Treatment of Multisystem Inflammatory Syndrome in Children

PURPOSE OF STUDY: To summarize the evidence on treatments for multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children. STUDY POPULATION: Pediatric patients with suspected MIS-C or other inflammatory illness after SARS-CoV-2 infection between June 20th, 2020 and February 24th, 2021. METHODS: Pediatricians worldwide were invited to upload their data into a central database for any pediatric patient with suspected MIS-C or any inflammatory disease after SARS-CoV-2 infection. Deidentified data, including demographics, clinical features, laboratory results, treatments (including intravenous immunoglobulin [IVIG], glucocorticoid, and biologic medications), and hospital stay length were collected and analyzed. Three primary treatment groups were compared: IVIG alone, IVIG plus glucocorticoid, and glucocorticoid alone, with IVIG alone classified as primary treatment based upon prestudy acceptance of IVIG as a primary treatment. Day 0 was considered the first calendar day of treatment of each treatment modality. There were 2 primary outcomes: (1) inotropic or mechanical ventilation (invasive or noninvasive) by day 2 or later or death;(2) reduction in disease severity on a seven-point scale between day 0 and 2. A subgroup analysis of only those meeting World Health Organization (WHO) criteria for MIS-C were included. Secondary outcomes included trends in inflammatory markers, escalation of immunomodulators, time to decrease in disease severity by 1 point, left ventricular dysfunction on echocardiogram, coronary artery aneurysm after treatment and increase in cardiorespiratory support after day 0. RESULTS: A total of 614 patients, among 81 hospitals in 34 countries, had suspected MIS-C. Of these, 246 received primary treatment with IVIG, 208 with IVIG plus glucocorticoid, and 99 with glucocorticoid alone. An additional 22 patients received immunomodulators, and 39 patients received no immunomodulatory treatment. Troponin levels and percentage of patients on inotropic agents on day 0 were higher in the IVIG plus glucocorticoid group. The first primary outcome occurred in 56 patients with IVIG plus glucocorticoid (odds ratio [OR] 0.77 compared with IVIG alone;95% confidence interval [CI], 0.33 to 1.82) and in 17 patients on glucocorticoids alone (OR 0.54;95% CI, 0.22 to 1.33). In the subgroup analysis, 490 (80%) patients met WHO criteria for MIS-C and the first primary outcome occurred in 40 patients on IVIG and glucocorticoids (OR 0.95) and in 12 patients on glucocorticoids alone (OR 0.3). The second primary outcome occurred in 54 patients on IVIG plus glucocorticoids (OR 0.9) and in 20 patients on glucocorticoids alone (OR 0.93) among the entire group. In the subgroup that met MIS-C criteria, a second primary outcome event occurred in 52 patients on IVIG plus glucocorticoids (OR 1.09) and in 16 patients on glucocorticoids alone (OR 1.95). Regarding secondary outcomes, escalation of immunomodulatory treatment was less common in IVIG plus glucocorticoids (OR 0.18), though inconclusive in the glucocorticoid versus IVIG group (OR 1.31). There was no clear difference in inflammatory markers, inotropic support, or mechanical ventilation in groups who had escalation of care by day 2 versus those without escalation in care. CONCLUSIONS: There were no significant differences in the primary outcomes for patients receiving IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone. When restricted to only those who met WHO MIS-C criteria, there was modest evidence of benefit in use of glucocorticoids compared with IVIG alone. There were no major differences in secondary outcomes, with the exception of lower odds of immunomodulatory treatment escalation in patients in IVIG plus glucocorticoids.