番茄社区

Combining corticosteroids and intravenous immunoglobulin (IVIG) for high-risk children with Kawasaki disease was associated with much lower risk of coronary artery abnormalities, Japanese data showed.

Coronary artery dilation, aneurysm, and other abnormalities occurred in a median 4.6% of children who got the combination regimen versus 8.8% of those who got IVIG alone (RR 0.53, 95% CI 0.41-0.67), found Ryusuke Ae, MD, PhD, of the CDC's National Center for Emerging and Zoonotic Infectious Diseases in Atlanta, and colleagues.

Treatment failure, marked by recurrent or persistent fever at least 24-hours after IVIG, occurred 35% less often with the combination (median 14.1% vs 21.7%), thus reducing the need to administer secondary treatment, the group reported in the .

While the observational study couldn't directly say that the benefit was from the addition of primary corticosteroids, analyses controlling for unmeasured confounding supported that conclusion, the researchers noted.

The data came from nationwide surveys of Kawasaki disease treatment at hospitals in Japan, "where combination treatment (corticosteroids added to initial standard intravenous immunoglobulin treatment) has become commonly used for patients at high risk," they noted.

This data replicated findings from the 2011 RAISE randomized controlled trial in Japanese high-risk Kawasaki disease patients showing an 87% relative reduction in coronary artery abnormalities with primary combination treatment.

However, randomized trials from North America haven't corroborated the benefit with corticosteroid pulse treatment, despite some favoring better outcomes, commented Kevin Friedman, MD, of Boston Children's Hospital and a member of the American Heart Association's Young Hearts Council and its Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee.

Part of the problem, he told 番茄社区, is that "the Japanese high risk scoring system does not work in U.S. children to identify high risk, so it is unclear how well these findings apply outside of Japan."

Kawasaki disease has risen to national attention with the outbreak of a multisystem inflammatory syndrome in children (MIS-C) linked with COVID-19. While MIS-C differs in a number of ways from traditional Kawasaki disease -- such as occurring at older ages -- a proportion of cases have met the traditional Kawasaki disease criteria after SARS-CoV-2 exposure as well.

As to whether the findings have any implication for MIS-C, Friedman noted that both corticosteroids and IVIG are used for these patients, although it's "very hard to know if both are needed for some patients, all patients, or if other therapies (perhaps anakinra [Kineret]) would be better. I don't think this study informs much on MIS-C, unfortunately."

Ae's group identified 13,481 eligible Kawasaki disease patients in the 2009–2010 Japanese national survey and 20,460 in the 2015–2016 survey.

Combination treatment rose in use between the two periods, while coronary artery abnormalities fell. Combination treatment was reported for 12.9% of Kawasaki disease patients in the more recent survey, with the corticosteroid typically given in multiple doses over a period of days rather than the pulse favored in U.S. practice.

To minimize selection bias and other confounders, the researchers narrowed the study population to patients that were treated at the same set of 115 hospitals with high combination therapy use (at least 20%) and then matched patients by age category, sex, recurrence status, and duration of illness at first dose of IVIG for a control group. Finally, the combination therapy group was rematched by those same categories for a final tally of 1,593 combination group patients and 1,593 controls that didn't get a primary corticosteroid. Bootstrapping with 1,000 iterations was also used to control for sampling bias in the logistic regression.

While those numbers made this the largest study to assess the effectiveness of primary corticosteroid with IVIG for Kawasaki disease, the researchers pointed to lack of specificity about the type, dose, and duration of corticosteroid use as a major limitation. Nor was there information on coronary artery Z scores or standardization or centralization of echocardiogram reading.

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