双重滤过血浆置换联合利妥昔单抗的早期全程B细胞耗竭方案对增殖性狼疮性肾炎的短期疗效

The efficacy and safety of early whole-course B cell depletion therapy combined with double filtration plasmapheresis and Rituximab on proliferative Lupus nephritis

目的 探讨双重滤过血浆置换(DFPP)联合利妥昔单抗(RTX)的早期全程B细胞耗竭方案治疗增殖性狼疮性肾炎(LN)的短期疗效。方法 选择2019年7月—2022年6月间在复旦大学附属中山医院经肾穿刺活组织检查(简称活检)确诊为增殖性LN的64例患者,根据治疗方案分为传统药物组和早期全程B细胞耗竭组。随访时间为6个月,采集基线和随访期间临床参数、患者总体生存率和肾脏转归情况,比较两种治疗方案的安全性和有效性。结果 将符合纳排标准的48例患者纳入统计分析,其中传统药物组34例,早期全程B细胞耗竭组14例。随访1个月时,早期全程B细胞耗竭组的CD19细胞数和抗dsDNA抗体滴度显著低于传统药物组,补体C3水平显著高于传统药物组(P<0.001或<0.05);随访6个月时,早期全程B细胞耗竭组的尿红细胞计数、CD19细胞数、血肌酐水平、24 h尿蛋白定量和抗dsDNA抗体滴度均显著低于传统药物组(P<0.001或<0.05),总补体水平显著高于传统药物组(P<0.05)。生存曲线分析显示,两组间总体生存率和肾脏存活率的差异均无统计学意义(P值均<0.05)。传统药物组患者肾脏完全缓解率和部分缓解率均为41.2%(14/34)、不缓解率为17.6%(6/34),早期全程B细胞耗竭组患者肾脏完全缓解率为11/14、部分缓解率为3/14、不缓解率为0,两组患者肾脏缓解情况构成的差异具有统计学意义(P=0.044)。两组不良事件发生率的差异无统计学意义(P=0.104)。结论 与传统药物治疗相比,早期全程B细胞耗竭治疗有助于早期、迅速清除外周血中的自身抗体和免疫复合物沉积,在6个月的短期随访中显示出更好的肾脏预后,为增殖性LN的治疗提供了可行的新方案。

Objective To explore the short-term efficacy and safety of early whole-course B cell depletion therapy combined with double filtration plasmapheresis(DFPP)and Rituximab(RTX)on proliferative lupus nephritis(LN).Methods A total of 64 patients with proliferative LN confirmed by renal biopsy at Zhongshan Hospital affiliated to Fudan University from July 2019 to June 2022 were divided into traditional treatment group and early whole-course B cell depletion group,and the patients were followed up for 6 months.Clinical parameters,patient survival status and renal outcome were collected at baseline and during the follow-up period.Results A total of 48 patients were included in the analysis according to the inclusion and exclusion criteria.There were 34 cases in traditional treatment group and 14 cases in the early whole-course B cell depletion group.The CD19 absolute cell count and anti-dsDNA antibody titer at 1 month of follow-up in early whole-course B-cell depletion group were significantly lower than those in traditional treatment group(P<0.001 or P<0.05),while the complement C3 was significantly higher than that in traditional treatment group(P<0.05).At 6 months of follow-up,uRBC,CD19 absolute cell count,blood creatinine,24-hour urine protein and anti-dsDNA antibody titer in early whole-course B cell depletion group were significantly lower than that in the traditional treatment group(P<0.001 or P<0.05).Survival curve analysis demonstrated no statistical difference in overall survival rate or renal survival rate between the two groups(both P<0.05).In terms of renal response,the complete and partial renal remission rates of patients in the traditional treatment group were both 41.2%(14/34),and the non-remission renal rate was 17.6%(6/34);while the complete and partial renal remission rates of patients in B cell depletion group were respectively 11/14 and 3/14,and the non-remission renal remission rate was 0,indicating a significant difference between the two groups(P=0.044).Conclusion Early whole-course B cell depletion therapy has a better renal response during a short-term follow-up of 6 months,which may quickly eliminate peripheral antibodies and provide an alternative treatment of proliferative LN.