Abstract:
Citation: Avsar FN, Kılıcaslan N, Sahutoglu T (2026) Comparative associations of Anakinra and Tocilizumab initiation with in-hospital mortality in severe COVID-19: A single-center sequential cohort study. PLoS One 21(9): e0357671. https://doi.org/10.1371/journal. pone.0357671
Editor: Benjamin M. Liu, Children's National Hospital, George Washington University, UNITED STATES OF AMERICA
Received:
June 18, 2026
Accepted:
August 19, 2026
Published:
September 2, 2026
Copyright: © 2026 Avsar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data availability statement : The data cannot be shared publicly because they derive from confidential hospital records and contain potentially identifying and sensitive patient information. Requests for a minimal de-identified
RESEARCH ARTICLE
Comparative associations of Anakinra and Tocilizumab initiation with in-hospital mortality in severe COVID-19: A single-center sequential cohort study
Fevzi Necati Avsar 1 , Nihat Kılıcaslan 2 , Tuncay Sahutoglu 3 *
1 Department of Internal Medicine, Sanliurfa Mehmet Akif Inan Training and Research Hospital, University of Health Sciences, Türkiye, 2 Department of Radiology, Sanliurfa Mehmet Akif Inan Training and Research Hospital, University of Health Sciences, Türkiye, 3 Division of Nephrology, Department of Internal Medicine, Sanliurfa Mehmet Akif Inan Training and Research Hospital, University of Health Sciences, Türkiye
[* tuncaysahutoglu@hotmail.com](mailto:tuncaysahutoglu@hotmail.com)
Abstract
Background
Interleukin-1 and interleukin-6 blockade have been widely used in severe COVID-19, but comparative real-world evidence regarding anakinra and tocilizumab in critically ill patients remains limited. We evaluated the associations of first initiation of anakinra or tocilizumab with 28-day and overall in-hospital mortality.
Methods
This single-center retrospective ICU cohort included adults with severe COVID-19. During hospital days 2-10, daily actions were classified as anakinra initiation, tocilizumab initiation, or control/defer. Calibrated overlap-weighted modified-Poisson models estimated associations with 28-day and overall in-hospital mortality; ferritin-adjusted sensitivity analyses were performed.
Results
Of 306 patients, 241 patients contributed 1,297 eligible person-days. Calibration met the prespecified balance criterion for the included covariates, although effective support for tocilizumab initiation remained limited. For 28-day in-hospital mortality, adjusted RRs versus control/defer were 0.99 (95% CI, 0.80-1.22) for anakinra and 0.99 (95% CI, 0.71-1.37) for tocilizumab. No clear associations were identified in the head-to-head comparison or for overall in-hospital mortality; ferritin-adjusted estimates were similar.
dataset should be sent to the Mehmet Akif Inan Training and Research Hospital Administration at sanliurfamaieah@saglik.gov.tr and copied to the corresponding author at tuncaysahutoglu@ hotmail.com, who will coordinate the access process. Access is subject to institutional approval and any required data-use agreement.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Conclusions
In this retrospective ICU cohort, neither..
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"abstract": "<jats:sec id=\"sec001\">\n <jats:title>Background</jats:title>\n <jats:p>Interleukin-1 and interleukin-6 blockade have been widely used in severe COVID-19, but comparative real-world evidence regarding anakinra and tocilizumab in critically ill patients remains limited. We evaluated the associations of first initiation of anakinra or tocilizumab with 28-day and overall in-hospital mortality.</jats:p>\n </jats:sec>\n <jats:sec id=\"sec002\">\n <jats:title>Methods</jats:title>\n <jats:p>This single-center retrospective ICU cohort included adults with severe COVID-19. During hospital days 2–10, daily actions were classified as anakinra initiation, tocilizumab initiation, or control/defer. Calibrated overlap-weighted modified-Poisson models estimated associations with 28-day and overall in-hospital mortality; ferritin-adjusted sensitivity analyses were performed.</jats:p>\n </jats:sec>\n <jats:sec id=\"sec003\">\n <jats:title>Results</jats:title>\n <jats:p>Of 306 patients, 241 patients contributed 1,297 eligible person-days. Calibration met the prespecified balance criterion for the included covariates, although effective support for tocilizumab initiation remained limited. For 28-day in-hospital mortality, adjusted RRs versus control/defer were 0.99 (95% CI, 0.80–1.22) for anakinra and 0.99 (95% CI, 0.71–1.37) for tocilizumab. No clear associations were identified in the head-to-head comparison or for overall in-hospital mortality; ferritin-adjusted estimates were similar.</jats:p>\n </jats:sec>\n <jats:sec id=\"sec004\">\n <jats:title>Conclusions</jats:title>\n <jats:p>In this retrospective ICU cohort, neither anakinra nor tocilizumab initiation showed a clear association with 28-day or overall in-hospital mortality. Estimates were imprecise, particularly for tocilizumab, and remain susceptible to residual confounding.</jats:p>\n </jats:sec>",
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