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Variation in Early Anakinra Use and Short-Term Outcomes in Multisystem Inflammatory Syndrome in Children
Joyce C Chang1, Cameron C Young2, Eyal Muscal3
1Division of Immunology, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
Insights
Early anakinra treatment did not improve cardiovascular outcomes in children with multisystem inflammatory syndrome (MIS-C). This study found significant variation in anakinra use but no average short-term benefit over standard therapy.
Area of Science:
- Pediatric rheumatology
- Pediatric critical care
- Immunology
Background:
- Multisystem inflammatory syndrome in children (MIS-C) is a serious condition requiring prompt treatment.
- Interleukin-1 receptor antagonism, specifically with anakinra, is a potential therapeutic option, but its effectiveness in MIS-C is not well-established.
- Understanding treatment variations and their impact on cardiovascular outcomes is crucial for optimizing MIS-C management.
Purpose of the Study:
- To characterize the variation in initial anakinra use for MIS-C across different treatment sites.
- To evaluate the association between early anakinra administration and short-term cardiovascular outcomes in children with MIS-C.
- To compare cardiovascular outcomes in patients receiving anakinra plus standard therapy versus standard therapy alone.
Main Methods:
- Retrospective cohort study of 1,516 MIS-C cases from a US surveillance registry (November 2020 - December 2021).
- Compared patients aged 2-20 years receiving anakinra plus intravenous immunoglobulin (IVIG) and/or glucocorticoids versus IVIG and/or glucocorticoids alone.
- Used inverse probability weighting to balance disease severity and analyzed vasopressor requirement, left ventricular ejection fraction, and C-reactive protein reduction.
Main Results:
- 13% of MIS-C patients received anakinra as initial treatment, with significant site-level variation (0-74%).
- Early anakinra addition was not associated with significant differences in vasopressor requirement (25.6% vs. 20.1%) or impaired left ventricular ejection fraction (33.7% vs. 25.7%).
- No significant difference was observed in C-reactive protein reduction on day 3.
Conclusions:
- Substantial variation exists in the initial use of anakinra for MIS-C in real-world clinical practice.
- Early administration of anakinra in conjunction with standard therapy (IVIG and/or glucocorticoids) did not demonstrate an average short-term improvement in cardiovascular outcomes for children with MIS-C.
- Further research may be needed to identify specific patient subgroups who might benefit from anakinra or to explore alternative treatment strategies.
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.
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