High-Dose IVIG With Glucocorticoids Shown to Benefit Patients With Kawasaki Disease at High Risk For IVIG Resistance

In children with Kawasaki disease (KD) who exhibited 3 or more risk factors for intravenous immunoglobulin (IVIG) resistance, initial treatment with high-dose IVIG, aspirin, and glucocorticoids effectively reduced fever duration, length of hospital stay, and incidence of coronary artery lesions (CALs) with a correspondingly positive safety profile, according to results published in Pediatric Cardiology.¹

IVIG is a standard care option for Kawasaki disease, but some patients can be resistant to treatment. | Image credit: © Felipe Caparrós | stock.adobe.com

Standard initial treatment of acute KD consists of high-dose IVIG and oral aspirin, which has successfully decreased CAL incidence in patients with KD. Despite these evident improvements in outcome, IVIG resistance can lead to some children being at higher risk of developing persistent CALs.¹

Non-response to IVIG is associated with multiple clinical factors, including white blood cell count, platelet count, serum ferritin, interleukin-6, male sex, and others. Incidence of IVIG non-responsiveness ranges from 7.5% to 26.8% and can lead to increased care needs for patients such as retreatments, prolonged hospitalization, and increased health care costs, while heightening the risk of CALs.²

Previously conducted trials have evaluated the efficacy of the addition of glucocorticoids to the IVIG-aspirin combination for initial treatments. Green et al, in a literature review first published in 2017 and updated in 2022, found that steroid use in the acute phase of KD was associated with reduced CAL incidence, a reduction in inflammatory markers, and shorter hospital stay.³

Therefore, the investigators of the current study sought to evaluate the clinical benefits of adding glucocorticoids to an initial treatment of IVIG and aspirin in children with KD. The trial focused on those most at risk for IVIG non-response. Resistance to IVIG was defined as persistent fever ≥ 38°C 48 hours after IVIG (2 g/kg) treatment within 10 days of KD onset or fever recurrence, accompanied by major KD symptoms.¹

A total of 236 IVIG-sensitive cases and 38 IVIG-resistant cases were gathered, with 26 cases in the observation cohort. Following treatment, those resistant to IVIG indicated higher rates of CALs compared with the IVIG-sensitive group at all post-treatment intervals. Prior to treatment, the observation group had higher CAL incidence than the IVIG-sensitive group.¹

Furthermore, the proportion of patients with ≥ 3 high-risk factors in the IVIG resistance group was deemed to be much higher than that of the IVIG-sensitive group. This was also the case in the observation group; however, no statistical difference in patients with ≥ 3 high-risk factors between the IVIG-resistant group and the observation group were observed.¹

In both the IVIG-sensitive and observational study groups, patients experienced significantly shorter fever resolution times and duration of hospital stays. These results align with those found by Green et al in their literature review, reaffirming the efficacy of glucocorticoids in patients with KD who have multiple risk factors for IVIG resistance.^1,3

This is especially notable given the more severe inflammatory reaction present in patients with KD who are IVIG-resistant than those who are IVIG-sensitive. Importantly, the treatment combination led to clinical improvement and CAL reduction in patients with KD without adverse effects related to glucocorticoids, a positive indication of safety.¹

Some trial limitations were noted by the study authors. These included the single-center, retrospective nature of the trial, in combination with the small number of patients. Continuing, the observation indicators of risk factors for IVIG-resistance were limited to inflammatory and biochemical indicators, which are not specific. They noted that the study results should be verified further in different patients to account for these limitations.¹

REFERENCES

1. Wang X, Shi X, Guo X, et al. Effectiveness of initial corticosteroid treatment in Kawasaki disease children suspected to be IVIG resistant. Pediatr Cardiol. 2024. doi:10.1007/s00246-024-03657-9

2. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927-e999. doi:10.1161/CIR.0000000000000484

3. Green J, Wardle AJ, Tulloh RMR, et al. Corticosteroids for the treatment of Kawasaki disease in children. Cochrane. 2022;5:CD011188. doi:10.1002/14651858.CD011188.pub3