Efficacy and Safety of Different Pharmacological Interventions for Progressive IgA Nephropathy：a Network Meta-analysis

doi:10.12114/j.issn.1007-9572.2020.00.637

Abstract

Abstract: Background　Patients with progressive IgA nephropathy （IgAN）have a significantly increased risk of developing end-stage renal disease.However，many available treatments for progressive IgAN have a high rate of side effects and insignificant long-term benefits.So choosing an appropriate regimen with good safety and efficacy is essential for the treatment of this disease.Objective　To evaluate the efficacy and safety of different pharmacological interventions in the treatment of progressive IgAN by network meta-analysis.Methods　Randomized controlled trials （RCTs）about different pharmacological interventions for progressive IgAN were searched in PubMed，EMBase，The Cochrane Library，CNKI，Wanfang Data，CBM and VIP databases from inception to March 31，2020.Literature screening，data extraction and risk of bias evaluation were performed by two reviewers independently.Stata 14.0 and GeMTC 0.14.3 were used to conduct a network Meta-analysis of the efficacy，improvement in 24 h urinary protein and creatinine levels and treatment-emergent adverse events in these patients with different pharmacological interventions.Results　A total of 38 RCTs were included，including 3 034 patients，and 10 intervention programs：Prednisone （Pred），mycophenolate mofetil （MMF）combined with Pred，cyclophosphamide （CTX）combined with Pred，leflunomide （LEF）combined with Pred，cyclosporine （CsA）combined with Pred，traditional Chinese medicine （TCM）combined with immunosuppressant （ISD），TCM，MMF，LEF and supportive treatment.Network meta-analysis showed that：（1）In terms of the overall resonse，TCM combined with ISD was more superior to TCM〔RR=2.27，95%CI（1.14，4.65）〕，LEF combined with Pred〔RR=2.14，95%CI（1.05，4.45）〕，CTX combined Pred〔RR=3.92，95%CI（2.06，7.37）〕，Pred〔RR=3.57，95%CI（2.11，6.32）〕，LEF〔RR=5.88，95%CI（1.03，37.17）〕and supportive support treatment 〔RR=6.25，95%CI（2.86，13.82）〕（P<0.05）.Compared with CTX combined with Pred，CSA combined with Pred 〔RR=3.73，95%CI（1.54，9.10）〕 and MMF combined with Pred 〔RR=2.37，95%CI（1.33，4.44）〕 had more favorable overall resonse（P<0.05）.Compared with Pred，CSA combined with Pred 〔RR=3.37，95%CI（1.52，8.13）〕 and MMF combined with Pred 〔RR=2.13，95%CI（1.24，4.13）〕 had more favorable overall resonse（P<0.05）.（2）The incidence of adverse reactions of MMF combined with Pred〔RR=0.21，95%CI（0.09，0.49）〕，LEF combined with Pred〔RR=0.16，95%CI（0.08，0.34）〕，TCM combined with ISD〔RR=0.31，95%CI（0.13，0.72）〕，TCM〔RR=0.05，95%CI（0.01，0.22）〕，Pred〔RR=0.37，95%CI（0.18，0.73）〕and supportive treatment〔RR=0.24，95%CI（0.06，0.87）〕was lower than that of CTX combined with Pred（P<0.05）.LEF combined with Pred had a lower incidence of adverse reactions than CsA combined with Pred〔RR=0.28，95%CI（0.09，0.90）〕（P<0.05）.（3）For reducing 24 h urinary protein，MMF combined with Pred was more superior to CTX combined with Pred〔MD=0.55，95%CI（0.25，0.85）〕，LEF combined with Pred〔MD=0.53，95%CI（0.10，0.97）〕，supportive treatment〔MD=0.72，95%CI（0.24，1.20）〕，TCM〔MD=0.66，95%CI（0.16，1.15）〕，and MMF〔MD=0.62，95%CI（0.02，1.22）〕（P<0.05）.TCM combined with ISD lowered proteinuria level more significantly than CTX combined with Pred〔MD=0.42，95%CI（0.09，0.75）〕，LEF combined with Pred〔MD=0.40，95%CI（0.03，0.79）〕，Pred〔MD=0.41，95%CI（0.15，0.67）〕，TCM〔MD=0.53，95%CI（0.08，0.98）〕，and supportive treatment〔MD=0.59，95%CI（0.19，0.99）〕（P<0.05）.Compared with CTX combined with Pred〔MD=0.55，95%CI（0.04，1.06）〕，Pred〔MD=0.53，95%CI（0.07，1.01）〕，and supportive treatment〔MD=0.71，95%CI（0.11，1.32）〕，CsA combined with Pred had better effect on reducing proteinuria level （P<0.05）.（4）For reducing serum creatinine level，TCM combined with ISD was better than LEF combined with Pred 〔MD=19.69，95%CI（0.68，39.49）〕 and Pred 〔MD=14.50，95%CI（1.49，28.04）〕（P<0.05）.MMF combined with Pred showed better effects on lowering serum creatinine level than MMF〔MD=45.66，95%CI（0.40，91.16）〕（P<0.05）.Conclusion　Considering the results，MMF combined with Pred，TCM combined with ISD， LEF combined with Pred have better clinical efficacy and higher safety in the treatment of progressive IgAN.

