Variation in Early Anakinra Use and Short-Term Outcomes in Multisystem Inflammatory Syndrome in Children

Abstract

Objective: Evidence regarding effectiveness of interleukin-1 receptor antagonism in Multisystem Inflammatory Syndrome in Children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy. Methods: We conducted a retrospective cohort study of MIS-C cases in a U.S. surveillance registry November 2020-December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0–1) were identified. We compared cases ages 2–20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids vs. anakinra plus IVIG and/or glucocorticoids (days 0–1), using inverse probability weighting to balance severity. Primary outcomes were vasopressor requirement (day 3) and impaired left ventricular ejection fraction (days 3–4). The secondary outcome was 50% reduction in C-reactive protein (day 3). Results: Among 1516 MIS-C cases (44 sites), 193 (13%) received anakinra alone or with other immunomodulators as initial treatment (range 0–74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (N=121) vs. IVIG and glucocorticoids (N=389) was not associated with significant differences in vasopressor requirement (25.6% vs. 20.1%; RR 1.27, 95% CI [0.88–1.84]), ventricular dysfunction (33.7% vs. 25.7%; RR 1.31, 95% CI [0.98–1.75]), or C-reactive protein reduction. Conclusions: We identified substantial variation in initial anakinra use in a real-world population of children with MIS-C, but no average short-term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone.