Open Label, Phase II Study with Anakinra in Intravenous Immunoglobulin-Resistant Kawasaki Disease

Authors : Kone-Paut, I., Tellier, S., Belot, A., Brochard, K., Guitton, C., Marie, I., Meinzer, U., Cherqaoui, B., Galeotti, C., Boukhedouni, N., Agostini, H., Arditi, M., Lambert, V., and Piedvache, C.

Publication: Arthritis Rheumatol.; September 2020

Affiliations: Division of Pediatric Rheumatology and CEREMAIA, Bicêtre Hospital, APHP, University of Paris sud Saclay, Le Kremlin-Bicêtre, France; Department of Pediatrics, Divisions of Nephrology, Rheumatology and Internal Medicine, University of Toulouse, Toulouse, France; Departments of Pediatrics, Division of Rheumatology, Dermatology and Nephrology, University of Lyon, Lyon, France; CIRI, INSERM U1111, ENS, Lyon, France Infectious and Immunologic Diseases Research Center, Departments of Biomedical Sciences and Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Division of Pediatric Cardiology, Institut Mutualiste Montsouris and Bicêtre Hospital, APHP, University of Paris Sud Saclay, Le Kremlin-Bicêtre, France; APHP, Paris Saclay, Clinical Research Unit Paris-Sud, Bicêtre Hospital, Le Kremlin-Bicêtre, France.

Abstract: OBJECTIVE: Determine the safety of blocking interleukin 1 in patients with KD that are unresponsive to IVIG. DESIGN: Patients with KD that failed to respond to one or more courses of 2g/kg of IVIG received anakinra by subcutaneous daily injections. Starting doses were 2mg/kg (4mg/kg in patients < or equal to 8 months and > or equal to 5 kg), which was increased up to 6mg/kg every 24h if temperature remained >38° C. Treatment duration was 14 days. The last visit was at day 45. Primary outcome was abatement of fever. Secondary measures included disease activity, coronary artery z score, and C reactive protein (CRP) level. RESULTS: 16 patients were included. 75% of patients in the intention-to-treat group and 87.5% in the per protocol group became afebrile within 48 hours of the last escalation dose of anakinra. Reduction of disease activity by 50% was reached by 93.3% (CI: 68.1; 99.8) of physician’s evaluations and by 100% (CI: 73.5; 100) of parent’s evaluations. CRP values normalized by day 30. At screening, 12/16 patients had coronary arteries z score max >2, and 10/16 a z score max >2.5. At day 45, 5/10 (50%, CI: 18.7; 81.3) and 6/12 patients (50%, CI: 21.1; 78.9) reached a coronary artery z score <2.5 and <2, respectively. Three patients had five serious adverse events but no serious infections or deaths. CONCLUSIONS: Anakinra was well tolerated, and may have some efficacy in reducing fever, markers of systemic inflammation, and coronary artery dilatation in IVIG-refractory KD.