Key words: Glomerulonephritis, IGA；Progressive IgA nephropathy；Efficacy；Safety；Randomized controlled trial；Network meta-analysis

摘要： 背景　进展性IgA肾病（IgAN）患者发展为终末期肾脏疾病的风险明显增加。然而，目前关于进展性IgAN的诸多治疗方案存在不良反应大、长期治疗收益不明显等特点。因此，选择安全有效的干预方案，对进展性IgAN的治疗至关重要。目的　评价不同药物治疗方案干预进展性IgAN的疗效性和安全性。方法　计算机检索PubMed、EMBase、The Cochrane Library、中国知网、万方数据知识服务平台、中国生物医学文献数据库（CBM）和维普网数据库中关于不同药物治疗方案干预进展性IgAN的随机对照试验（RCTs），检索时限为建库至2020-03-31。由2名研究者独立筛选文献、提取资料和评价纳入研究的偏倚风险后，采用Stata 14.0和GeMTC 0.14.3统计软件对不同药物治疗方案干预进展性IgAN的总有效率、24 h尿蛋白定量、肌酐水平、不良反应发生率等进行网状Meta分析。结果　共纳入38个RCTs研究，包括3 034例患者，包含10种干预方案：激素（Pred）、霉酚酸酯（MMF）联合Pred、环磷酰胺（CTX）联合Pred、来氟米特（LEF）联合Pred、环孢素（CsA）联合Pred、中药疗法（TCM）联合免疫抑制剂（ISD）、单用TCM、单用MMF、单用LEF及支持治疗。网状Meta分析结果显示：（1）总有效率：TCM联合ISD优于单用TCM治疗〔RR=2.27，95%CI（1.14，4.65）〕、LEF联合Pred〔RR=2.14，95%CI（1.05，4.45）〕、CTX联合Pred〔RR=3.92，95%CI（2.06，7.37）〕、单用Pred〔RR=3.57，95%CI（2.11，6.32）〕、单用LEF〔RR=5.88，95%CI（1.03，37.17）〕及支持治疗〔RR=6.25，95%CI（2.86，13.82）〕；CsA联合Pred〔RR=3.73，95%CI（1.54，9.10）〕及MMF联合Pred〔RR=2.37，95%CI（1.33，4.44）〕优于CTX联合Pred，CsA联合Pred〔RR=3.37，95%CI（1.52，8.13）〕及MMF联合Pred〔RR=2.13，95%CI（1.24，4.13）〕优于单用Pred（P<0.05）。（2）不良反应发生率：MMF联合Pred〔RR=0.21，95%CI（0.09，0.49）〕、LEF联合Pred〔RR=0.16，95%CI（0.08，0.34）〕、TCM联合ISD〔RR=0.31，95%CI（0.13，0.72）〕、单用TCM〔RR=0.05，95%CI（0.01，0.22）〕、单用Pred〔RR=0.37，95%CI（0.18，0.73）〕及支持治疗〔RR=0.24，95%CI（0.06，0.87）〕均低于CTX联合Pred，LEF联合Pred低于CsA联合Pred〔RR=0.28，95%CI（0.09，0.90）〕（P<0.05）。（3）24 h尿蛋白定量：MMF联合Pred优于CTX联合Pred〔MD=0.55，95%CI（0.25，0.85）〕、LEF联合Pred〔MD=0.53，95%CI（0.10，0.97）〕、支持治疗〔MD=0.72，95%CI（0.24，1.20）〕、单用TCM〔MD=0.66，95%CI（0.16，1.15）〕、单用MMF〔MD=0.62，95%CI（0.02，1.22）〕，TCM联合ISD优于CTX联合Pred〔MD=0.42，95%CI（0.09，0.75）〕、LEF联合Pred〔MD=0.40，95%CI（0.03，0.79）〕、单用Pred〔MD=0.41，95%CI（0.15，0.67）〕、单用TCM〔MD=0.53，95%CI（0.08，0.98）〕及支持治疗〔MD=0.59，95%CI（0.19，0.99）〕，CsA联合Pred优于CTX联合Pred〔MD=0.55，95%CI（0.04，1.06）〕、单用Pred〔MD=0.53，95%CI（0.07，1.01）〕及支持治疗〔MD=0.71，95%CI（0.11，1.32）〕（P<0.05）。（4）肌酐水平：TCM联合ISD优于LEF联合Pred〔MD=19.69，95%CI（0.68，39.49）〕及单用Pred〔MD=14.50，95%CI（1.49，28.04）〕，MMF联合Pred优于单用MMF〔MD=45.66，95%CI（0.40，91.16）〕（P<0.05）。结论　MMF联合Pred、TCM联合ISD、LEF联合Pred方案治疗进展性IgAN的临床疗效较好，安全性较高。

关键词: 肾小球肾炎, IGA；进展性IgA肾病；疗效；安全性；随机对照试验；网状Meta分析

LIU Tongtong,WANG Yuyang,YANG Liping, et al. Efficacy and Safety of Different Pharmacological Interventions for Progressive IgA Nephropathy：a Network Meta-analysis　[J]. Chinese General Practice, 2021, 24(8): 989-1000. DOI: 10.12114/j.issn.1007-9572.2020.00.637.
刘童童,王宇阳,杨丽平等. 不同药物治疗方案干预进展性IgA肾病有效性和安全性的网状Meta分析[J]. 中国全科医学, 2021, 24(8): 989-1000. DOI: 10.12114/j.issn.1007-9572.2020.00.637.

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