Comparison of second-line therapy in IVIg-refractory Kawasaki disease: a systematic review

Abstract

BackgroundEvidence 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.MethodsA 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.ResultsOf 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.ConclusionsThis 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.

Randomized trial of different initial intravenous immunoglobulin regimens in Kawasaki disease

“…If KD patients who receive 1 g/kg IVIG as initial treatment develop IVIG resistance, more aggressive additional treatment could therefore be given such as infliximab. Infliximab, a monoclonal antibody against tumor necrosis factor α, is more effective in fever resolution compared to a second IVIG dose 20,21 . Further studies are needed to determine the efficacy of infliximab in KD patients who do not respond to the initial 1 g/kg IVIG.…”

“…Infliximab, a monoclonal antibody against tumor necrosis factor α, is more effective in fever resolution compared to a second IVIG dose. 20 , 21 Further studies are needed to determine the efficacy of infliximab in KD patients who do not respond to the initial 1 g/kg IVIG. If this problem is properly handled, 1 g/kg IVIG could be a cost‐effective treatment option for KD patients.…”

Utilizing Single-cell RNA Sequencing for Analyzing the Characteristics of PBMC in Patients with Kawasaki Disease

“…KD is a common cause of vasculitis in childhood, which is characterized by fever and mucocutaneous features [13]. Current studies suggest that the regulation of T cell activation determines the susceptibility of KD and the severity of coronary artery lesions.…”

Kawasaki disease in siblings and a review of drug treatment

“… 27 It is concluded that infliximab monotherapy should be considered in patients, who fail to respond to initial IVIG, based on a systematic review of the literature with pooled outcome data analysis suggesting infliximab is more effective in fever resolution compared to a second IVIG dose and intravenous methylprednisolone. 27 According to a 2019-Cochrane review, tumor necrotic factor (TNF) alpha blockers (TNF-α) may reduce treatment resistance and the infusion reaction of IVIG after treatment initiation; further research is, however, needed. 28 Subcutaneous etanercept with IVIG for acute KD was studied in a randomized controlled trial.…”