Division of Pediatric Rheumatology, University of Alabama, 1600 7th Avenue S, CPPN G10, Birmingham, AL, 35233, USA.
University of Alabama School of Medicine, 1670 University Blvd, Birmingham, AL, 35233, USA.
Pediatr Rheumatol Online J. 2019 Nov 27;17(1):77. doi: 10.1186/s12969-019-0380-z.
Evidence remains contradictory regarding second-line therapy in patients with Kawasaki disease (KD) refractory to initial intravenous immunoglobulin (IVIg). The objective of this study aims to evaluate the efficacy and safety of three treatments [i.e. a second IVIg infusion, methylprednisolone (IVMP), and infliximab (IFX)] in patients with refractory KD.
A systematic search of PubMed, Embase, Cochrane, and ClinicalTrials.gov using predefined MeSH terms was performed from 1990 through 2017. Relevance screening was performed by two independent reviewers. Inclusion criteria included English-only, original clinical data. Eight studies met the inclusion criteria. Fever resolution, coronary lesions, and adverse event outcomes were extracted and pooled for analysis.
Of the 388 patients included from the 8 studies analyzed, a majority received a second IVIg dose (n = 263, 68%). Fever resolution was comparable between IVIg (72%) and IVMP (73%). IFX (88%) significantly increased fever resolution by approximately 20% compared to IVIg re-dose (RR 1.2; [95% CI: 1.1-1.4]; p = 0.03) and IVMP (RR 1.2; [95% CI: 1.0-1.5]; p = 0.04). Clinical significance of differences in coronary outcomes remains unclear.
This combined analysis was limited due to variability in design and data reporting methods between the studies and risk of bias. In the absence of a clinical trial, IFX monotherapy as second-line treatment should be considered in patients who fail to respond to initial IVIg. This conclusion is based on a systematic review of the literature with pooled outcome data analysis suggesting IFX is more effective in fever resolution compared to a second IVIg dose and IVMP.
对于最初静脉注射免疫球蛋白（IVIg）治疗无反应的川崎病（KD）患者，二线治疗的证据仍然存在争议。本研究旨在评估三种治疗方法[即第二次 IVIg 输注、甲泼尼龙（IVMP）和英夫利昔单抗（IFX）]在难治性 KD 患者中的疗效和安全性。
通过预设的 MeSH 术语，从 1990 年到 2017 年，对 PubMed、Embase、Cochrane 和 ClinicalTrials.gov 进行了系统搜索。两名独立审查员进行了相关性筛选。纳入标准包括仅为英文、原始临床数据。八项研究符合纳入标准。提取并汇总了退热、冠状动脉病变和不良事件结局的数据进行分析。
在分析的 8 项研究中，有 388 名患者被纳入，其中大部分患者接受了第二次 IVIg 剂量（n=263，68%）。IVIg（72%）和 IVMP（73%）的退热效果相当。与 IVIg 再剂量（RR 1.2；[95%CI：1.1-1.4]；p=0.03）和 IVMP（RR 1.2；[95%CI：1.0-1.5]；p=0.04）相比，IFX（88%）可使退热效果提高约 20%。冠状动脉结局差异的临床意义仍不清楚。
由于研究之间设计和数据报告方法的差异以及偏倚风险，本次联合分析受到限制。在没有临床试验的情况下，对于初始 IVIg 治疗无反应的患者，应考虑将 IFX 单药作为二线治疗。这一结论是基于对文献的系统评价和汇总结局数据分析得出的，表明与第二次 IVIg 剂量和 IVMP 相比，IFX 在退热方面更有效。
