Prospective open-label trial of etanercept as adjunctive therapy for kawasaki disease

Abstract

Objective: To determine the safety and pharmacokinetics of etanercept (Amgen, Thousand Oaks, California) a tumor necrosis factor-α receptor blocker, in children with acute Kawasaki disease (KD). Standard therapy of acute KD includes intravenous immunoglobulin (IVIG) and high-dose aspirin, but a substantial number of patients are refractory and require additional treatment. Tumor necrosis factor-α levels are elevated in children with KD, suggesting a role for etanercept in treatment.

Study design: We performed a prospective open-label trial of etanercept in patients with KD (age range, 6 months-5 years; n = 17) meeting clinical criteria and with fever ≤ 10 days. All received IVIG and high-dose aspirin. They received etanercept immediately after IVIG infusion and then weekly two times. For the initial safety evaluation, the first 5 patients received 0.4 mg/kg/dose. Subsequent subjects received 0.8 mg/kg/dose.

Results: Fifteen patients completed the study. The pharmacokinetics were similar to that in older children in published series. No serious adverse events related to etanercept occurred. No patient demonstrated prolonged or recrudescent fever requiring re-treatment with IVIG. No patient showed an increase in coronary artery diameter or new coronary artery dilation/cardiac dysfunction.

Conclusion: Etanercept appears to be safe and well tolerated in children with KD. The data support performance of a placebo-controlled trial.

Figure 1

Left ventricular shortening fraction (median and quartile, n = 15). All patients had a normal SF at baseline. There was no significant change in the SF over the study time period.

Figure 2

Maximal coronary artery z score median and quartile data for all patients (n = 15). No new coronary artery dilation/aneurysms developed during the study time period. The individual dots represent the patient who had a RCA aneurysm and a dilated LAD.

Figure 3

Etanercept serum concentrations over time for 0.4mg/kg dosing. Each symbol represents a single patient with KD. The dotted and dashed lines are superimposed simulations of the mean from the JIA cohort females and males respectively. The solid lines represent the 5^th and 95^th percentiles.

Figure 4

Etanercept serum concentrations over time for 0.8mg/kg dosing. Each symbol represents a single patient with KD. Open symbols and (+) are patients < 2 years of age. The dotted and dashed lines are superimposed simulations of the mean from the JIA cohort females and males at 0.8mg/kg/dose once weekly. The solid curves represent the 5^th and 95^th percentile for the JIA cohort.