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

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 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.