目的:关于利妥昔单抗(RTX)作为显微镜下多血管炎(MPA)和肉芽肿性多血管炎(GPA)的缓解维持剂的疗效和安全性的实际数据有限。我们的目的是估计复发的发生率和危险因素,以及RTX维持期间MPA/GPA患者的严重不良事件(SAE)。
方法:接受RTX维持(≥1个RTX周期,≥6个月随访)完全缓解(伯明翰-血管炎-活动评分-版本3=0加泼尼松龙≤7.5mg/天),并采用诱导方案。SAE包括严重感染,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图估计发病率(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。
结果:包括101例患者;48%的女性,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例患者(24%,IR10.2/100患者年)。肾脏受累(校正风险比/aHR:0.20;95%CI:0.06-0.74,p=0.016),之前使用RTX+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)和更短的直至完全缓解的时间间隔(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(IR5.8/100患者年),11COVID-19相关住院(IR3.7/100患者年),4种恶性肿瘤(IR1.4/100患者-年),6例心血管事件(IR2/100患者年)和10例死亡(IR3.4/100患者年)。
结论:在这项现实世界的研究中,RTX维持期间的复发大约发生在4例患者中的1例。肾脏受累,RTX+环磷酰胺诱导和早期完全缓解与较低的复发风险相关.严重感染率与以前的报告一致,而观察到COVID19相关住院率增加.
OBJECTIVE: 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).
CONCLUSIONS: 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.