Treatment of Multisystem Inflammatory Syndrome in Children: Understanding Differences in Results of Comparative Effectiveness Studies

OBJECTIVE: Two cohort studies in patients with multisystem inflammatory syndrome in children (MIS‐C) demonstrated contrasting results regarding the benefit of initial immunomodulatory treatment with intravenous immunoglobulin (IVIG) alone versus IVIG and glucocorticoids. We sought to determine whether application of different MIS‐C definitions and differing disease severity between cohorts underlay discrepant results. METHODS: The Overcoming COVID‐19 Public Health Surveillance Registry (OC‐19) included patients meeting the US Centers for Disease Control and Prevention (CDC) MIS‐C definition, whereas the Best Available Treatment Study (BATS) applied the World Health Organization (WHO) definition. We applied the WHO definition to the OC‐19 cohort and the CDC definition to the BATS cohort and determined the proportion that did not meet the alternate definition. We compared illness severity indicators between cohorts. RESULTS: Of 349 OC‐19 patients, 9.5% did not meet the WHO definition. Of 350 BATS patients, 10.3% did not meet the CDC definition. Most organ system involvement was similar between the cohorts, but more OC‐19 patients had WHO‐defined cardiac involvement (87.1% vs 79.4%, P = 0.008). OC‐19 patients were more often admitted to intensive care (61.0% vs 44.8%, P < 0.001) and more often received vasopressors or inotropes (39.5% vs 22.9%, P < 0.001) before immunomodulatory treatment. CONCLUSION: Greater illness severity and cardiovascular involvement in the OC‐19 cohort compared with the BATS cohort, and not use of different MIS‐C case definitions, may have contributed to differing study conclusions about optimal initial treatment for MIS‐C. Disease severity should be considered in future MIS‐C study designs and treatment recommendations to identify patients who would benefit from aggressive immunomodulatory treatment.