Network meta-analysis of the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease

CHEN Chang; HUANG Xiaohui; LYU Zhihao; HUANG Yuli

doi:10.6039/j.issn.1001-0408.2023.22.17

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Network meta-analysis of the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease

更新时间：2025-09-23

- Network meta-analysis of the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease
- ZHONGGUO YAOFANG Vol. 34, Issue 22, Pages: 2780-2786(2023)
- 作者机构：
  
  1.南方医科大学顺德医院（佛山市顺德区第一人民医院）儿科，广东;佛山　528300
  2.南方医科大学顺德医院（佛山市顺德区第一人民医院）心血管内科，广东佛山　528300
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.22.17
  CLC： R973;R725.4
- Received：16 May 2023，
  
  Revised：2023-10-26，
  
  Accepted：03 November 2023，
  
  Published：30 November 2023
- 稿件说明：
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陈昶,黄小惠,吕智濠,等.不同药物方案治疗儿童川崎病疗效和安全性的网状Meta分析 [J].中国药房,2023,34(22):2780-2786.

CHEN Chang,HUANG Xiaohui,LYU Zhihao,et al.Network meta-analysis of the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease[J].ZHONGGUO YAOFANG,2023,34(22):2780-2786.
陈昶,黄小惠,吕智濠,等.不同药物方案治疗儿童川崎病疗效和安全性的网状Meta分析 [J].中国药房,2023,34(22):2780-2786. DOI： 10.6039/j.issn.1001-0408.2023.22.17.

CHEN Chang,HUANG Xiaohui,LYU Zhihao,et al.Network meta-analysis of the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease[J].ZHONGGUO YAOFANG,2023,34(22):2780-2786. DOI： 10.6039/j.issn.1001-0408.2023.22.17.

摘要

目的

评价不同药物治疗方案用于儿童川崎病（KD）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the Cochrane Library、Medline、Embase、CINAHL、Web of Science、ProQuest、Google学术、中国知网、万方数据、百度学术数据库和世界卫生组织国际临床试验注册平台、ClinicalTrials.gov，收集在标准静脉注射免疫球蛋白（IVIG）疗法基础上给予糖皮质激素或环孢素或肿瘤坏死因子α（TNF-α）抑制剂（试验组）对比标准IVIG疗法（对照组）的随机对照试验（RCT），检索时限为建库至2023年2月28日。筛选文献、提取资料、评价文献质量后，采用Stata 14.2软件进行网状Meta分析。

结果

共纳入10项RCT，共计1 323例患儿；涉及6种干预措施，分别为标准IVIG疗法、糖皮质激素疗法、环孢素疗法、TNF-α抑制剂疗法、补救性糖皮质激素疗法和补救性TNF-α抑制剂疗法。网状Meta分析结果显示，使用糖皮质激素疗法患儿的4～8周冠状动脉瘤（CAA）发生率显著低于使用标准IVIG疗法和TNF-α抑制剂疗法患儿，使用补救性糖皮质激素疗法、补救性TNF-α抑制剂疗法患儿的4～8周CAA发生率均较使用糖皮质激素疗法患儿显著升高；其他干预措施间比较，差异均无统计学意义（

＞0

.05）；该发生率的网状Meta排序由低到高为糖皮质激素疗法＜环孢素疗法＜标准IVIG疗法＜补救性TNF-α抑制剂疗法＜补救性糖皮质激素疗法＜TNF-α抑制剂疗法。使用环孢素疗法患儿的初始IVIG抵抗发生率显著低于使用标准IVIG疗法患儿；其他干预措施间比较，差异均无统计学意义（

＞0.05）；该发生率的网状Meta排序由低到高为环孢素疗法＜糖皮质激素疗法＜TNF-α抑制剂疗法＜标准IVIG疗法。各干预措施间的不良反应发生率比较，差异均无统计学意义（

＞0.05）；该发生率的网状Meta排序由低到高为补救性TNF-α抑制剂疗法＜TNF-α抑制剂疗法＜标准IVIG疗法＜糖皮质激素疗法＜环孢素疗法。

结论

初始阶段给予糖皮质激素可显著减少KD患儿4～8周CAA的发生风险，给予环孢素可显著改善初始IVIG抵抗，在补救阶段使用TNF-α抑制剂的不良反应发生率可能最低。

Abstract

OBJECTIVE

To evaluate the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease， and to provide evidence-based reference for clinical treatment.

METHODS

Retrieved from the Cochrane Library， Medline， Embase， CINAHL， Web of Science， ProQuest， Google Scholar， CNKI， Wanfang Data， Baidu academic database， World Health Organization International Clinical Trials Registration Platform and ClinicalTrials.gov， randomized controlled trials （RCTs） about intravenous immunoglobulin （IVIG）+glucocorticoid or cyclosporine or tumor necrosis factor-alpha （TNF-α） blocker （trial group） versus standard IVIG therapy （control group） were collected from the establishment of the database to Feb. 28th， 2023. After screening the literature， extracting data， and evaluating the quality of the literature， Stata 14.2 software was used for network meta-analysis.

