Etanercept With IVIg for Acute Kawasaki Disease: A Randomized Controlled Trial

• Published in: Pediatrics (Evanston) Vol. 143; no. 6; p. 1
• Main Authors: Portman, Michael A, Dahdah, Nagib S, Slee, April, Olson, Aaron K, Choueiter, Nadine F, Soriano, Brian D, Buddhe, Sujatha, Altman, Carolyn A
• Format: Journal Article
• Language: English
• Published: United States American Academy of Pediatrics 01-06-2019
• Subjects: Acute Disease; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Care and treatment; Child, Preschool; Coronary artery; Diagnosis; Dilation; Double-Blind Method; Drug Resistance - drug effects; Drug Resistance - physiology; Drug Therapy, Combination; Etanercept; Etanercept - administration & dosage; Female; Humans; Immunoglobulins; Immunoglobulins, Intravenous - administration & dosage; Infant; Intravenous administration; Kawasaki disease; Kawasaki syndrome; Male; Mucocutaneous lymph node syndrome; Mucocutaneous Lymph Node Syndrome - diagnostic imaging; Mucocutaneous Lymph Node Syndrome - drug therapy; Pediatrics; Tumor necrosis factor-α
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.2018-3675

Patients with Kawasaki disease can develop life-altering coronary arterial abnormalities, particularly in those resistant to intravenous immunoglobulin (IVIg) therapy. We tested the tumor necrosis factor α receptor antagonist etanercept for reducing both IVIg resistance and coronary artery (CA) disease progression.
In a double-blind multicenter trial, patients with Kawasaki disease received either etanercept (0.8 mg/kg;
= 100) or placebo (
= 101) subcutaneously starting immediately after IVIg infusion. IVIg resistance was the primary outcome with prespecified subgroup analyses according to age, sex, and race. Secondary outcomes included echocardiographic CA measures within subgroups defined by coronary dilation (
score >2.5) at baseline. We used generalized estimating equations to analyze
score change and a prespecified algorithm for change in absolute diameters.
IVIg resistance occurred in 22% (placebo) and 13% (etanercept) of patients (
= .10). Etanercept reduced IVIg resistance in patients >1 year of age (
= .03). In the entire population, 46 (23%) had a coronary
score >2.5 at baseline. Etanercept reduced coronary
score change in those with and without baseline dilation (
= .04 and
= .001); no improvement occurred in the analogous placebo groups. Etanercept (
= 22) reduced dilation progression compared with placebo (
= 24) by algorithm in those with baseline dilation (
= .03). No difference in the safety profile occurred between etanercept and placebo.
Etanercept showed no significant benefit in IVIg resistance in the entire population. However, preplanned analyses showed benefit in patients >1 year. Importantly, etanercept appeared to ameliorate CA dilation, particularly in patients with baseline abnormalities.