{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T14:42:51Z","timestamp":1781016171487,"version":"3.54.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T00:00:00Z","timestamp":1689206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>This study aimed to gather evidence from clinical trials on the efficacy and safety of the available treatments for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) in children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This work adopted the Newcastle\u2013Ottawa scale to analyse the quality of the enrolled articles. A network meta-analysis was performed using clinical trials that compared drugs used to treat IVIG-resistant KD. Aggregate Data Drug Information System software v.1.16.5 was employed to analyse whether infliximab, second IVIG infusions, and intravenous pulse methylprednisolone (IVMP) were safe and effective.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten studies, involving 704 patients with IVIG-resistant KD, were identified and analysed. Overall, infliximab exhibited remarkable antipyretic activity compared with the second IVIG infusions (2.46, 1.00\u20136.94). According to the drug rank, infliximab was the best option against IVIG-resistant KD. Regarding adverse effects, the infliximab group was more prone to hepatomegaly. A second IVIG infusion was more likely to result in haemolytic anaemia. IVMP treatment was more susceptible to bradycardia, hyperglycaemia, hypertension, and hypothermia. In addition, infliximab, IVMP, and the second IVIG infusions showed no significant differences in the risk of developing a coronary artery aneurysm (CAA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Infliximab was the best option against IVIG-resistant KD, and IVMP, infliximab, and second IVIG infusions have not significant differences of prevent CAA in patients with IVIG-resistant KD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic Review Registration<\/jats:title><jats:p>Identifier: <jats:ext-link>https:\/\/osf.io\/3894y<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2023.1149519","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T15:12:33Z","timestamp":1689261153000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Treatment of immunoglobulin-resistant kawasaki disease: a Bayesian network meta-analysis of different regimens"],"prefix":"10.3389","volume":"11","author":[{"given":"Yan","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihong","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luoyi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1542\/pir.34.4.151","article-title":"Kawasaki disease","volume":"34","author":"Son","year":"2013","journal-title":"Pediatr Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"526969","DOI":"10.3389\/fped.2020.526969","article-title":"Cardiovascular involvement in kawasaki disease is much more than mere coronary arteritis","volume":"8","author":"Pilania","year":"2020","journal-title":"Front Pediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"216","DOI":"10.2188\/jea.JE20110126","article-title":"Epidemiologic features of kawasaki disease in Japan: results of the 2009\u20132010 nationwide survey","volume":"22","author":"Nakamura","year":"2012","journal-title":"J Epidemiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.jinf.2016.04.015","article-title":"Adjunctive therapies for kawasaki disease","volume":"72","author":"Campbell","year":"2016","journal-title":"J Inf Secur"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e927","DOI":"10.1161\/CIR.0000000000000484","article-title":"Diagnosis, treatment, and long-term management of kawasaki disease: a scientific statement for health professionals from the American heart association","volume":"135","author":"McCrindle","year":"2017","journal-title":"Circulation"},{"key":"B6","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s11926-020-00941-4","article-title":"Kawasaki disease: an update","volume":"22","author":"Rife","year":"2020","journal-title":"Curr Rheumatol Rep"},{"key":"B7","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s12016-016-8581-4","article-title":"Effect and safety of TNF inhibitors in immunoglobulin-resistant kawasaki disease: a meta-analysis","volume":"52","author":"Xue","year":"2016","journal-title":"Clin Rev Allergy Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s12887-019-1504-9","article-title":"Indirect-comparison meta-analysis of treatment options for patients with refractory kawasaki disease","volume":"19","author":"Chan","year":"2019","journal-title":"BMC Pediatr"},{"key":"B9","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s12016-016-8581-4","article-title":"Effect and safety of TNF inhibitors in immunoglobulin-resistant kawasaki disease: a meta-analysis. Meta-analysis","volume":"52","author":"Xue","year":"2017","journal-title":"Clin Rev Allergy Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"777","DOI":"10.7326\/M14-2385","article-title":"The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations","volume":"162","author":"Hutton","year":"2015","journal-title":"Ann