Comparison of Risk of Recrudescent Fever in Children With Kawasaki Disease Treated With Intravenous Immunoglobulin and Low-Dose vs High-Dose Aspirin

Question Is initial treatment with low-dose aspirin, along with intravenous immunoglobulin, for children with Kawasaki disease associated with an increase in recrudescent fever? Findings In this cohort study of 260 children with Kawasaki disease, initial treatment with low-dose aspirin was not associated with higher odds of fever recrudescence compared with children treated with high-dose aspirin. In addition, no association was identified between low-dose aspirin and coronary artery abnormality or length of stay. Meaning Given the potential benefits and similar outcomes, further investigation into the use of low-dose aspirin in conjunction with intravenous immunoglobulin for the initial treatment of children with Kawasaki disease is warranted. Importance Timely initiation of intravenous immunoglobulin plus aspirin is necessary for decreasing the risk of recrudescent fever and coronary artery abnormalities in children with Kawasaki disease (KD). The optimal dose of aspirin, however, remains unclear. Objective To evaluate whether initial treatment with low-dose compared with high-dose aspirin in children with KD is associated with an increase in fever recrudescence. Design, Setting, and Participants A retrospective cohort study of 260 children with KD at Riley Hospital for Children, Indianapolis, Indiana, between January 1, 2007, and December 31, 2018, was conducted. Children aged 0 to 18 years with a first episode of KD, identified by International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes treated within 10 days of symptom onset with high-dose intravenous immunoglobulin plus aspirin were eligible. Patients who received an alternative diagnosis, experienced a second episode of KD, did not receive intravenous immunoglobulin plus aspirin for initial treatment, were not treated within 10 days of symptoms, or had incomplete records were excluded. Exposures High-dose (>= 10 mg/kg/d) or low-dose (<10 mg/kg/d) aspirin therapy. Main Outcomes and Measures The primary outcome was recrudescent fever necessitating retreatment of KD. The secondary outcomes were coronary artery abnormalities and hospital length of stay. Results Among the 260 patients included, the median (interquartile range) age was 2.5 (1.6-4.3) years, 103 (39.6%) were girls, 166 (63.8%) were non-Hispanic white, 57 (21.9%) were African American, 22 (8.5%) were Asian, 11 (4.2%) were Hispanic, and 4 (1.5%) were of unknown race/ethnicity. One hundred-forty-two patients (54.6%) were treated with low-dose aspirin. There was no association between recrudescent fever and aspirin dose, with 39 children (27.5%) having recrudescent fever in the low-dose group compared with 26 children (22.0%) in the high-dose group (odds ratio [OR], 1.34; 95% CI, 0.76-2.37; P = .31), with similar results after adjusting for potential confounding variables (OR, 1.63; 95% CI, 0.89-2.97; P = .11). In a subset analysis of 167 children with complete KD, however, there was nearly a 2-fold difference in the odds of recrudescent fever with low-dose aspirin (OR, 1.87; 95% CI, 0.82-4.23; P = .14), although this difference did not reach statistical significance. In addition, no association was identified between treatment group and coronary artery abnormalities (low-dose, 7.4% vs high-dose, 9.4%; OR, 0.86; 95% CI, 0.48-1.55; P = .62) or median (interquartile range) length of stay (3 [3-5] days for both groups; P = .27). Conclusions and Relevance In this study, low-dose aspirin for the initial treatment of children with KD was not associated with fever recrudescence or coronary artery abnormalities. Given the potential benefits, further study of low-dose aspirin to detect potentially clinically relevant outcome differences is warranted to inform treatment decisions and guideline development. This cohort study examines the incidence of recrudescent fever during use of low-dose vs high-dose aspirin in conjunction with intravenous immunoglobin in children with Kawasaki disease.