RESULTS

Ten RCTs with a total of 1 323 participants involving six measures were included： standard IVIG therapy， glucocorticoid therapy， cyclosporine therapy， TNF-α blocker therapy， remedial glucocorticoid therapy and remedial TNF-α blocker therapy. Results of network meta-analysis showed that the incidence of coronary artery aneurysms （CAA） at 4-8 weeks was significantly lower in patients receiving glucocorticoid therapy than receiving standard IVIG therapy and TNF-α blocker therapy. The incidences of CAA at 4-8 weeks in children treated with

remedial glucocorticoid therapy and remedial TNF-α blocker therapy were significantly higher than those treated with glucocorticoid therapy； there was no significant difference in the incidence of CAA at 4-8 weeks among other interventions （

＞0.05）； network meta-order of the incidence was glucocorticoid therapy＜cyclosporine therapy＜standard IVIG therapy＜remedial TNF-α blocker therapy＜remedial glucocorticoid therapy＜TNF-α blocker therapy. The incidence of initial IVIG resistance in children receiving cyclosporine therapy was significantly lower than those receiving standard IVIG therapy； there was no significant difference in the incidence of initial IVIG resistance among other interventions （

＞0.05）； network meta-order of the incidence was cyclosporine therapy＜glucocorticoid therapy＜TNF-α blocker therapy＜standard IVIG therapy. There was no significant difference in the incidence of ADR among different interventions （

＞0.05）； network meta-order of the incidence was remedial TNF-α blocker therapy＜TNF-α blocker therapy＜standard IVIG therapy＜glucocorticoid therapy＜cyclosporine therapy.

CONCLUSIONS

Glucocorticoid therapy at the initial treatment can significantly reduce the risk of CAA at 4-8 weeks in children with Kawasaki disease； cyclosporine has a significant effect on improving initial IVIG resistance， and the use of TNF-α blocker in the remedial stage may have the lowest incidence of adverse reactions.

关键词

Keywords

references

BURNS J C ， GLODÉ M P . Kawasaki syndrome [J ] . Lancet ， 2004 ， 364 （ 9433 ）： 533 - 544 .

YOUNGER D S . Epidemiology of the vasculitides [J ] . Neurol Clin ， 2019 ， 37 （ 2 ）： 201 - 217 .

XIE L P ， YAN W L ， HUANG M ， et al . Epidemiologic features of Kawasaki disease in Shanghai from 2013 through 2017 [J ] . J Epidemiol ， 2020 ， 30 （ 10 ）： 429 - 435 .

MCCRINDLE B W ， ROWLEY A H ， NEWBURGER J W ， et al . Diagnosis，treatment，and long-term management of Kawasaki disease：a scientific statement for health professionals from the American Heart Association [J ] . Circulation ， 2017 ， 135 （ 17 ）： e927 - e999 .

KOBAYASHI T ， AYUSAWA M ， SUZUKI H ， et al . Revision of diagnostic guidelines for Kawasaki disease：6th revised edition [J ] . Pediatr Int ， 2020 ， 62 （ 10 ）： 1135 - 1138 .

UEHARA R ， BELAY E D ， MADDOX R A ， et al . Ana-lysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan [J ] . Pediatr Infect Dis J ， 2008 ， 27 （ 2 ）： 155 - 160 .

SHINOHARA M ， SONE K ， TOMOMASA T ， et al . Corticosteroids in the treatment of the acute phase of Kawasaki disease [J ] . J Pediatr ， 1999 ， 135 （ 4 ）： 465 - 469 .

BURNS J C ， MASON W H ， HAUGER S B ， et al . Infli-ximab treatment for refractory Kawasaki syndrome [J ] . J Pediatr ， 2005 ， 146 （ 5 ）： 662 - 667 .

SUZUKI H ， TERAI M ， HAMADA H ， et al . Cyclosporin A treatment for Kawasaki disease refractory to initial and additional intravenous immunoglobulin [J ] . Pediatr Infect Dis J ， 2011 ， 30 （ 10 ）： 871 - 876 .

HIGGINS J P T ， SAVOVIĆ J ， PAGE M J ， et al . Assessing risk of bias in a randomized trial [J ] . Cochrane handbook for systematic reviews of interventions ， 2019 ， 6 ： 205 - 228 .

汪徐林，秦正积，陆益花，等 . Stata软件在网状Meta分析中的应用 [J ] . 现代预防医学， 2016 ， 43 （ 19 ）： 3461 - 3464，3482 .

WANG X L ， QIN Z J ， LU Y H ， et al . Network meta-analysis and its implementation by Stata [J ] . Mod Prev Med ， 2016 ， 43 （ 19 ）： 3461 - 3464，3482 .