Intern Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.jval.2011.04.002","article-title":"Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1","volume":"14","author":"Jansen","year":"2011","journal-title":"Value Health"},{"key":"B12","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1177\/0272989X12455847","article-title":"Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials","volume":"33","author":"Dias","year":"2013","journal-title":"Med Decis Mak"},{"key":"B13","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1016\/S2352-4642(21)00270-4","article-title":"Infliximab versus second intravenous immunoglobulin for treatment of resistant kawasaki disease in the USA (KIDCARE): a randomised, multicentre comparative effectiveness trial","volume":"5","author":"Burns","year":"2021","journal-title":"Lancet Child Adolesc Health"},{"key":"B14","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1136\/adc.2007.126144","article-title":"Effects of steroid pulse therapy on immunoglobulin-resistant kawasaki disease","volume":"93","author":"Furukawa","year":"2008","journal-title":"Arch Dis Child"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1038\/s41598-017-18387-7","article-title":"Infiximab versus intravenous immunoglobulin for refractory kawasaki disease: a phase 3, randomized, open-label, active-controlled, parallel-group, multicenter trial","volume":"8","author":"Mori","year":"2018","journal-title":"Sci Rep"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1007\/s00431-007-0642-5","article-title":"Effects of methylprednisolone pulse on cytokine levels in kawasaki disease patients unresponsive to intravenous immunoglobulin","volume":"167","author":"Miura","year":"2008","journal-title":"Eur J Pediatr"},{"key":"B17","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.jjcc.2008.08.002","article-title":"The strategy of immune globulin resistant kawasaki disease: a comparative study of additional immune globulin and steroid pulse therapy","volume":"53","author":"Ogata","year":"2009","journal-title":"J Cardiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.jpeds.2010.10.012","article-title":"Infliximab for intravenous immunoglobulin resistance in kawasaki disease: a retrospective study","volume":"158","author":"Son","year":"2011","journal-title":"J Pediatr"},{"key":"B19","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1007\/s00246-012-0589-9","article-title":"Steroid pulse therapy for children with intravenous immunoglobulin therapy-resistant kawasaki disease: a prospective study","volume":"34","author":"Teraguchi","year":"2013","journal-title":"Pediatr Cardiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1016\/S0140-6736(13)62298-9","article-title":"Infliximab for intensification of primary therapy for kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial","volume":"383","author":"Tremoulet","year":"2014","journal-title":"Lancet"},{"key":"B21","doi-asserted-by":"publisher","first-page":"4175821","DOI":"10.1155\/2020\/4175821","article-title":"Methylprednisolone pulse therapy or additional IVIG for patients with IVIG-resistant kawasaki disease","volume":"2020","author":"Wang","year":"2020","journal-title":"J Immunol Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1097\/INF.0000000000001039","article-title":"Infliximab as the first retreatment in patients with kawasaki disease resistant to initial intravenous immunoglobulin","volume":"35","author":"Youn","year":"2016","journal-title":"Pediatr Infect Dis J"},{"key":"B23","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/nrrheum.2015.54","article-title":"Kawasaki disease: insights into pathogenesis and approaches to treatment","volume":"11","author":"Shulman","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1016\/j.jacc.2015.12.073","article-title":"Kawasaki disease","volume":"67","author":"Newburger","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1542\/hpeds.2020-0188","article-title":"A cost comparison of infliximab versus intravenous immunoglobulin for refractory kawasaki disease treatment","volume":"11","author":"Scarlett","year":"2021","journal-title":"Hosp Pediatr"},{"key":"B26","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.pedneo.2018.03.005","article-title":"State-of-the-art acute phase management of Kawasaki disease after 2017 scientific statement from the American Heart Association","volume":"59","author":"Liu","year":"2018","journal-title":"Pediatr Neonatol"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2023.1149519\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T15:12:35Z","timestamp":1689261155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2023.1149519\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,13]]},"references-count":26,"alternative-id":["10.3389\/fped.2023.1149519"],"URL":"https:\/\/doi.org\/10.3389\/fped.2023.1149519","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,13]]},"article-number":"1149519"}}