Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children

• Published in: JAMA : the journal of the American Medical Association Vol. 325; no. 9; pp. 855 - 864
• Main Authors: Ouldali, Naïm, Toubiana, Julie, Antona, Denise, Javouhey, Etienne, Madhi, Fouad, Lorrot, Mathie, Léger, Pierre-Louis, Galeotti, Caroline, Claude, Caroline, Wiedemann, Arnaud, Lachaume, Noémie, Ovaert, Caroline, Dumortier, Morgane, Kahn, Jean-Emmanuel, Mandelcwajg, Alexis, Percheron, Lucas, Biot, Blandine, Bordet, Jeanne, Girardin, Marie-Laure, Yang, David Dawei, Grimaud, Marion, Oualha, Mehdi, Allali, Slimane, Bajolle, Fanny, Beyler, Constance, Meinzer, Ulrich, Levy, Michael, Paulet, Ana-Maria, Levy, Corinne, Cohen, Robert, Belot, Alexandre, Angoulvant, François
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 02.03.2021; American Medical Association (AMA)
• Subjects: Adolescent; Child; Child, Preschool; Children; Combined Modality Therapy; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - drug therapy; COVID-19 - therapy; COVID-19 Drug Treatment; Female; Fever; Fever - etiology; France; Glucocorticoids; Glucocorticoids - adverse effects; Glucocorticoids - therapeutic use; Health services; Heart; Hemodynamics; Humans; Immunoglobulins; Immunoglobulins, Intravenous; Immunoglobulins, Intravenous - therapeutic use; Inflammation; Intensive care; Intensive Care Units, Pediatric; Intravenous administration; Length of Stay; Life Sciences; Male; Methylprednisolone; Methylprednisolone - adverse effects; Methylprednisolone - therapeutic use; Multisystem inflammatory syndrome in children; Online First; Original Investigation; Pediatrics; Propensity Score; Public health; Recurrence; Respiratory diseases; Retrospective Studies; Risk; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Systemic Inflammatory Response Syndrome; Systemic Inflammatory Response Syndrome - complications; Systemic Inflammatory Response Syndrome - drug therapy; Systemic Inflammatory Response Syndrome - therapy; Therapy; Treatment Outcome; Ventricle; Viral diseases; France
• ISSN: 0098-7484; 1538-3598; 1538-3598
• DOI: 10.1001/jama.2021.0694

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.