PMID- 34953816 OWN - NLM STAT- MEDLINE DCOM- 20220428 LR - 20220531 IS - 1097-6833 (Electronic) IS - 0022-3476 (Linking) VI - 243 DP - 2022 Apr TI - Anakinra Treatment in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysms: A Phase I/IIa Trial. PG - 173-180.e8 LID - S0022-3476(21)01242-7 [pii] LID - 10.1016/j.jpeds.2021.12.035 [doi] AB - OBJECTIVES: 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). STUDY DESIGN: 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. RESULTS: 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 alpha 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. CONCLUSIONS: 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. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Yang, Jincheng AU - Yang J AD - 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. FAU - Jain, Sonia AU - Jain S AD - Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA. FAU - Capparelli, Edmund V AU - Capparelli EV AD - 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. FAU - Best, Brookie M AU - Best BM AD - 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. FAU - Son, Mary Beth AU - Son MB AD - Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Boston, MA. FAU - Baker, Annette AU - Baker A AD - Department of Cardiology, Boston Children's Hospital, Boston, MA. FAU - Newburger, Jane W AU - Newburger JW AD - Department of Cardiology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA. FAU - Franco, Alessandra AU - Franco A AD - Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA. FAU - Printz, Beth F AU - Printz BF AD - Division of Pediatric Cardiology, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA. FAU - He, Feng AU - He F AD - Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA. FAU - Shimizu, Chisato AU - Shimizu C AD - Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA. FAU - Hoshino, Shinsuke AU - Hoshino S AD - Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA. FAU - Bainto, Emelia AU - Bainto E AD - Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA. FAU - Moreno, Elizabeth AU - Moreno E AD - Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA. FAU - Pancheri, Joan AU - Pancheri J AD - Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA. FAU - Burns, Jane C AU - Burns JC AD - Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA. FAU - Tremoulet, Adriana H AU - Tremoulet AH AD - Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA. Electronic address: atremoulet@health.ucsd.edu. LA - eng SI - ClinicalTrials.gov/NCT02179853 GR - T32 HD087978/HD/NICHD NIH HHS/United States GR - R01 HL140898/HL/NHLBI NIH HHS/United States PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20211223 PL - United States TA - J Pediatr JT - The Journal of pediatrics JID - 0375410 RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Interleukin 1 Receptor Antagonist Protein) RN - B72HH48FLU (Infliximab) SB - IM MH - Acute Disease MH - *Coronary Aneurysm/complications/drug therapy MH - Female MH - Humans MH - Immunoglobulins, Intravenous/therapeutic use MH - Infant MH - Infliximab/therapeutic use MH - *Interleukin 1 Receptor Antagonist Protein/adverse effects MH - Male MH - *Mucocutaneous Lymph Node Syndrome/complications/drug therapy OTO - NOTNLM OT - Kawasaki disease OT - anakinra OT - coronary artery abnormalities OT - interleukin-1 EDAT- 2021/12/27 06:00 MHDA- 2022/04/29 06:00 CRDT- 2021/12/26 20:32 PHST- 2021/08/31 00:00 [received] PHST- 2021/12/08 00:00 [revised] PHST- 2021/12/17 00:00 [accepted] PHST- 2021/12/27 06:00 [pubmed] PHST- 2022/04/29 06:00 [medline] PHST- 2021/12/26 20:32 [entrez] AID - S0022-3476(21)01242-7 [pii] AID - 10.1016/j.jpeds.2021.12.035 [doi] PST - ppublish SO - J Pediatr. 2022 Apr;243:173-180.e8. doi: 10.1016/j.jpeds.2021.12.035. Epub 2021 Dec 23.