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不同药物方案治疗难治性川崎病有效性和安全性的网状Meta分析
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| 篇名： | 不同药物方案治疗难治性川崎病有效性和安全性的网状Meta分析 |
| TITLE： | Network Meta-analysis of the Efficacy and Safety of Different Regimens in the Treatment of Refractory Kawasaki Disease |
| 摘要： | 目的：系统评价不同药物方案治疗难治性川崎病的疗效和安全性，为临床治疗提供循证参考。方法：计算机检索PubMed、Embase、Cochrane图书馆、中国知网、维普网、万方数据等，收集不同药物治疗方案用于难治性川崎病的随机对照研究（RCT）和队列研究，检索时限均为建库起至2021年3月。筛选文献，提取资料后采用改良版Jadad量表对RCT进行质量评价，采用纽卡斯尔-渥太华量表对队列研究进行质量评价。采用Stata16.0软件进行网状Meta分析。结果：共纳入29篇文献，其中15项为RCT、14项为队列研究；共计3112例患儿，涉及12种药物治疗方案，分别为2次静脉注射免疫球蛋白（IVIG）、2次IVIG+激素、2次IVIG+乌司他丁、首次IVIG、首次IVIG+激素、首次IVIG+环孢素、首次IVIG+依那西普、激素、激素+乌司他丁、乌司他丁、英夫利昔单抗、安慰剂。网状Meta分析结果显示，在冠状动脉损伤（CAL）发生率方面，使用2次IVIG+激素显著低于激素，首次IVIG+依那西普显著低于首次IVIG（P＜0.05）；网状Meta排序结果显示，CAL发生率的累积排序曲线下面积从低到高依次为激素＜乌司他丁＜2次IVIG＜首次IVIG＜首次IVIG+激素＜2次IVIG+激素＜英夫利昔单抗＜首次IVIG+环孢素＜首次IVIG+依那西普。不良反应发生率方面，与2次IVIG+激素和激素比较，2次IVIG、首次IVIG+依那西普均显著降低，英夫利昔单抗显著低于激素（P＜0.05）；网状Meta排序结果显示，不良反应发生率的累积排序曲线下面积由低到高依次为激素＜2次IVIG+激素＜首次IVIG+激素＜首次IVIG+环孢素＜首次IVIG＜2次IVIG＜首次IVIG+依那西普＜英夫利昔单抗。治疗后血清C反应蛋白（CRP）水平方面，与2次IVIG比较，2次IVIG+激素、2次IVIG+乌司他丁、激素均显著降低，2次IVIG+激素显著低于首次IVIG，2次IVIG+乌司他丁显著低于2次IVIG+激素、激素、激素+乌司他丁、首次IVIG、首次IVIG+激素、乌司他丁（P＜0.05）；网状Meta排序结果显示，治疗后血清CRP水平的累积排序曲线下面积由低到高依次为首次IVIG＜首次IVIG+激素＜2次IVIG＜激素+乌司他丁＜乌司他丁＜英夫利昔单抗＜激素＜2次IVIG+激素＜2次IVIG+乌司他丁。改善持续发热时间方面，各治疗措施两两比较差异均无统计学意义（P＞0.05）；网状Meta排序结果显示，持续发热时间的累积排序曲线下面积由低到高依次为首次IVIG＜安慰剂＜首次IVIG+环孢素＜激素＜2次IVIG+激素＜2次IVIG＜乌司他丁＜英夫利昔单抗。结论：首次IVIG联合依那西普在降低CAL发生率方面效果较好；英夫利昔单抗的不良反应发生率相对较低、退热效果较好；2次IVIG联合乌司他丁的抗炎效果较好。 |
| ABSTRACT： | OBJECTIVE：To systematically evaluat e the efficacy and safety of different regimens in the treatment of refractory Kawasaki disease ，and to provide evidence-based reference for clinical treatment. METHODS ：Retrieved from PubMed ，Embase， Cochrane Library ， CNKI， VIP， Wanfang database ，randomized controlled trials （RCTs）and cohort studies about different therapeutic regimens in the treatment of refractory 84206032。E-mail：liuyingzryy@163.com Kawasaki disease were collected during the inception to March 2021. After selecting the literature and extracting the data ，the quality of RCT was evaluated by modified Jadad scale ，and the quality of cohort st udy was evaluated by NOS scale. Network Meta-analysis was performed by using Stata 16.0 software. RESULTS ：A total of 29 literatures were included ，involving 15 RCTs and 14 cohort studies. A total of 3 112 patients and 12 therapeutic regimens were involved ，including twice IVIG ，twice IVIG+hormone，twice IVIG+ulinastatin ，first IVIG ，first time IVIG+hormone ，first time IVIG+cyclosporine ，first time IVIG+ etanercept，hormone，hormone+ulinastatin，ulinastatin，infliximab and