Phase II Open Label Study of 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 & rheumatology (Hoboken, N.J.); 73,1:151-161. February 2021

Affiliations: CeRéMAIA, AP‐HP, Bicêtre Hospital, University of Paris Sud Saclay, Paris, France University of Toulouse, Toulouse, France. University of Lyon, International Center for Research in Infectious Diseases, INSERM U1111, ENS, Lyon, France.

Abstract: OBJECTIVE: Anakinra has been shown to be successful in preventing and treating cardiovascular lesions both in experimental murine models of Kawasaki disease (KD) and in several studies on intravenous immunoglobulin (IVIG)- and steroid-resistant patients with KD. This study was undertaken to determine the safety of blocking interleukin-1 in patients with IVIG-resistant KD. METHODS: Sixteen patients were included in the present study. Patients with KD who were not responsive to 1 or more courses of 2 mg/kg of IVIG received anakinra by subcutaneous daily injections. Starting doses were 2 mg/kg of IVIG (4 mg/kg in patients who were age <8 months and who weighed 5 kilograms), and the dose was increased up to 6 mg/kg every 24 hours if the patient’s body temperature remained >38°C, indicative of a fever. Treatment duration was 14 days. The last visit was on day 45. Primary outcome was abatement of fever. Secondary measures included disease activity, coronary artery Z score, and C-reactive protein (CRP) levels. RESULTS: Seventy-five percent 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 indicated on 93.3% (95% confidence interval [95% CI] 68.1-99.8%) of physician evaluations and on 100% (95% CI 73.5-100%) of parent evaluations. CRP values normalized by day 30. At the initial screening, 12 of 16 patients had a maximum coronary artery Z score of >2, and 10 of 16 patients had a maximum Z score of >2.5. At day 45, 5 of 10 patients (50% [95% CI 18.7-81.3%]) and 6 of 12 patients (50% [95% CI 21.1-78.9%]) had achieved coronary artery Z scores of <2.5 and <2, respectively. Five serious adverse events were observed in 3 patients, but no serious infections or deaths occurred. CONCLUSION: Anakinra was well tolerated in the study patients and may have some efficacy in reducing fever, markers of systemic inflammation, and coronary artery dilatation in individuals with IVIG-refractory KD.