Efficacy and Limitation of Infliximab Treatment for Children with Kawasaki Disease Intractable to Intravenous Immunoglobulin Therapy: Report of an Open-label Case Series

Abstract

Objective.Kawasaki disease (KD) is an acute febrile disease in infants and young children. Five percent to 8% of cases will be complicated with coronary dilatation or aneurysm, although introduction of high-dose intravenous immunoglobulin (IVIG) therapy has provided remarkable results for reducing the frequency of cardiac involvement. We describe the results of an open-label trial of infliximab, an anti-tumor necrosis factor-α monoclonal antibody, for suppressing the progression of coronary artery lesions in cases of KD refractory to extensive IVIG therapy. Plasma exchange (PE) was available as a rescue therapy for patients refractory to infliximab.Methods.Twenty eligible patients fulfilled the diagnostic criteria for KD, and were primarily treated with IVIG up to 4 g/kg. “Refractory to IVIG” was defined as persisting or reemerging fever > 38°C and positive fractional changes of C-reactive protein, white blood cell counts, or neutrophil counts 48 hours after IVIG infusion. These cases were treated with infliximab, 5 mg/kg, which should begin within 10 days of disease onset. PE for patients refractory to infliximab was performed with 5% albumin.Results.There was rapid improvement of inflammatory symptoms as well as normalization of the inflammatory markers. Sequential examination by echocardiography up to disease Day 30 revealed that the inflamed and mildly dilated coronary artery at the beginning of the study regressed to normal size in the convalescent phase. Two out of 20 patients showed incomplete improvement of inflammatory symptoms after infliximab treatment, and were provided with PE therapy, with no complications.Conclusion.Eighteen of 20 patients were effectively treated with infliximab, and 2 cases were effectively treated with PE to prevent progression to coronary artery lesions. No adverse event such as anaphylactoid reaction, heart failure, severe infectious diseases, or tuberculosis was observed in this trial.