Infliximab versus second intravenous immunoglobulin for treatment of resistant Kawasaki disease in the USA (KIDCARE): a randomised, multicentre comparative effectiveness trial

Abstract

Background Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10-20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease.Methods In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8-12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244.

Epidemiological and Clinical Features of Kawasaki Disease During the COVID-19 Pandemic in the United States

“…Date of onset was defined as the first day of fever and was reported monthly for all patients from 28 institutions participating in the KIDCARE trial. 9 The institutional review board (IRB) at the University of California, San Diego (UCSD; central IRB for trial) and participating sites approved the study. A waiver of informed consent was granted for collection of dates of KD onset because they are not protected health information.…”

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease

“…However, as a conditional recommendation, glucocorticoids are a reasonable alternative (e.g., starting at 2 mg/kg/day and tapering over 15 days or a single dose of 20–30 mg/kg). Repeated doses of IVIG may put patients at risk of hemolytic anemia, and the results of ongoing studies may alter this recommendation in the future (45–47). In patients with risk factors for hemolytic anemia with IVIG, such as non–type O blood groups, alternative therapies, such as glucocorticoids or nonglucocorticoid immunomodulatory therapy, should be considered (45,48).…”

Infliximab as a second‐line therapy for children with refractory Kawasaki disease: A systematic review and meta‐analysis of randomized controlled trials

“…Youn (2016) reported that the median duration of fever after completion of the first treatment was shorter in the infliximab group compared to the IVIG group (6 hours, IQR 2‐24 hours in the infliximab group and 17 hours, IQR 4‐62.5 hours in the IVIG group; P = .044) 30 . Burns (2021) reported that the mean duration of fever from enrolment was shorter in the infliximab group compared to the IVIG group (infliximab group 1.5 days [SD 1.4], IVIG group 2.5 days [SD 2.5]; P = .014) 31 …”