Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes

PURPOSE OF THE STUDY: Given the similarities between multisystem inflammatory syndrome in children (MIS-C) and Kawasaki's disease, most patients with MIS-C have been treated with intravenous immune globulin (IVIG), the standard of care for Kawasaki's disease. However, other immunomodulatory therapies, including corticosteroids and biologics, have been used to counter the cytokine-related inflammatory changes in MIS-C. The purpose of this study was to describe the pattern of immunomodulatory therapies used in patients with MIS-C in the United States and to assess the relative effectiveness of IVIG plus corticosteroids (CSTs), compared with IVIG alone, in the initial treatment of MIS-C. STUDY POPULATION: The Overcoming COVID-19 surveillance registry identified 596 patients as having MIS-C at each of the 58 participating hospitals between March 15 and October 31, 2020. Of these, 518 (87%) were flagged as receiving at least 1 immunomodulatory treatment. The researchers then analyzed longitudinal data collected in this cohort, including demographic characteristics, underlying medical conditions, signs and symptoms at presentation, clinical course, laboratory test results, diagnostic studies, treatments, complications, and outcomes. METHODS: Statistical comparisons between IVIG+CSTs and IVIG treatment groups were done by population sampling using propensity score matching;among the patients treated with IVIG plus glucocorticoids or IVIG alone on day 0, a total of 206 could be matched at a 1:1 ratio and based on propensity scores. To compare the potential effectiveness of initial immunomodulatory treatment, the authors prespecified a primary composite outcome of cardiovascular dysfunction (left ventricular ejection fraction < 55% and/or shock needing vasopressor support) on day 2 or beyond, up until discharge. Secondary outcome measures included the primary outcome components, escalation of immunomodulation treatment after day 1, and recurrent or persistent fever on day 2 and beyond. The potential effectiveness of treatment in primary and secondary outcomes was also assessed using an inverse-probability weighted analysis. RESULTS: Of the patients treated, 241 (47%) received IVIG and CSTs;107 (21%) received IVIG, CSTs, and a biologic (anakinra, etanercept, infliximab, or tocilizumab);89 (17%) received IVIG only;and 81 (16%) received other treatments, including CSTs only, a biologic only, CSTs and a biologic, or IVIG and a biologic. Highest illness severity was seen in the 107 patients who received IVIG, CSTs, and a biologic combined. Treatment patterns changed over time, with an observed decrease in the fraction of cases treated with IVIG alone, offset primarily by an increase in the use of IVIG with CSTs together. In the propensity-score-matched analysis, initial treatment with IVIG + CSTs was associated with a lower risk of cardiovascular dysfunction and less escalation of immunomodulatory treatments later in hospitalization, but the risks of persistent or recurrent fever and length of stay in the ICU were not clearly lower. The inverse-probability-weighted analysis confirmed the findings of the propensity-score-matched analysis. CONCLUSIONS: The authors found that initial treatment with IVIG plus glucocorticoids for MIS-C was associated with a lower risk of cardiovascular dysfunction than initial treatment with IVIG alone.