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中国循证儿科杂志

中国循证儿科杂志 ›› 2022, Vol. 17 ›› Issue (1): 35-38.

• 论著 • 上一篇    下一篇

免疫球蛋白无应答川崎病再次免疫球蛋白、英夫利昔单抗和激素治疗队列研究

彭宇,刘小惠,欧阳倩,段炤   

  1. 江西省儿童医院风湿免疫科南昌，330006

  • 收稿日期:2021-12-23 修回日期:2022-01-04 出版日期:2022-02-25 发布日期:2022-02-25
  • 通讯作者: 刘小惠

Treatment of refractory Kawasaki disease with IVIG, infliximab or corticosteroids: A cohort study

#br# PENG Yu, LIU Xiaohui, OUYANG Qian, DUAN Zhao#br#   

  1. Department of Rheumatology, Jiangxi Province Children's Hospital, Nanchang 330006, China
  • Received:2021-12-23 Revised:2022-01-04 Online:2022-02-25 Published:2022-02-25
  • Contact: LIU Xiaohui, email: 851724846@qq.com

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摘要： 背景：IVIG无应答KD患儿的治疗方案包括再次IVIG、英夫利昔单抗(IFX)和激素(IMP)，目前不同治疗方案的疗效评价不一。 目的：IVIG无应答KD患儿再次IVIG、IFX和IMP治疗效果比较。 研究设计：队列研究。 方法：以IVIG无应答KD患儿为队列人群，再次治疗和补救治疗（再次治疗无反应）在江西省儿童医院（我院）中进行，且能按时来我院随访行超声心动图（起病3个月内冠状动脉超声）。初次治疗均为起病10 d 内给予 IVIG 2 g·kg-1+口服阿司匹林50 mg·kg-1·d-1，根据家长意愿选择再次和补救IVIG（2 g·kg-1，1次）、IFX（5 mg·kg-1，1次）或IMP（30 mg·kg-1·d-1，3 d）治疗，应答为再次或补救治疗36 h内体温降至正常水平。 主要结局指标：总治疗应答率（IVIG或IFX或IMP再次+补救治疗应答人数/IVIG或IFX或IMP使用人数），起病3个月内冠状动脉Z值。 结果：2018年1月至2020年12月，73例IVIG无应答KD患儿进入本文分析。IVIG组30例，IFX组25例，IMP组18例。3组患儿年龄、性别、首剂IVIG治疗前发热时间、再次治疗前发热时间、初始治疗前WBC、N、Hb和CRP差异均无统计学意义（P＞0.05）；3组发热时间差异有统计学意义（P=0.024），总发热时间IFX组短于IVIG组和IMP组，差异有统计学意义（P分别为0.012和0.016）。IFX组再次治疗应答率（24/25，96.0%）高于IVIG组（17/30，56.7%）和IMP组（12/18，66.7%），差异均有统计学意义（P分别为0.001和0.015）。IFX组1例再次治疗无应答，予IVIG后应答；IVIG组13例再次治疗无应答，7例予IMP、6例予IFX均应答；IMP组6例再次治疗无应答，予IVIG后4例应答，2例仍无应答，再予IFX后应答。总体应答率为IFX组（32/33，97.0%）高于IMP组（19/25，76.0%）和IVIG组（22/37，59.4%），差异均有统计学意义（P=0.035, P<0.001）。再次治疗后发热时间IFX组短于IVIG组和IMP组，差异有统计学意义（P分别为0.001和0.026），补救治疗3组发热时间差异无统计学意义（P=0.086)。初始治疗后3个月时冠状动脉Z值IFX组小于IVIG组和IMP组，差异有统计学意义（P分别为0.001和0.002）。 结论：IVIG无应答KD的再次治疗可首选IFX，其次为IMP或IVIG。

关键词: 川崎病, 耐药, 免疫球蛋白, 英夫利昔, 甲强龙

Abstract: Background: Therapeutic agents of refractory Kawasaki disease（KD） include IVIG, corticosteroids, and infliximab(IFX). However, the evaluation of therapeutic efficacy of those agents is not unified. Objective: To observe the therapeutic effects of IVIG, intravenous methylprednisolone（IMP）, and IFX on patients with refractory KD. Design: Cohort study. Methods: Patients with refractory KD who received retreatment and rescue therapy in Jiangxi Province Children's Hospital were taken as the cohort population. They were required to receive the echocardiographic followup of coronary arteries at the time of 3 months after the onset. IVIG (2 g·kg-1) plus oral aspirin (50 mg/ kg/day) was performed as initial treatment within 10 days of the onset. Retreatment and rescue therapy included IVIG(2 g·kg-1), IMP(30 mg·kg-1, 3 d), and IFX (5 mg·kg-1). Parents of these patients could choose the therapeutic agent according to their own will. Response was defined as patients with refractory KD had normal body temperature within 36 hours after the end of the retreatment therapy or rescue therapy. Main outcome measures: The response rate of total treatment, and coronary artery internal diameters (Zscore) at the time of 3 months after the initial treatment. Results: There were 73 patients with refractory KD from January 2018 to December 2020 in this study, including 30, 25 and 18 cases in IVIG retreatment group, IFX group and IMP group, respectively. There were no significant difference in age, gender, duration of fever before the initial treatment, duration of fever before rescue therapy, and laboratory parameters before the initial treatment (white blood cells, neutrophils, hemoglobin and Creactive protein). The fever duration of IFX group was shorter than that of IVIG group and IMP group (P=0.012, P=0.016, respectively). The difference in fever duration among the three groups was statistically significant(P=0.024). The retreatment response rate of IFX group was higher than that of IVIG group and IMP group (P=0.001, P=0.015, respectively). One patient in IFX group did not respond to the retreatment of IFX and respond to the rescue therapy of IVIG. Thirteen patients in IVIG group did not respond to the retreatment therapy, among which 7 responded to rescue therapy of IMP, and 6 responded to rescue therapy of IFX. Six patients in IMP group did not respond to the retreatment therapy, and 4 of them responded to the rescue therapy of IVIG, 2 of them did not respond until the rescue therapy of IFX. The total response rate of IFX regimen was higher than that of IVIG and IMP(P=0.035, P<0.001, respectively). The fever duration after retreatment in IFX group were shorter than that of IVIG group and IMP group (P=0.001, P=0.026, respectively). The Zscore at the time of 3 months after the initial treatment in IFX group were significantly lower than that of IVIG group and IMP group (P=0.001, P=0.002, respectively). Conclusion: IFX could be used as the first drug for the treatment of patients with refractory KD followed by IMP and IVIG.

Key words: Kawasaki disease, Refractory, IVIG, Infliximab, Methylprednisolone