Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA.
J Pediatr. 2022 Apr;243:173-180.e8. doi: 10.1016/j.jpeds.2021.12.035. Epub 2021 Dec 23.
To determine the safety, pharmacokinetics, and immunomodulatory effects of 2-6 weeks of anakinra therapy in patients with acute Kawasaki disease with a coronary artery aneurysm (CAA).
We performed a Phase I/IIa dose-escalation study of anakinra (2-11 mg/kg/day) in 22 patients with acute Kawasaki disease with CAA. We measured interleukin (IL)-1RA concentrations after the first dose and trough levels up to study week 6. Markers of inflammation and coronary artery z-scores were assessed pretreatment and at 48 hours, 2 weeks, and 6 weeks after initiation of therapy.
Up to 6 weeks of anakinra (up to 11 mg/kg/day) was safe and well tolerated by the 22 participants (median age, 1.1 years), with no serious adverse events attributable to the study drug. All participants were treated with intravenous immunoglobulin (IVIG), and 20 also received infliximab (10 mg/kg) before initiation of anakinra. Serum levels of IL-6, IL-8, and tumor necrosis factor α decreased similarly in patients with Kawasaki disease treated with IVIG, infliximab, and anakinra compared with age- and sex-matched patients with Kawasaki disease treated only with IVIG and infliximab. Anakinra clearance increased with illness day at diagnosis. Simulations demonstrated that more frequent intravenous (IV) dosing may result in more sustained concentrations without significantly increasing the peak concentration compared with subcutaneous (SC) dosing.
Both IV and SC anakinra are safe in infants and children with acute Kawasaki disease and CAA. IV dosing every 8-12 hours during the acute hospitalization of patients with Kawasaki disease may result in a sustained concentration while avoiding frequent SC injections. The efficacy of a short course of IV therapy during hospitalization should be studied. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT02179853.
确定在伴有冠状动脉瘤（CAA）的急性川崎病患者中，接受 2-6 周的阿那白滞素治疗的安全性、药代动力学和免疫调节作用。
我们对 22 例伴有 CAA 的急性川崎病患者进行了阿那白滞素（2-11mg/kg/天）的 I/IIa 剂量递增研究。我们在首次给药后测量白细胞介素（IL）-1RA 浓度，并在研究周 6 时测量浓度最低点。在治疗开始前、48 小时、2 周和 6 周时评估炎症标志物和冠状动脉 z 评分。
在 22 名参与者（中位年龄 1.1 岁）中，高达 6 周的阿那白滞素（高达 11mg/kg/天）是安全且耐受良好的，没有因研究药物而发生严重不良事件。所有参与者均接受静脉注射免疫球蛋白（IVIG）治疗，20 名参与者在开始阿那白滞素治疗前还接受了英夫利昔单抗（10mg/kg）治疗。与仅接受 IVIG 和英夫利昔单抗治疗的川崎病年龄和性别匹配的患者相比，接受 IVIG、英夫利昔单抗和阿那白滞素治疗的川崎病患者的血清 IL-6、IL-8 和肿瘤坏死因子-α 水平下降相似。阿那白滞素清除率随发病日而增加。模拟结果表明，与皮下（SC）给药相比，更频繁的静脉（IV）给药可能会导致更持续的浓度，而不会显著增加峰值浓度。
在伴有 CAA 的急性川崎病婴儿和儿童中，IV 和 SC 阿那白滞素均安全。在川崎病患者的急性住院期间，每 8-12 小时进行 IV 给药可能会在避免频繁 SC 注射的同时保持持续浓度。应研究住院期间短疗程 IV 治疗的疗效。
CLINICALTRIALS.GOV：NCT02179853。
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