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

  • the Overcoming COVID-19 Investigators
  • Harvard University
  • Boston Children's Hospital
  • Baylor College of Medicine
  • University of Utah
  • University of Colorado Anschutz Medical Campus
  • Indiana University Bloomington
  • Vanderbilt University
  • Rady Children's Hospital
  • University of Mississippi
  • Nationwide Children’s Hospital
  • University of Alabama at Birmingham
  • Children's Hospital of The King's Daughters Health System
  • Children’s Mercy Kansas City
  • University of Pennsylvania
  • New York Medical College
  • University of Iowa
  • Akron Children's Hospital
  • Oakland Children's Hospital
  • Medical University of South Carolina
  • University of California at Irvine
  • Children's Hospital of Michigan
  • Centers for Disease Control and Prevention

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 US surveillance registry from November 2020 to 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 in patients ages 2–20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days 0–1, using inverse probability weighting to balance disease severity. Primary outcomes were vasopressor requirement on day 3 and impaired left ventricular ejection fraction on days 3–4. The secondary outcome was 50% reduction in C-reactive protein on day 3. Results: Among 1,516 MIS-C cases at 44 sites, 193 (13%) patients 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 disease severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (n = 121) versus IVIG plus glucocorticoids (n = 389) was not associated with significant differences in vasopressor requirement (25.6% versus 20.1%, respectively; risk ratio [RR] 1.27 [95% confidence interval (95% CI) 0.88–1.84]), ventricular dysfunction (33.7% versus 25.7%, respectively; RR 1.31 [95% CI 0.98–1.75]), or C-reactive protein reduction. Conclusion: 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.

Original languageEnglish
Pages (from-to)1466-1476
Number of pages11
JournalArthritis and Rheumatology
Volume75
Issue number8
DOIs
StatePublished - Aug 2023

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