SUNDEL R P ， BAKER A L ， FULTON D R ， et al . Corticosteroids in the initial treatment of Kawasaki disease： report of a randomized trial [J ] . J Pediatr ， 2003 ， 142 （ 6 ）： 611 - 616 .

NEWBURGER J W ， SLEEPER L A ， MCCRINDLE B W ， et al . Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease [J ] . N Engl J Med ， 2007 ， 356 （ 7 ）： 663 - 675 .

KOBAYASHI T ， SAJI T ， OTANI T ， et al . Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease（RAISE study）：a randomised，open-label，blinded- endpoints trial [J ] . Lancet ， 2012 ， 379 （ 9826 ）： 1613 - 1620 .

OGATA S ， OGIHARA Y ， HONDA T ， et al . Corticosteroid pulse combination therapy for refractory Kawasaki disease：a randomized trial [J ] . Pediatrics ， 2012 ， 129 （ 1 ）： e17 - e23 .

TREMOULET A H ， JAIN S ， JAGGI P ， et al . Infliximab for intensification of primary therapy for Kawasaki disease：a phase 3 randomised，double-blind，placebo-controlled trial [J ] . Lancet ， 2014 ， 383 （ 9930 ）： 1731 - 1738 .

YOUN Y ， KIM J ， HONG Y M ， et al . Infliximab as the first retreatment in patients with Kawasaki disease resistant to initial intravenous immunoglobulin [J ] . Pediatr Infect Dis J ， 2016 ， 35 （ 4 ）： 457 - 459 .

HAMADA H ， SUZUKI H ， ONOUCHI Y ， et al . Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin（KAICA）：a randomised controlled，open-label，blinded-endpoints，phase 3 trial [J ] . Lancet ， 2019 ， 393 （ 10176 ）： 1128 - 1137 .

PORTMAN M A ， DAHDAH N S ， SLEE A ， et al . Etanercept with IVIG for acute Kawasaki disease：a randomized controlled trial [J ] . Pediatrics ， 2019 ， 143 （ 6 ）： e20183675 .

WANG Z P ， CHEN F Y ， WANG Y F ， et al . Methylprednisolone pulse therapy or additional IVIG for patients with IVIG-resistant Kawasaki disease [J ] . J Immunol Res ， 2020 ， 2020 ： 4175821 .

BURNS J C ， ROBERTS S C ， TREMOULET A H ， et al . Infliximab versus second intravenous immunoglobulin for treatment of resistant Kawasaki disease in the USA（KIDCARE）：a randomised，multicentre comparative effectiveness trial [J ] . Lancet Child Adolesc Health ， 2021 ， 5 （ 12 ）： 852 - 861 .

ORENSTEIN J M ， SHULMAN S T ， FOX L M ， et al . Three linked vasculopathic processes characterize Kawasaki disease：a light and transmission electron microscopic study [J ] . PLoS One ， 2012 ， 7 （ 6 ）： e38998 .

NAOE S ， TAKAHASHI K ， MASUDA H ， et al . Kawasaki disease：with particular emphasis on arterial lesions [J ] . Acta Pathol Jpn ， 1991 ， 41 （ 11 ）： 785 - 797 .

MUTA H ， ISHII M ， YASHIRO M ， et al . Late intravenous immunoglobulin treatment in patients with Kawasaki disease [J ] . Pediatrics ， 2012 ， 129 （ 2 ）： e291 - e297 .

OKADA Y ， SHINOHARA M ， KOBAYASHI T ， et al . Effect of corticosteroids in addition to intravenous gamma globulin therapy on serum cytokine levels in the acute phase of Kawasaki disease in children [J ] . J Pediatr ， 2003 ， 143 （ 3 ）： 363 - 367 .

BROWN T J ， CRAWFORD S E ， CORNWALL M L ， et al . CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease [J ] . J Infect Dis ， 2001 ， 184 （ 7 ）： 940 - 943 .

DE GRAEFF N ， GROOT N ， OZEN S ， et al . European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease：the SHARE initiative [J ] . Rheumatology ， 2019 ， 58 （ 4 ）： 672 - 682 .

ONOUCHI Y ， SUZUKI Y ， SUZUKI H ， et al . ITPKC and CASP3 polymorphisms and risks for IVIG unresponsiveness and coronary artery lesion formation in Kawasaki disease [J ] . Pharmacogenomics J ， 2013 ， 13 （ 1 ）： 52 - 59 .

FURUKAWA S ， MATSUBARA T ， JUJOH K ， et al . Peripheral blood monocyte/macrophages and serum tumor necrosis factor in Kawasaki disease [J ] . Clin Immunol Immunopathol ， 1988 ， 48 （ 2 ）： 247 - 251 .

HIRONO K ， KEMMOTSU Y ， WITTKOWSKI H ， et al . Infliximab reduces the cytokine-mediated inflammation but does not suppress cellular infiltration of the vessel wall in refractory Kawasaki disease [J ] . Pediatr Res ， 2009 ， 65 （ 6 ）： 696 - 701 .

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