Low‐ versus high‐concentration intravenous immunoglobulin for children with Kawasaki disease in the acute phase

Abstract

Purpose: Few studies have compared the effects of low-concentration (5%) and high-concentration (10%) intravenous immunoglobulin (IVIG) preparations for patients with Kawasaki disease (KD) in the acute phase. The purpose of this study was to compare outcomes between low-and high-concentration IVIG preparations in children with KD, using a national inpatient database in Japan.Method: We used the Diagnostic Procedure Combination database to identify patients with KD treated with IVIG from April 2012 to March 2020. We identi ed those receiving high-and low-concentration IVIG preparations as an initial treatment. The outcomes included the proportions of patients with coronary artery abnormalities (CAAs) and IVIG resistance, length of stay, and medical costs. Propensity scorematched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to con rm the results.Result: We identi ed 48,046 patients with KD and created 4:1 propensity score-matched pairs between the low-and high-concentration IVIG groups. There was a signi cant difference in the percentage with IVIG resistance between the two groups (20.6% vs 24.1%; risk difference, 3.5% [95% con dence interval, 2.3-4.7]; p < 0.001). However, there was no signi cant difference in CAAs (1.6% vs 1.6%; risk difference, 0.013% [95% con dence interval, −0.34 to 0.37]; p = 0.953). The instrumental variable analyses showed similar results.Conclusions: The proportion of CAAs did not differ signi cantly between those receiving low-and highconcentration IVIG. To con rm the results of this study, prospective studies adjusting for duration of IVIG administration and duration of observation are needed. BackgroundWhat is Known:-For treatments of Kawasaki Disease in acute phase, intravenous immunoglobulin (IVIG) has been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. There are two types of IVIG preparations, low-concentration (5%) IVIG and high-concentration (10%) IVIG. However, few studies have performed comparisons to determine which preparation of IVIG is superior.What is New:-The present ndings suggest that the proportion of coronary artery abnormalities did not differ signi cantly between those receiving low-and high-concentration IVIG.

Comparative effectiveness of two intravenous immunoglobulin products in children with Kawasaki disease, a nationwide cohort study

“…Thus, the difference in infusion time by different concentration cannot explain the phenomenon we observed in this study. A small retrospective cohort and another nationwide inpatient database study in Japan observed no significant difference between 5 and 10% IVIG for the treatment of patients with acute-phase KD 28 , 29 . Based on aforementioned, we therefore infer that the difference in concentration of TBSF and Privigen is not responsible for clinical differences.…”

Impact of Kawasaki disease on juvenile idiopathic arthritis in real-world patients: A population-based cohort study

“…As KD progresses, C-reactive protein levels increase in tandem with increases in IL-1β and IL-6 Levels ( 35 , 36 ). In 1991, Newburger proposed intravenous immunoglobulin therapy, which has become the conventional treatment for KD ( 37 , 38 ). Although the mechanism behind this treatment remains unclear, intravenous immunoglobulin is thought to reduce the levels of inflammatory cytokines and thus achieve their balance.…”

High-Concentration Intravenous Immunoglobulin May Influence the Course of Fever and Rate of Reported Treatment Resistance in Children With Kawasaki Disease: A Single-Center Retrospective Analysis

“…A few studies have reported on the association between IVIG concentration and IVIG resistance in patients with KD [ 20 – 22 ]. Oda et al reported that the frequencies of adverse reactions and IVIG resistance were comparable between patients with KD who received 5% IVIG and those who received 10% IVIG and that fever duration after IVIG infusion was significantly shorter in patients who received 10% IVIG than in those who received 5% IVIG [ 21 ].…”

“…Oda et al reported that the frequencies of adverse reactions and IVIG resistance were comparable between patients with KD who received 5% IVIG and those who received 10% IVIG and that fever duration after IVIG infusion was significantly shorter in patients who received 10% IVIG than in those who received 5% IVIG [ 21 ]. However, a recent nationwide Japanese study including a larger number of patients with KD reported a significantly higher IVIG resistance rate without an increase in CAAs in patients who received 10% IVIG than in those who received 5% IVIG [ 22 ]. In Canadian children, a higher IVIG resistance rate was reported in patients who received 10% IVIG compared with those who received 5% IVIG [ 20 ].…”

“…This can shorten the timeframe required to determine IVIG resistance after IVIG infusion. Therefore, the 2020 Japanese KD guideline changed the time for defining IVIG resistance from 24 hours to 24–36 hours after the end of IVIG infusion based on the results of the above-mentioned nationwide study [ 22 , 26 ]. However, the AHA 2017 guideline had already recommended defining IVIG resistance ≥36 hours after the end of IVIG infusion [ 2 ], and this study adopted the AHA guideline.…”