Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children
Naïm Ouldali, Julie Toubiana, Denise Antona, Étienne 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, Michaël Levy, Ana-Maria Paulet, Corinne Levy, Robert Cohen, Alexandre Bélot, François Angoulvant, Cinthia Rames, A. Donzeau, Sophie Léty, Cristian Fedorczuk, Marion Lajus, Philippe Bensaïd, Yacine Laoudi, Charlotte Pons, Camille Beaucourt, Loïc de Pontual, Camille Aupiais, Alain Lefèvre‐Utile, Muriel Richard, Etienne Goisque, Xavier Iriart, Olivier Brissaud, Marion Bailhache, Pierre Segretin, Julie Molimard, Marie-Clothilde Orcel, Grégoire Benoist, Elsa Amouyal, Margaux Guerder, Robin Pouyau, Jean-Marie De Guillebon De Resnes, Ellia Mezgueldi, Fleur Cour‐Andlauer, Côme Horvat, Pierre Poinsot, Cécile Frachette, Antoine Ouziel, Yves Gillet, Catherine Barrey, Jacques Brouard, Caroline Faucon, Henri Giniès, Vathanaksambath Ro, Narcisse Elanga, Vincent Gajdos, Romain Basmaci, Névéna Danékova, 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 S. Semama, Frédéric Huet, Mayssa Sarakbi, Guillaume Mortamet, C. Bost-Bru, Charlotte Kevorkian‐Verguet, Matthias Lachaud, Caroline Vinit, Véronique Hentgen, Pascal Leroux, Valérie Bertrand, Caroline Parrod, Irina Craiu
Abstract
Importance: 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. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: 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. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: 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. Results: 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]; P = .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]; P = .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]). Conclusions and Relevance: 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.