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

Authors

Joyce C. Chang, Division of Immunology, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
Cameron C. Young, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts.
Eyal Muscal, Division of Rheumatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Sara K. Sexson Tejtel, Division of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Fetal Center, Houston, Texas.
Margaret M. Newhams, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts.
Suden Kucukak, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts.
Hillary Crandall, Division of Pediatric Critical Care, Department of Pediatrics, University of Utah and Primary Children's Hospital, Salt Lake City, Utah.
Aline B. Maddux, Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora.
Courtney M. Rowan, Division of Pediatric Critical Care Medicine and Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis.
Natasha B. Halasa, Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
Helen A. Harvey, Department of Critical Care Medicine, Rady Children's Hospital-San Diego, San Diego, California.
Charlotte V. Hobbs, Division of Infectious Disease, Department of Pediatrics, University of Mississippi Medical Center, Jackson.
Mark W. Hall, Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio.
Michele Kong, Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham.
Cassyanne L. Aguiar, Department of Pediatric Rheumatology, Children's Hospital of The King's Daughters, Eastern Virginia Medical School, Norfolk.
Jennifer E. Schuster, Division of Pediatric Infectious Disease, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri.
Julie C. Fitzgerald, Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Aalok R. Singh, Pediatric Critical Care Division, Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College, Valhalla, New York.Follow
Kari Wellnitz, Division of Pediatric Critical Care, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City.
Ryan A. Nofziger, Division of Critical Care Medicine, Akron Children's Hospital, Akron, Ohio.
Natalie Z. Cvijanovich, Division of Critical Care Medicine, UCSF Benioff Children's Hospital Oakland, Oakland, California.
Elizabeth H. Mack, Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston.
Adam J. Schwarz, Division of Critical Care Medicine, Children's Hospital Orange County, Orange, California.
Sabrina M. Heidemann, Division of Pediatric Critical Care Medicine, Children's Hospital of Michigan, Central Michigan University, Detroit.
Jane W. Newburger, Department of Cardiology, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
Laura D. Zambrano, CDC COVID-19 Response Team, Atlanta, Georgia.
Angela P. Campbell, CDC COVID-19 Response Team, Atlanta, Georgia.
Manish M. Patel, CDC COVID-19 Response Team, Atlanta, Georgia.Follow
Adrienne G. Randolph, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, and Departments of Pediatrics and Anaesthesia, Harvard Medical School, Boston, Massachusetts.
Mary Beth Son, Division of Immunology, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.

Author Type(s)

Faculty

DOI

10.1002/art.42495

Journal Title

Arthritis & Rheumatology

First Page

1466

Last Page

1476

Document Type

Article

Publication Date

8-1-2023

Department

Pediatrics

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.

Recommended Citation

Chang, J. C., Young, C. C., Muscal, E., Sexson Tejtel, S. K., Newhams, M. M., Kucukak, S., Crandall, H., Maddux, A. B., Rowan, C. M., Halasa, N. B., Harvey, H. A., Hobbs, C. V., Hall, M. W., Kong, M., Aguiar, C. L., Schuster, J. E., Fitzgerald, J. C., Singh, A. R., Wellnitz, K., Nofziger, R. A., Cvijanovich, N. Z., Mack, E. H., Schwarz, A. J., Heidemann, S. M., Newburger, J. W., Zambrano, L. D., Campbell, A. P., Patel, M. M., Randolph, A. G., & Son, M. B. (2023). Variation in Early Anakinra Use and Short-Term Outcomes in Multisystem Inflammatory Syndrome in Children. Arthritis & Rheumatology, 75 (8), 1466-1476. https://doi.org/10.1002/art.42495