Infliximab Treatment for Refractory Kawasaki Disease in Korean Children

Abstract

Background and ObjectivesThis was a multicenter study to evaluate the usefulness of the tumor necrosis factor-alpha (TNF-α) blocker infliximab for treatment of Korean pediatric patients with refractory Kawasaki disease (KD).Subjects and MethodsData from 16 patients throughout Korea who were diagnosed with refractory KD and received infliximab were collected retrospectively.ResultsComplete response to therapy with cessation of fever occurred in 13 of 16 patients. C-reactive protein (CRP) concentrations decreased following infliximab infusion in all 14 patients in whom it was measured before and after treatment. There were no infusion reactions or complications associated with infliximab except in 1 case with acute hepatitis occurring during treatment followed by calculous cholecystitis 4 months later. Fifteen patients had coronary artery (CA) abnormalities before infliximab therapy. Three had transient mild dilatation and 9 had CA aneurysms, with subsequent normalization in 4 patients, persistent mild dilatation in 3, persistent aneurysm in 2, and there were 3 cases (2 with CA aneurysm, 1 with mild CA dilatation) without follow-up echocardiography.ConclusionThe results of this study suggest that infliximab may be useful in the treatment of refractory KD, and it appears that there is no significant further progression of CA lesions developing after infliximab treatment. Multicenter trials with larger numbers of patients and long-term follow-up are necessary to assess the clinical efficacy and safety of infliximab in refractory KD.

Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial

“…28 Since then, infl iximab has been used worldwide for treatment-resistant Kawasaki disease. 7,[29][30][31][32] These anecdotal reports of one to 20 patients all indicated a benefi t with a decrease in clinical signs including fever and markers of infl ammation. An analysis of the Paediatric Health Information System database from 2001 to 2006 showed that 14 of the 27 participating hospitals had administered infl iximab to 48 patients for treatmentresistant Kawasaki disease.…”

“…We identifi ed several reports worldwide about the use of infl iximab for treatment-resistant Kawasaki disease. 7,[28][29][30][31][32][33] A phase 1 trial of second intravenous immunoglobulin versus infl iximab for intravenous immunoglobulin-resistant Kawasaki disease showed that infl iximab was safe and well tolerated. 8 Subsequently, a retrospective review of intravenous immunoglobulin-resistant patients treated with either a second intravenous immunoglobulin or infl iximab showed that patients treated with infl iximab had fewer days of fever (median 8 vs 10 days, p=0·028) and shorter lengths of hospitalisation (median 5·5 vs 6 days, p=0·04) than those treated with a second intravenous immunoglobulin.…”

Increased Percentages of Tumor Necrosis Factor-α+/Interferon-T+Lymphocytes and Calprotectin+/Tumor Necrosis Factor-A+ Monocytes in Patients with Acute Kawasaki Disease

“…Moreover, some studies reported the increased production of TNFa, and in particular its role in the inflammation of arteries, as immunological marker of acute phase of KD. In fact, infliximab and etanercept, monoclonal antibodies blocking the biological activity of TNF-u, were used for refractory KD patients and were reported to be effective and safe (4,5). An efficient therapy, based on intravenous infusion of high doses of immunoglobulins (lVIG), has been found to effectively reduce the inflammation and the incidence of coronary artery lesions (6).…”

Use of Anti TNF-α Therapy in Systemic Vasculitis

“…No complications or side effects have occurred in all 15 patients. Table 6 shows a summary of studies that addressed the use of anti TNF-α agents in patients with Kawasaki disease [57][58][59][60][61][62][63]. …”