Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children
Authors: Naïm Ouldali, Julie Toubiana, Denise Antona, Etienne Javouhey, Fouad Madhi, Mathie Lorrot, Pierre-Louis Léger, Caroline Galeotti, Caroline Claude, Arnaud Wiedemann, Noémie Lachaume, Caroline Ovaert, Morgane Dumortier, Jean-Emmanuel Kahn, Alexis Mandelcwajg, Lucas Percheron, Blandine Biot, Jeanne Bordet, Marie-Laure Girardin, David Dawei Yang, Marion Grimaud, Mehdi Oualha, Slimane Allali, Fanny Bajolle, Constance Beyler, Ulrich Meinzer, Michael Levy, Ana-Maria Paulet, Corinne Levy, Robert Cohen, Alexandre Belot, François Angoulvant, Cinthia Rames, Aurelie Donzeau, Sophie Lety, Cristian Fedorczuk, Marion Lajus, Philippe Bensaid, Yacine Laoudi, Charlotte Pons, Camille Beaucourt, Loïc De Pontual, Camille Aupiais, Alain Lefevre-Utile, Muriel Richard, Etienne Goisque, Xavier Iriart, Olivier Brissaud, Marion Bailhache, Pierre Segretin, Julie Molimard, Marie-Clothilde Orcel, Gregoire Benoist, Elsa Amouyal, Margaux Guerder, Robin Pouyau, Jean-Marie De Guillebon De Resnes, Ellia Mezgueldi, Fleur Cour-Andlauer, Come Horvat, Pierre Poinsot, Cecile Frachette, Antoine Ouziel, Yves Gillet, Catherine Barrey, Jacques Brouard, Caroline Faucon, Henri Ginies, Vathanaksambath Ro, Narcisse Elanga, Vincent Gajdos, Romain Basmaci, Nevena Danekova, Hadile Mutar, Sébastien Rouget, Xavier Torterüe, Elodie Nattes, Isabelle Hau, Sandra Biscardi, Houmam El Jurdi, Camille Jung, Ralph Epaud, Céline Delestrain, Adèle Carlier-Gonod, Camille Chavy, Benoît Colomb, Stéphanie Litzler-Renault, Denis Semama, Frederic Huet, Mayssa Sarakbi, Guillaume Mortamet, Cécile Bost-Bru, Charlotte Kevorkian-Verguet, Matthias Lachaud, Caroline Vinit, Véronique Hentgen, Pascal Leroux, Valérie Bertrand, Caroline Parrod, Irina Craiu, Isabelle Kone-Paut, Philippe Durand, Pierre Tissiere, Luc Morin, Jordi Miatello, Guillaume Morelle, Tamazoust Guiddir, Charlotte Borocco, Camille Guillot, Stéphane Leteurtre, François Dubos, Mylene Jouancastay, Morgan Recher, Alain Martinot, Valentine Voeusler, Jeanne Languepin, Aurélie Morand, Emmanuelle Bosdure, Violaine Bresson, Noémie Vanel, Fabrice Ughetto, Fabrice Michel, Caujolle Marie, Renaud Blonde, Jacqueline Nguyen, Nathalie Garrec, Arnaud Chalvon-Demersay, Caroline Masserot-Lureau, Anne-Sophie Colas, Claire Ferrua, Anis Larakeb, Sakina Benkaddouss, Laurence Mathivon, Marie Monfort, Sanaa Naji, Aurelia Carbasse, Christophe Milesi, Cyril Schweitzer, Nathan Giroux, Noël Boussard, Benedicte Romefort, Elise Launay, Christèle Gras-Le Guen, Ahmed Ali, Nathalie Blot, Antoine Tran, Anne Rancurel, Hervé Haas, Mickael Afanetti, Julie Bernardor, Deborah Talmud, Imen Jhaouat, Françoise Monceaux, Anaïs Chosidow, Anne-Sophie Romain, Emmanuel Grimprel, Jérôme Rambaud, Sandrine Jean, Julie Starck, Yaël Levy, Romain Guedj, Ricardo Carbajal, Pauline Parisot, Géraldine Poncelet, Richard Wolff, Boris Lacarra, Arielle Maroni, Jérôme Naudin, Guillaume Geslin, Laure Maurice, Anna Deho, Fleur Lebourgeois, Marilyne Chomton, Stephane Dauger, Mathieu Genuini, Chérine Benzouid, Johanna Lokmer, Ronan Bonnefoy, Isabelle Melki, Glory Dingulu, Jean Gaschignard, Camille Ducrocq, Marie Pouletty, Olivier Corseri, Albert Faye, Alexis Rybak, Luigi Titomanlio, Marie-Françoise Hurtaux, Guislaine Garcelain, Stéphane Bonacorsi, Philippe Bidet, André Birgy, Sylvain Renolleau, Fabrice Lesage, Florence Moulin, Laurent Dupic, Laure de Saint Blanquat, Claire Heilbronner, Meryl Vedrenne-Cloquet, Elodie Salvador, Matthieu Bendavid, Charles De Marcellus, Judith Chareyre, Yael Pinhas, Joséphine Brisse, Melissa Taylor, Agathe Debray,, Pauline Adnot, Martin Chalumeau, Véronique Abadie, Pierre Frange, Jeremie F Cohen, William Curtis, Hélène Chappuy, Zahra Belhadjer, Johanne Auriau, Mathilde Méot, Lucile Houyel, Damien Bonnet, Christophe Delacourt, David Drummond, Brigitte Bader-Meunier, Pierre Quartier, Frédérique Delion, Philippe Blanc, Elisabeth Caron, Natacha Maledon, Blandine Robert, Letitia Pantalone, Hanane Kouider, Camille Loeile, Gauthier Loron, Cécile Vittot, Thierry Blanc, Didier Pinquier, François Buisson, Hugues Flodrops, Jamal-Bey Karim, Raphaëlle Sarton, Fadhila Mokraoui, Simon Escoda, Nina Deschamps, Laurent Bonnemains, Sarah-Louisa Mahi, Clara Mertes, Joelle Terzic, Charlotte Idier, Ariane Benezech, Thomas Simon, Stephane Decramer, Clement Karsenty, Camille Brehin, Soraya Chenichene, Nicoleta-Magdolena Ursulescu, Céline Manteau, Marie Delattre, Bérengère Dalichoux
Journal: JAMA (2021)

<h3>Importance</h3> Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. <h3>Objective</h3> To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. <h3>Design, Setting, and Participants</h3> Retrospective cohort study drawn from a national surveillance system with propensity score–matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. <h3>Exposures</h3> IVIG and methylprednisolone vs IVIG alone. <h3>Main Outcomes and Measures</h3> The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. <h3>Results</h3> Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, −0.28 [95% CI, −0.48 to −0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70];<i>P</i> = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, −0.22 [95% CI, −0.40 to −0.04]; OR, 0.19 [95% CI, 0.06 to 0.61];<i>P</i> = .004), hemodynamic support (absolute risk difference, −0.17 [95% CI, −0.34 to −0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, −0.18 [95% CI, −0.35 to −0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, −2.4 [95% CI, −4.0 to −0.7]). <h3>Conclusions and Relevance</h3> Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.