THE USE OF INTERLEUKIN 1 RECEPTOR ANTAGONIST (ANAKINRA) IN KAWASAKI DISEASE: A RETROSPECTIVE CASES SERIES

Abstract

Introduction: Persistent fever and inflammation after infusion of 2g/kg of IVIG, the standard treatment of KD represents a high-risk situation for coronary aneurysms in Kawasaki disease. Identifying patients at risk for IVIG resistance is difficult outside the Asian population, and there remains a critical unmet need to identify an anti-inflammatory treatment that is efficacious in all KD patients. Recent evidence from studies in animals and humans suggest a critical role for interleukin-1 (IL-1) α and β in the pathogenesis of KD. Objectives: To identify the clinical characteristics, reasons for use and response to treatment with anakinra in a retrospective series of patients with Kawasaki Disease (KD). Methods: A retrospective chart review of patients treated with anakinra for KD diagnosed according to the AHA criteria. We compared clinical, biological and echocardiographic characteristics of KD before and after anakinra use. We analysed reasons for use of anakinra, and compared treatment regimens used in 7 European KD referral centres. Results: Eight boys and 3 girls with treatment-refractory KD, aged 4 months to 9 years old, received at least 2 different KD treatments prior to anakinra, which was given on mean at 25 days after disease onset (8 to 87 days). The main reasons for use of anakinra were clinical and biological inflammation, progression of coronary dilatations, and severe myocarditis with cardiac failure. Doses of anakinra ranged from 2 to 8 mg/kg and duration varied from 6 to 81 days. On anakinra treatment, fever disappeared within hours (<24 h) in 3 patients, and within 2 and 6 days in two patients respectively. Six others patients were not febrile at onset of anakinra. In addition, CRP levels fell two to three fold within 48 hours in 7/9 evaluable patients. In terms of its effect on coronary artery dilatation, Z scores decreased in 10/11 patients and increased in one who died suddenly of pericardial hemorrhage. Conclusion: Anakinra used late in the disease course led to a rapid and sustained improvement in clinical and biological inflammation. However, our retrospective analysis did show neither a striking nor a rapid decrease of coronary dilatations and we cannot determine if anakinra itself had an effect on coronary artery dimensions. More robust data will be available soon from the two Phase II ongoing trials, KAWAKINRA using anakinra treatment early after one failure of IVIG treatment (European Clinical Trials no. 2014-002715-41) and ANAKID (ClinicalTrials.gov identifier: NCT02179853), focused on patients with coronary giant aneurysms.