Study Shows the Efficacy of Adding Corticosteroids to Initial Intravenous Immunoglobulin Therapy in the Prevention of Coronary Artery Abnormality Among Patients at High Risk for Kawasaki Disease

A recent study by Dr. Ryusuke Ae, published in the Journal of the American Heart Association, demonstrated the efficacy of combining the initial intravenous immunoglobulin (IVIG) treatment with multiple-dose corticosteroids in the prevention of coronary artery abnormalities in selected patients at high risk for Kawasaki disease. The study showed a reduction in coronary artery abnormalities and treatment failure after applying this treatment strategy.

Coronary artery abnormalities are known complications of Kawasaki disease (KD). The conventional standard treatment, IVIG and aspirin, has considerably reduced these complications. However, about 17% of patients with KD do not respond to IVIG treatment and will be at higher risk of developing complications. Interestingly, there are scoring systems to identify this category of non-responders. Recent studies done in Japan supported the efficacy of corticosteroids used in combination with the standard treatment in patients with predicted high risk for nonresponse to IVIG. However, the results of these studies still remain skeptical and limited by the small sample size. In this study, the investigators analyzed large-scale data from nationwide KD surveys in Japan to assess the efficacy of corticosteroid combination treatment in the prevention of complications among patients at high risk for KD.

This retrospective cohort study derived the data from 21st and 24th nationwide KD surveys in Japan. In these surveys, corticosteroid was added either as pulse or multiple-dose to the initial IVIG treatment. Hospitals that reported ≥ 20% of patients received combination treatment, were selected, and treatment and control groups were chosen via matching by age, gender, illness day at initial treatment, and KD recurrence. Matching and subsequent analyses were done 1000 times to reduce sampling and confounder biases. The outcomes of interest were coronary artery abnormalities (defined per the Japanese Ministry of Health) as well as initial treatment failure, defined as the development of recurrent or persistent fever (≥37.5℃) at least 24 hours after the end of the initial IVIG administration.

A total of 1593 patients with KD in the treatment group and 1593 controls were included in each analysis.  Corticosteroid combination treatment was associated with a risk reduction in the development of coronary artery abnormalities (47%; 95% Confidence Interval (CI):[ 33–59]) and treatment failure (35%; 95% CI:[25–44]) in patients at high risk for KD. The data from this study provide evidence for the efficacy of supplementing the standard therapy with multiple-dose corticosteroids. This may lead to a considerable reduction in the risk of developing complications in high-risk KD patients.

Finally, the results of this study should be interpreted in light of its limitations. First, the study did not include information on the type, dosage, and duration of corticosteroids. Second, the prevalence of coronary artery abnormalities may be underestimated. Third, the echocardiogram readers were not blinded to the treatment of participants that might have affected their clinical judgment and led to bias. Also, the study evaluated the outcomes of interest in a homogenous Japanese population that may affect the generalizability of the study. Future studies are warranted to further confirm the result of this study.