饶思捷 李云云 关扬婷 沈清

[摘要]目的系统评价激素联合来氟米特与其他免疫抑制剂比较治疗特发性膜性肾病的疗效。方法计算机检索中英文數据库，包括从建库至2021年3月31日发表的与激素联合来氟米特治疗特发性膜性肾病有关的随机对照研究，对纳入文献采用WinBugs 14.3和 Stata 15.0软件进行网状 meta 分析。结果共纳入27个随机对照试验，包括1641例患者。网状 meta 分析显示：在均联合激素的基础上，随访至6个月的完全缓解率，来氟米特联合环孢素高于环磷酰胺[OR=3.06，95%CI （1.14，8.22），P=0.006];他克莫司高于来氟米特[OR=2.47，95%CI （1.31，4.64），P=0.016]或环磷酰胺[OR=2.92，95%CI （1.65，5.14），P=0.010]。累积排序概率曲线下面积（ SUCRA ）显示：来氟米特联合环孢素（SUCRA=82.5）的疗效最佳;总缓解率方面，他克莫司高于来氟米特[OR=2.26，95%CI （1.27，4.00），P=0.030]，他克莫司或来氟米特联合环孢素均高于环磷酰胺[OR=2.46，95%CI （1.45，4.19），P=0.012; OR=3.69，95%CI （1.49，9.15），P=0.003];来氟米特联合环孢素疗效最佳（SUCRA=92.3）。在不良反应方面，他克莫司发生肝酶异常（SUCRA=83.2）和白细胞减少（SUCRA=97.3）的风险最低，来氟米特最不易出现消化道反应（ SUCRA=76.6）。结论在联合激素治疗特发性膜性肾病的基础上，来氟米特的疗效优于环磷酰胺;来氟米特联合环孢素在短期内的疗效与他克莫司不相上下，且均优于单独使用来氟米特或环磷酰胺，其长期疗效未来仍需更多高质量研究予以探究。

[关键词]激素;来氟米特;特发性膜性肾病;网状 meta 分析

[中图分类号] R692  [文献标识码] A   [文章编号]2095-0616（2021）24-0042-07

Reticular meta-analysis in comparing hormone combined with leflunomide and other immunosuppressants in the treatment of idiopathic membranous nephropathy

RAO  Sijie1      LI  Yunyun2      GUAN  Yangting1      SHEN  Qing1

1. Department of Nephrology， the First Affiliated Hospital of Chongqing Medical University， Chongqing 400016， China;2. Yongchuan Hospital of Chongqing Medical University， Chongqing 402160， China

[Abstract] Obj e ctiveT o sys tematically evaluate the therapeutic efficacy of hormone com bined with leflunomide compared with other immunosuppressants in the treatment of idiopathic membranous neph r opathy .Methods  T he Chines e and Englis h databas es wer e s ear ched by com puter ， inclu ding the randomized controlled research related to hormone combined with  leflunomide in the treatment of idiopathic membranous nephropathy published from the establishment of the database to March 31， 2021. The included literatures were performed by reticular meta -analysis by using WinBugs 14.3 and Stata 15.0 software . Results A total of 27 randomized controlled trials were fitted in， including 1641 patients . Reticular meta - analys is s howed that on the bas is of all com binedhormones ， the complete rem is s ion rate of leflunomide combined with cyclosporine was higher than that of cyclophosphamide （ OR=3.06， 95%CI[1.14， 8.22]， P=0.006）. Tacrolimus was higher than leflunomide （ OR=2.47， 95%CI[1.31， 4.64]， P =0.016） or cyclophosphamide （ OR =2.92，95% CI[1.65， 5.14]， P =0.010）. The area under cumulative ranking probability curve （SUCRA） showed that leflunomide combined with cyclosporine （SUCRA=82.5） had the best therapeutic efficacy . In terms of total remission rate， tacrolimus was higher than leflunomide （OR=2.26， 95%CI[1.27，4.00]， P=0.030）; Tacrolimus or leflunomide combined with cyclosporine are higher thancyclophosphamide（OR=2.46，95%CI[1.45， 4.19]，P=0.012; OR=3.69，95%CI[1.49， 9.15]， P=0.003）.Leflunomidecombined with cyclosporine had the best therapeutic  efficacy （SUCRA=92.3）.In terms of adverse reactions， tacrolimus had the lowest risk of liver enzyme abnormality （SUCRA=83.2） and leukopenia （SUCRA=97.3）， and leflunomide was the least prone to gastrointestinal reactions （SUCRA=76.6）. Conclusion On the basis of combined hormone therapy for idiopathic membranous nephropathy， leflunomide is more effective than cyclophosphamide . The short -term therapeutic efficacy of leflunomide combined with cyclosporine is comparable to that of tacrolimus， and they are both superior to that of leflunomide or cyclophosphamide alone . The long-term therapeutic efficacy of leflunomide combined with cyclosporine still needs more high- quality research in the future .

[Key words] Hormones; Leflunomide; Idiopathic membranous nephropathy; Reticular meta-analysis

特发性膜性肾病（idiopathic membranous nephropathy，IMN）是一种自身免疫性疾病，可累及肾脏足细胞[1]。IMN 病情复杂，多数患者会发展为难治性肾病甚至终末期肾病，因此其治疗药物的选择至关重要[2]。……