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

Arthritis Rheumatol. 2023 Aug;75(8):1466-1476. doi: 10.1002/art.42495. Epub 2023 May 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • C-Reactive Protein
  • Child
  • Connective Tissue Diseases*
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Interleukin 1 Receptor Antagonist Protein* / therapeutic use
  • Retrospective Studies
  • Stroke Volume
  • Ventricular Function, Left


  • Interleukin 1 Receptor Antagonist Protein
  • Immunoglobulins, Intravenous
  • C-Reactive Protein
  • Glucocorticoids

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related