早实现完全缓解与较低的复发风险相关。严重感染率与先前报告一致，但观察到COVID-19相关住院率有所增加。
