Multisystem Inflammatory Syndrome Therapies in Children: A Comparative Effectiveness Trial

Background: Despite significant morbidity and mortality due to Multisystem Inflammatory Syndrome in Children (MIS-C) following SARS-CoV2 infection, there is clinical equipoise as to the best treatment regimen for MIS-C. This study aimed to determine the anti-inflammatory medication (infliximab, steroids, or anakinra) in combination with IVIG that is most effective in treating MIS-C. Methods: Multisystem Inflammatory Syndrome Therapies in Children (MISTIC) is a comparative effectiveness study conducted at two hospitals in the United States. Children <21 years with MIS-C who required additional anti-inflammatory therapy beyond IVIG (2g/kg) were eligible. Participants were randomized to infliximab (10 mg/kg IV once over 2 hours), methylprednisolone (2 mg/kg/day IV or orally divided q12h; max 60 mg/day), or anakinra (up to 10 mg/kg/day IV). The primary outcome was the difference in the need for second randomization among the treatment arms. Clinical and laboratory data, including echocardiograms and adverse events, were assessed prior to any treatment, after completion of each arm of randomization, and up to 6 weeks after discharge from the hospital. Findings: Between December 21, 2020 and October 31, 2022, 71 participants completed the study. After adjusting for age and sex, the odds of needing second randomization were 3·4 times higher when the first randomized drug was anakinra as compared to infliximab (OR=3·42, 95% CI: 1·03 – 12·29, p = 0·049) while similar when the first randomized drug was steroids or infliximab. Twenty-eight adverse events were recorded over the course of the study, none of which were serious. Of these, 17 (60·7%) were adjudicated to be possibly, probably or definitely related to a study treatment with 16 (94·1%) attributed to steroids and 1 (5·9%) attributed to anakinra. Interpretation: The odds of needing second randomization were higher when the first randomized drug received was anakinra as compared to infliximab or steroids.