Efficacy of the Delayed Use of Low-dose Aspirin in Intravenous Immunoglobulin Therapy for Acute-phase Kawasaki Disease

Toshimasa Nakada

doi:10.24018/ejmed.2021.3.1.691

Abstract

The mainstay of current standard therapy for acute-phase Kawasaki disease (KD) is intravenous immunoglobulin (IVIG) therapy at 2 g/kg. However, the efficacy of combining medium- or high-dose aspirin with IVIG therapy at 2 g/kg has not been fully investigated. Some studies suggested that aspirin may inhibit coronary artery lesion (CAL) prevention in IVIG therapy and that the delayed use of aspirin in IVIG therapy may be beneficial for the suppression of CALs and prevention of coronary artery stenosis in patients with KD. The efficacy of the delayed use of low-dose aspirin in IVIG therapy for acute-phase KD remains unclear. Therefore, this retrospective study aimed to assess the efficacy of the delayed use of low-dose aspirin, when combined with IVIG therapy for acute-phase KD. Data were obtained from 193 KD patients who underwent acute-phase treatment from January 2009 to October 2020 and IVIG therapy at 2 g/kg with the delayed use of aspirin/flurbiprofen. The patients were divided into three groups: (1) low-dose group, in which 40 patients received low-dose aspirin (5 mg/kg/day); (2) medium-dose group, in which 90 patients received medium-dose aspirin (30 mg/kg/day); and (3) flurbiprofen group, in which 63 patients received flurbiprofen (3–5 mg/kg/day). KD patients with liver damage or those present during influenza season underwent flurbiprofen therapy between January 2009 and November 2017. All patients except one received low-dose aspirin after December 2017. The serum albumin level (median 3.40 vs. 3.30 g/dL, P = 0.026) and Egami score (median 1.0 vs. 2.0, P < 0.001) before the initial treatment were significantly different between the medium-dose group and the flurbiprofen group. The rates of initial IVIG therapy resistance (25.0% vs. 18.9% vs. 25.4%, P = 0.790), rescue therapy (17.5% vs. 8.9% vs. 17.5%, P = 0.721), and CALs (5.0% vs. 0.0% vs. 4.8%, P = 0.713) were similar among the low-dose, medium-dose, and flurbiprofen groups. Overall, the efficacy of the delayed use of low-dose aspirin was similar to that of the delayed use of medium-dose aspirin/flurbiprofen in IVIG therapy for acute-phase KD.

Highlights

Kawasaki disease (KD) is a form of acute febrile systemic vasculitis that primarily affects children younger than 5 years [1]
The main finding of this study was that the rates of initial intravenous immunoglobulin (IVIG) therapy resistance, rescue therapy, and coronary artery lesion (CAL) were similar among the low-dose, medium-dose, and flurbiprofen groups (Tables I, II, III, and IV)
Current evidence based on a meta-analysis demonstrated that treatment combined with low-dose aspirin compared with high-dose aspirin (≥ 30 mg/kg/day) for the acute-phase treatment of KD showed no significant difference in the incidence of CAL, the risk of IVIG therapy resistance, or the length of fever or hospital stay [14]

Summary

Introduction

Kawasaki disease (KD) is a form of acute febrile systemic vasculitis that primarily affects children younger than 5 years [1]. The efficacy of combining medium- or high-dose aspirin with IVIG therapy at 2 g/kg has not been fully investigated [4]. A randomized controlled trial on the effectiveness of IVIG monotherapy versus IVIG therapy combined with high-dose aspirin in the acute KD stage is ongoing [5]. Some studies suggested that aspirin may inhibit CAL prevention in IVIG therapy and that the delayed use of aspirin (DUA) for IVIG therapy may be beneficial for the suppression of CALs and prevention of coronary artery stenosis in patients with KD [6]–[9]. A recent study showed favorable medium-term outcomes of CALs in KD patients who underwent IVIG therapy at 2 g/kg with DUA [10]

Methods

Results

Conclusion