收稿日期: 2025-05-23
网络出版日期: 2025-09-05
基金资助
河南省医学科技攻关计划项目(LHGJ20230502)
Comparison of clinical efficacy of different doses of rituximab combined with tacrolimus in the treatment of idiopathic membranous nephropathy
Received date: 2025-05-23
Online published: 2025-09-05
目的 探讨他克莫司（tacrolimus，TAC）联合不同剂量利妥昔单抗（rituximab，RTX）两种用药方案，为临床治疗方案的制定提供参考依据。 方法 回顾性分析就诊于新乡医学院第一附属医院确诊为特发性膜性肾病且应用RTX联合TAC方案患者，采用倾向性评分匹配（PSM）按照1∶1比例进行匹配分析，本研究共纳入60例患者，观察组和对照组分别纳入30例患者。观察组：第1天和第15天输注剂量为375 mg/m2，用药3个月后若循环B细胞CD19 > 5个/μL，则给予输注200 mg RTX。对照组：第1天和第15天分别给予1 000 mg，6个月时若仍未达到完全缓解则给予输注RTX 1 000 mg。随访12个月用药后两组完全缓解、部分缓解以及不良事件的发生率。 结果 （1）两组24 h蛋白尿均明显下降，对照组下降幅度明显高于观察组，用药第1、3个月两组比较差异有统计学意义（P < 0.05）；白蛋白逐渐上升，且在第1、3个月两组对比均有差异有统计学意义（P < 0.05）；抗磷脂酶A2抗体用药1个月后明显下降（P < 0.05）；用药3个月时临床总缓解率对照组为63.3%，观察组为36.7%，差异有统计学意义（P < 0.05）；12个月时对照组的总缓解率为86.7%，观察组为83.3%，差异无统计学意义（P > 0.05）。用药1个月后对照组和观察组血清免疫学完全缓解率分别为33.3%和3.3%，差异有统计学意义（P < 0.05）。（2）随访前6个月对照组的累积缓解率高于观察组，观察组缓解率在6个月后明显上升，Log-rank检验显示，两组生存曲线差异无统计学意义（P = 0.37）。（3）基于多因素COX回归分析特发性膜性肾病患者缓解的相关因素，血清免疫学缓解时间每增加一个单位，患者达到缓解的风险降低13.5%（HR = 0.87，P = 0.016）。高滴度抗PLA2R抗体患者达到缓解的风险降低60.2%（HR = 0.39，P = 0.018）。 结论 不同剂量RTX的总临床缓解率相当，且不良反应未明显增加。RTX + TAC方案早期完全缓解率更高；血清学免疫缓解时间、高滴度抗PLA2R抗体与临床预后相关。
尚瑞华 , 李谦 , 郭明好 , 刘向东 , 王树龙 , 邢晖林 , 李瑾 . 不同剂量利妥昔单抗联合他克莫司治疗特发性膜性肾病的疗效对比[J]. 实用医学杂志, 2025 , 41(17) : 2740 -2747 . DOI: 10.3969/j.issn.1006-5725.2025.17.019
Objective To investigate the effect of two treatment regimens combining Tacrolimus （TAC） with different Rituximab （RTX） dosages， and to provide clinical reference for treatment strategies. Methods A retrospective analysis was conducted on patients diagnosed with idiopathic membranous nephropathy （IMN） and treated with RTX combined with TAC regimen （RTX + TAC group and low?dose RTX + TAC group） in The First Affiliated Hospital of Xinxiang Medical University. Propensity score matching （PSM） was performed at a 1∶1 ratio， and a total of 60 patients were enrolled， with 30 in each group. In low?dose RTX （375 mg/m2 at the first and fifteenth day respectively） + TAC group， if circulating B cells （CD19?） exceeded 5 cells/μL after 3 months， a 200 mg RTX infusion was administered. In RTX （1g at the first and fifteenth day respectively） + TAC group， if complete remission （CR） was not achieved by 6 months， an additional 1000 mg RTX infusion was administered. The incidence of CR， partial remission， and adverse events were followed up for 12 months after medication in both groups. Results （1） Both groups showed significant reductions in 24?hour proteinuria， with the RTX + TAC group demonstrating a notably higher decrease compared to the low?dose RTX + TAC group. Statistical differences were observed between the two groups at the 1st and 3rd months of treatment （P < 0.05）. Albumin levels gradually increased， and there were differences between the two groups at both the 1st and 3rd months （P < 0.05）. The anti?phospholipase A2 antibody levels decreased significantly after one month of treatment ［3.45（1.90， 22.10） vs. 3.28（8.30， 23.08） RU/mL］， P > 0.05. At 3 months of treatment， the overall clinical remission rate was 63.3% for the RTX + TAC group compared to 36.7% for the low?dose RTX + TAC group （P < 0.05）. At 12 months， the RTX + TAC group achieved an overall remission rate of 86.7%， while the low?dose RTX + TAC group reached 83.3%， showing no statistical significance （P > 0.05）. After one month of treatment， the RTX + TAC group achieved a complete serological immunological remission rate of 33.3%， significantly higher than the 3.3% in the low?dose RTX + TAC group （P < 0.05）. （2） The cumulative remission rate of the RTX + TAC group was higher than that of the low?dose RTX + TAC group during the first 6 months of follow?up. The remission rate in the low?dose RTX+TAC group increased significantly after 6 months. Log?rank test showed no statistical difference between the survival curves of the two groups （P = 0.37）. （3） Based on a multifactorial COX regression analysis of factors related to remission in patients with IMN， for every unit increase in serum immunological remission time， the risk of patients achieving remission decreased by 13.5% （HR = 0.87，P = 0.016）. The risk of remission for patients with high titers of anti?PLA2R antibodies decreased by 60.2% （HR = 0.39，P = 0.018）. Conclusions Different RTX dosages yielded comparable overall clinical remission rates without significantly increasing adverse events. RTX + TAC regimen achieves higher early CR rate. Serological remission time and high titer anti?PLA2R antibodies are associated with clinical outcomes.
Key words： idiopathic membranous nephropathy; rituximab; tacrolimus
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