利妥昔单抗在抗中性粒细胞胞质抗体相关血管炎维持治疗中的疗效研究  

Efficacy of rituximab in maintenance therapy for antineutrophil cytoplasmic antibody-associated vas-culitis

作　　者：张桂芝 谢枝隽 何石萍 白炜 杨云娇 李菁 田新平 Zhang Guizhi;Xie Zhijuan;He Shiping;Bai Wei;Yang Yunjiao;Li Jing;Tian Xinping(Department of Rheumatology and Clinical Immunology,Chinese Academy of Medical Sciences&Peking Union Medical College,National Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID),Ministry of Science&Technology,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital(PUMCH),Key Laboratory of Rheumatology and Clinical Immunology,Ministry of Education,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院风湿免疫科,国家皮肤与免疫疾病临床医学研究中心(NCRC-DID),疑难重症及罕见病国家重点实验室,风湿免疫病学教育部重点实验室,北京100730

出　　处：《中华风湿病学杂志》2022年第7期439-444,I0003,共7页Chinese Journal of Rheumatology

基　　金：中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-005)。

摘　　要：目的:分析利妥昔单抗(RTX)在难治性或复发性ANCA相关血管炎(AAV)患者维持治疗中的疗效和安全性。方法:纳入北京协和医院2005年9月至2021年6月间难治或复发性肉芽肿性多血管炎(GPA)或显微镜下多血管炎(MPA)接受RTX诱导序贯维持治疗的患者。收集患者基线和随访临床资料,对疾病复发率、复发时间和安全性数据进行分析。采用Kaplan-Meier曲线计算累积复发率、比较组间无复发生存率, t检验、Man-Whithey U检验、Fisher精确检验用于组间差异性比较。 结果:①研究纳入39例难治或复发性AAV患者,其中GPA 36例,MPA 3例,中位随访时间20(3,104)个月,59.0%(23/39)患者病情复发,复发中位时间11(3,42)个月。②标准剂量和减量诱导治疗两组复发率[60.0%(18/30)和55.6%(5/9), χ^(2)=0.06, P=1.000]、首次复发时间[15(3,42)个月和10(9,30)个月, Z=0.45, P=0.678]、CD19 + B细胞[23.5(5,148)个/μl和3(2,15)个/μl, Z=0.57, P=0.605]、血清免疫球蛋白(Ig)G水平[7.09(5.13,13.90) g/L和9.72(5.32,12.0) g/L, Z=0.36, P=0.770]差异均无统计学意义;标准剂量诱导治疗组无重症复发生存率显著高于减量诱导治疗组{87.1%[95% CI(73.4%,100.8%)和64.3%[95% CI(23.1%,105.4%)], χ^(2)=7.59, P=0.006}。③固定间隔给药组与按需给药组疾病复发率[50.0%(3/6)和60.6%(20/33), χ^(2)=0.24, P=0.674]、首次复发时间[23(6,25)个月和11(3,42)个月, Z=0.05, P=0.982]、CD19 + B细胞[35(15,50)个/μl和10(0,148)个/μl, Z=0.95, P=0.382]、血清IgG水平[6.70(5.91,7.49) g/L和7.69(3.78,13.90) g/L, Z=0.48, P=0.700]差异均无统计学意义;2组无重症复发生存率差异无统计学意义(100%和77.8%, χ^(2)=1.79, P=0.181)。④随访期间输液反应发生率为5.1%(2/39),感染率20.5%(8/39),感染时中位IgG 4.37(3.78,13.4) g/L;标准剂量和减量诱导治疗组、固定间隔给药和按需给药组感染率、感染时血清IgG水平差异均无统计学意义( P>0.05)。 结论:RTX标准剂量诱导治疗与减量诱导治Objective To evaluate the efficacy and safety of rituximab(RTX)as remission-mainten-ance therapy in antineutrophil cytoplasmic antibody(ANCA)associated vasculitis(AAV).Methods Patients with AAV,including granulomatosis with polyangiitis(GPA)and microscopic polyangiitis(MPA),treated with rituximab(RTX)in Peking Union Medical College Hospital during September 2005 to June 2021 were included into this study.Clinical data,relapse rate,time of first relapse and adverse events were collected and analyzed.The cumulative relapse rate was calculated by Kaplan-Meier,t test,and Man-Whithey U test and chi-square were used to compare differences between two groups.Results①Thirty-nine AAV patients were enrolled,including 36 GPA and 3 MPA.During the 20(3,104)months follow-up,59.0%(23/39)patients had suffered relapses.The time for first relapse was 11(3,42)months after remission.②There were no difference in the relapse rate[60.0%(18/30)vs 55.6%(5/9),χ^(2)=0.06,P=1.000),the time of first relapse[15(3,42)vs 10(9,30),Z=0.45,P=0.678],CD19+B[23.5(5,148)cell/μl vs 3(2,15)cell/μl,Z=0.57,P=0.605]and serum IgG[7.09(5.13,13.90)g/L vs 9.72(5.32,12.0)g/L,Z=0.36,P=0.770]between standard dose and low-dose groups.The rate of major relapse-free was significantly less in patients treated with standard dose than patients with reduced dose of RTX{87.1%[95%CI(73.4%,100.8R%)]vs 64.3%[95%CI(23.1%,105.4%)],χ^(2)=7.59,P=0.006}.③There were no difference in relapse rate[50.0%(3/6)vs 60.6%(20/33),χ^(2)=0.24,P=0.674],time of first relapse[23(6,25)vs 11(3,42),Z=0.05,P=0.982],CD19+B[35(15,50)cell/μl vs 10(0,148)cell/μl,Z=0.95,P=0.382]and serum IgG[6.70(5.91,7.49)g/L vs 7.69(3.78,13.90)g/L,Z=0.48,P=0.700]between the fixed interval dosage and the on-demand dosage groups.There was no difference in the rate of major relapse-free between the two groups(100%vs 77.8%,χ^(2)=1.79,P=0.181).④The incidence of infusion reaction was 5.1%(2/39)and infection was 20.5%(8/39).Serum IgG level was 4.37(3.78,13.4)g/L at infection.There was no difference in safety

关 键 词：抗中性粒细胞胞浆抗体相关性血管炎 显微镜下多血管炎 变应性肉芽肿性血管炎 复发 利妥昔单抗 

分 类 号：R969[医药卫生—药理学]