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Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. METHODS: We assessed effectiveness and safety of IL-6 bl...

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Autores principales: Somers, Emily C, Eschenauer, Gregory A, Troost, Jonathan P, Golob, Jonathan L, Gandhi, Tejal N, Wang, Lu, Zhou, Nina, Petty, Lindsay A, Baang, Ji Hoon, Dillman, Nicholas O, Frame, David, Gregg, Kevin S, Kaul, Dan R, Nagel, Jerod, Patel, Twisha S, Zhou, Shiwei, Lauring, Adam S, Hanauer, David A, Martin, Emily, Sharma, Pratima, Fung, Christopher M, Pogue, Jason M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454462/
https://www.ncbi.nlm.nih.gov/pubmed/32651997
http://dx.doi.org/10.1093/cid/ciaa954
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author Somers, Emily C
Eschenauer, Gregory A
Troost, Jonathan P
Golob, Jonathan L
Gandhi, Tejal N
Wang, Lu
Zhou, Nina
Petty, Lindsay A
Baang, Ji Hoon
Dillman, Nicholas O
Frame, David
Gregg, Kevin S
Kaul, Dan R
Nagel, Jerod
Patel, Twisha S
Zhou, Shiwei
Lauring, Adam S
Hanauer, David A
Martin, Emily
Sharma, Pratima
Fung, Christopher M
Pogue, Jason M
author_facet Somers, Emily C
Eschenauer, Gregory A
Troost, Jonathan P
Golob, Jonathan L
Gandhi, Tejal N
Wang, Lu
Zhou, Nina
Petty, Lindsay A
Baang, Ji Hoon
Dillman, Nicholas O
Frame, David
Gregg, Kevin S
Kaul, Dan R
Nagel, Jerod
Patel, Twisha S
Zhou, Shiwei
Lauring, Adam S
Hanauer, David A
Martin, Emily
Sharma, Pratima
Fung, Christopher M
Pogue, Jason M
author_sort Somers, Emily C
collection PubMed
description BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW). RESULTS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28–67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33–.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36–.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia. CONCLUSIONS: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.
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spelling pubmed-74544622020-08-31 Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19 Somers, Emily C Eschenauer, Gregory A Troost, Jonathan P Golob, Jonathan L Gandhi, Tejal N Wang, Lu Zhou, Nina Petty, Lindsay A Baang, Ji Hoon Dillman, Nicholas O Frame, David Gregg, Kevin S Kaul, Dan R Nagel, Jerod Patel, Twisha S Zhou, Shiwei Lauring, Adam S Hanauer, David A Martin, Emily Sharma, Pratima Fung, Christopher M Pogue, Jason M Clin Infect Dis Online Only Articles BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW). RESULTS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28–67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33–.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36–.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia. CONCLUSIONS: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence. Oxford University Press 2020-07-11 /pmc/articles/PMC7454462/ /pubmed/32651997 http://dx.doi.org/10.1093/cid/ciaa954 Text en © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Online Only Articles
Somers, Emily C
Eschenauer, Gregory A
Troost, Jonathan P
Golob, Jonathan L
Gandhi, Tejal N
Wang, Lu
Zhou, Nina
Petty, Lindsay A
Baang, Ji Hoon
Dillman, Nicholas O
Frame, David
Gregg, Kevin S
Kaul, Dan R
Nagel, Jerod
Patel, Twisha S
Zhou, Shiwei
Lauring, Adam S
Hanauer, David A
Martin, Emily
Sharma, Pratima
Fung, Christopher M
Pogue, Jason M
Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19
title Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19
title_full Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19
title_fullStr Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19
title_full_unstemmed Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19
title_short Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19
title_sort tocilizumab for treatment of mechanically ventilated patients with covid-19
topic Online Only Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454462/
https://www.ncbi.nlm.nih.gov/pubmed/32651997
http://dx.doi.org/10.1093/cid/ciaa954
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