Routine Prednisolone Does Not Prevent Coronary Lesions in Kawasaki Disease

A large randomized trial shows that adding steroids to standard therapy does not protect the coronary arteries of unselected children.

For Doctors in a Hurry

The clinical benefit of adding adjunctive glucocorticoids to standard primary treatment for unselected patients with Kawasaki disease remains unclear.
Researchers conducted a multicenter, randomized, controlled trial assigning 3208 participants to receive either prednisolone plus standard treatment or standard treatment alone.
At one month, coronary-artery lesions affected 16.0 percent of the prednisolone group and 13.8 percent of controls (95% confidence interval, -1.0 to 3.4; P=0.31).
The authors concluded that adding prednisolone to standard primary therapy did not reduce the incidence of coronary-artery lesions.
Consequently, these findings do not support the routine addition of prednisolone to standard therapy for preventing coronary-artery lesions in Kawasaki disease.

The Ongoing Debate Over Steroids in Kawasaki Disease

Kawasaki disease is an acute systemic vasculitis of early childhood that carries a significant risk of long-term cardiac complications, primarily through the development of coronary artery aneurysms [1, 2]. While standard therapy with intravenous immunoglobulin and aspirin effectively reduces systemic inflammation, a notable subset of patients still develops coronary lesions, prompting a search for adjunctive treatments [3]. Corticosteroids are a mainstay for other vasculitides, but their role in the initial management of Kawasaki disease has remained highly controversial [4]. Although some data suggest that adding steroids might benefit patients with severe or high-risk disease, their utility as a routine primary therapy for all patients is unclear [5]. A large randomized trial now provides definitive evidence on whether upfront steroid therapy can protect the coronary arteries of unselected pediatric patients.

Testing Steroids in an Unselected Population

To evaluate the effect of adjunctive glucocorticoids in the primary treatment of Kawasaki disease, researchers conducted a multicenter, open-label, randomized, controlled trial in China. A total of 3208 participants with newly diagnosed Kawasaki disease underwent randomization. These children were assigned in a 1:1 ratio to receive either prednisolone plus standard treatment or standard treatment alone. Notably, a significant portion of the cohort already showed signs of cardiac involvement before the intervention began, as coronary-artery lesions were detected at baseline in 870 of 3184 participants (27.3%).

The primary outcome of the trial was the occurrence of coronary-artery lesions at 1 month after illness onset. The investigators also tracked several prespecified key secondary outcomes, including the receipt of rescue therapy, the duration of fever, the change in the C-reactive protein (CRP) level, and changes in coronary-artery z scores (a standardized echocardiographic measure of coronary artery dimensions adjusted for patient body surface area). The analyses for these secondary outcomes were not controlled for multiplicity (meaning the statistical tests were not adjusted for the increased risk of false-positive results that occurs when performing multiple comparisons). The trial was funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences and the National Natural Science Foundation of China (ClinicalTrials.gov number, NCT04078568).

Primary Outcome: No Protection for Coronary Arteries

The trial demonstrated that the addition of prednisolone to standard primary treatment for Kawasaki disease did not reduce the incidence of coronary-artery lesions at 1 month after illness onset. At the 1-month follow-up, coronary-artery lesions were detected in 16.0% of the participants receiving prednisolone plus standard treatment, compared to 13.8% of the participants receiving standard treatment alone. This yielded an adjusted risk difference of 1.1 percentage points (95% confidence interval, -1.0 to 3.4; P = 0.31), indicating no statistically significant benefit from the adjunctive steroid therapy. Furthermore, structural assessments showed that decreases in coronary-artery z scores were similar in the two groups, confirming that the routine use of upfront steroids does not offer superior structural cardiac protection for the average patient.

The lack of cardiovascular protection persisted during longer-term follow-up. At 3 months, the incidence of coronary-artery lesions was 12.6% with prednisolone plus standard therapy and 10.5% with standard treatment alone. The trajectory of existing vascular damage also remained unaffected by the intervention. Specifically, at 3 months, the percentage of participants with progression of coronary-artery lesions was 28.6% in the prednisolone group and 28.9% in the standard treatment alone group. The risk of severe complications was similarly unchanged, as the incidence of medium-to-giant coronary-artery aneurysms was 1.9% in the prednisolone group and 1.1% in the standard treatment alone group at the 3-month mark. For practicing pediatricians and cardiologists, these findings clearly establish that adding routine prednisolone to standard intravenous immunoglobulin therapy does not prevent the development or progression of coronary aneurysms in unselected children.

Systemic Symptom Relief Without Cardiac Benefit

Although adjunctive steroids failed to improve the primary cardiac endpoint, the secondary outcomes demonstrated that prednisolone effectively accelerated the resolution of acute systemic symptoms. Clinically, this was most evident in temperature control, as the median duration of fever was 8.4 hours in the prednisolone group and 13.2 hours in the standard treatment alone group. This faster defervescence was accompanied by a more rapid decline in systemic inflammation. Specifically, the reductions in the C-reactive protein level at 72 hours were 67.5 mg per liter in the prednisolone group and 59.8 mg per liter in the standard treatment alone group.

The accelerated clearance of systemic inflammation directly translated to a reduced need for additional medical interventions. Rescue therapy was used in 4.6% of the participants receiving prednisolone plus standard therapy, compared to a higher rate where rescue therapy was used in 10.1% of the participants receiving standard treatment alone. Importantly, this symptomatic benefit did not come at the cost of increased toxicity, because the overall incidence of adverse events did not differ significantly between the two groups. For clinicians managing acute Kawasaki disease, these results provide a clear directive. While prednisolone safely and rapidly reduces fever and inflammatory markers, its inability to prevent coronary artery aneurysms means that adjunctive steroids should likely be reserved for refractory cases or high-risk subgroups, rather than prescribed universally as a primary treatment.

Study Info

Randomized Trial of Adjunctive Prednisolone for Kawasaki Disease

Siyuan Lin, Yuanchen He, L He, Yiling Liu, et al.

Journal New England Journal of Medicine

Published April 15, 2026