placebo. The results of network Meta-analysis showed that in terms of the incidence of coronary artery injury （CAL），twice IVIG+hormone was significant lower than hormone ，and first time IVIG +etanercept was significant lower than first time IVIG （P＜0.05）. The sorting results of network Meta-analysis showed that area under cumulative ranking curve of CAL incidence in ascending order was hormone ＜ulinastatin＜twice IVIG ＜first time IVIG＜first IVIG+hormone ＜twice IVIG+hormone ＜infliximab＜first time IVIG+cyclosporin ＜first time IVIG+etanercept. In terms of the incidence of ADR ，compared with twice IVIG+ hormone and hormone ，twice IVIG and first time IVIG+etanercept were decreased significantly ；infliximab was significantly lower than hormone （P＜0.05）. The sorting results of network Meta-analysis showed that area under cumulative ranking curve of ADR incidence in ascending order was hormone ＜twice IVIG+hormone ＜first time IVIG+hormone ＜first time IVIG+cyclosporin ＜first time IVIG ＜twice IVIG ＜first time IVIG+etanercept ＜infliximab. In terms of the serum level of CRP ，compared with twice IVIG ，twice IVIG+hormone ，twice IVIG+ulinastatin and hormone were decreased significantly；twice IVIG+hormone was significantly lower than first time IVIG ；twice IVIG+ulinastatin were all significantly lower than twice IVIG+hormone ，hormone，hormone+ulinastatin，first time IVIG ，first time IVIG+hormone and ulinastatin （P＜0.05）. The sorting results of network Meta-analysis showed that area under cumulative ranking curve of serum CRP level in ascending order was first time IVIG ＜first time IVIG+hormone ＜twice IVIG ＜hormone+ulinastatin＜ulinastatin＜infliximab＜hormone＜twice IVIG+hormone＜twice IVIG+ulinastatin. In terms of improving persistent fever duration ，there was no statistical difference between pairwise treatment measures （P＞0.05）. The sorting results of network Meta-analysis showed area under cumulative ranking curve of persistent fever time in ascending order was first time IVIG ＜placebo＜first time IVIG+cyclosporine ＜hormone＜twice IVIG+ hormone＜twice IVIG ＜ulinastatin＜infamliximab. CONCLUSIONS ：The first time IVIG+etanercept has the best effect in reducing the incidence of CAL. Infliximab possesses a relatively low incidence of ADR and the best antipyretic effect. Twice IVIG + ulinastatin has the best anti-inflammatory effect. |
| 期刊： | 2021年第32卷第16期 |
| 作者： | 刘莹，张献，赵荣生 |
| AUTHORS： | LIU Ying，ZHANG Xian，ZHAO Rongsheng |
| 关键字： | 难治性川崎病；药物治疗方案；网状Meta分析；有效性；安全性 |
| KEYWORDS： | Refractory Kawasaki d isease；Drug therapeutic regimen ；Network Meta-analysis ；Efficacy；Safety |
| 阅读数： | 394 次 |
| 本月下载数： | 11 次 |
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