학술논문
Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study
Document Type
article
Author
Channon-Wells, Samuel; Vito, Ortensia; McArdle, Andrew J; Seaby, Eleanor G; Patel, Harsita; Shah, Priyen; Pazukhina, Ekaterina; Wilson, Clare; Broderick, Claire; D'Souza, Giselle; Keren, Ilana; Nijman, Ruud G; Tremoulet, Adriana; Munblit, Daniel; Ulloa-Gutierrez, Rolando; Carter, Michael J; Ramnarayan, Padmanabhan; De, Tisham; Hoggart, Clive; Whittaker, Elizabeth; Herberg, Jethro A; Kaforou, Myrsini; Cunnington, Aubrey J; Blyuss, Oleg; Levin, Michael; consortium, Best Available Treatment Study; Chouli, Mohamed; Hamadouche, Nacera; Ladj, Mohamed Samir; Vázquez, Jorge Agrimbau; Carmona, Rodrigo; Collia, Adrian Gustavo; Ellis, Alejandro; Natta, Diego; Pérez, Laura; Rubiños, Mayra; Veliz, Natalia; Yori, Silvana; Britton, Philip N; Burgner, David P; Carey, Emma; Crawford, Nigel W; Giuliano, Hayley; McMinn, Alissa; Wong, Shirley; Wood, Nicholas; Holter, Wolfgang; Krainz, Matthias; Ulreich, Raphael; Zurl, Christoph; Dehoorne, Joke; Haerynck, Filomeen; Hoste, Levi; Schelstraete, Petra; Vandekerckhove, Kristof; Willems, Jef; Farias, Camila Giuliana Almeida; Almeida, Flávia Jacqueline; Leal, Izabel Alves; da Silva, André Ricardo Araujo; Araujo e Silva, Anna Esther; Barreiro, Sabrina TA; da Silva, Daniella Gregória Bomfim Prado; Cervi, Maria Celia; dos Santos Naja Cardoso, Mirian Viviane; Teixeira, Cristiane Henriques; Jarovsky, Daniel; Araujo, Julienne Martins; Berezin, Eitan Naaman; Sáfadi, Marco Aurélio Palazzi; la Ossa, Rolando Andres Paternina-de; Vieira, Cristina Souza; Dimitrova, Anna; Ganeva, Margarita; Stefanov, Stefan; Telcharova-Mihaylovska, Albena; Biggs, Catherine M; Lopez, Alison; Scuccimarri, Rosie; Tan, Ryan; Wasserman, Sam; Withington, Davinia; Ampuero, Camila; Aravena, Javiera; B, Raul Bustos; Casanova, Daniel; Cruces, Pablo; Diaz, Franco; García-Salum, Tamara; Godoy, Loreto; Medina, Rafael A; Galaz, Gonzalo Valenzuela; Camacho-Moreno, Germán; Avila-Aguero, María L; Brenes-Chacón, Helena; Camacho-Badilla, Kattia; Ivankovich-Escoto, Gabriela; Naranjo-Zuniga, Gabriela; Soriano-Fallas, Alejandra
Source
The Lancet Rheumatology. 5(4)
Subject
Language
Abstract
BackgroundMultisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments.MethodsThe Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370.FindingsWe enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p