TOPLINE:

Adding prednisolone to standard intravenous immunoglobulin (IVIG) plus aspirin treatment did not reduce the incidence of coronary artery lesions at 1 month after the illness onset among children with Kawasaki disease, compared with standard treatment alone.

METHODOLOGY:

• Researchers conducted a phase 3 randomized controlled trial at 28 sites across China (2020-2024), enrolling 3208 children aged 1 month or older (mean age, 2.7 years) with Kawasaki disease newly diagnosed within 10 days after fever onset and who had not received IVIG treatment.
• Participants were randomly assigned to receive either standard treatment alone (IVIG, 2 g/kg of body weight; maximum dose, 60 g; and 30 mg/kg/d oral aspirin divided into three doses, with the aspirin dose reduced after the resolution of fever and normalization of C-reactive protein [CRP] level and maintained for ≥ 6 weeks; n = 1604) or prednisolone (2 mg/kg/d; maximum dose, 60 mg; tapered over 15 days after the normalization of CRP level) plus standard treatment (n = 1604).
• Assessments included two-dimensional echocardiography at enrollment and at multiple timepoints up to 12 months after illness onset, along with body temperature measurement, laboratory tests, and safety evaluations.
• The primary outcome was the occurrence of coronary artery lesions (defined as a Z score ≥ 2 in any coronary segment according to the 2017 American Heart Association criteria) at 1 month after illness onset.
• Secondary outcomes included the occurrence of coronary artery lesions at 2 weeks and 3 months, receipt of rescue therapy, duration of fever after IVIG initiation, and change in the CRP level at 72 hours after IVIG completion.

TAKEAWAY:

• At 1 month after illness onset, coronary artery lesions were detected in 16.0% of participants receiving prednisolone plus standard treatment and in 13.8% of those receiving standard treatment alone (P = .31). Among participants with resistance to IVIG, the incidence of lesions at 1 month was 45.2% with prednisolone plus standard treatment vs 25.6% with standard treatment alone (adjusted risk difference, 13.5 percentage points; 95% CI, 2.7-24.3).
• Rescue therapy was required in 4.6% of participants on prednisolone plus standard treatment compared with 10.1% of those on standard treatment alone (risk ratio, 0.45; 95% CI, 0.34-0.59), and the median duration of fever was 8.4 vs 13.2 hours in the respective groups (hazard ratio, 0.67; 95% CI, 0.61-0.73).
• At 72 hours after IVIG completion, the reduction in CRP was greater in the prednisolone plus standard treatment group (-67.5 vs -59.8 mg/L; mean difference, -7.6 mg/L; 95% CI, -10.9 to -4.3).

IN PRACTICE:

“The work of Lin et al. aligns with medical society recommendations in the United States and Japan: Treatment with adjunctive glucocorticoids is not indicated in unselected patients with Kawasaki disease. The trial also suggests that although glucocorticoid therapy improves systemic inflammation, it remains imperfect at controlling inflammation in the coronary arterial wall. Because glucocorticoids can mask fever, which is often used as an indicator of disease activity, frequent echocardiographic surveillance is critical for patients receiving intensified regimens,” experts wrote in an accompanying editorial.

SOURCE:

The study was led by Siyuan Lin, MD, Pediatric Heart Center, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China. It was published online on April 15, 2026, in The New England Journal of Medicine.

LIMITATIONS:

Trial enrollment during the pandemic fell below expectations, with an increased dropout rate. The primary analysis included participants who did not meet the eligibility criteria. Subgroup and exploratory analyses were underpowered, and follow-up is ongoing, with the current analysis lacking 6-month and 1-year data.

DISCLOSURES:

The study received support from grants provided by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences and the National Natural Science Foundation of China. The authors did not have any relevant financial disclosures.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.