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Tocilizumab and steroid treatment in patients with COVID-19 pneumonia

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVI...

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Autores principales: Mikulska, Malgorzata, Nicolini, Laura Ambra, Signori, Alessio, Di Biagio, Antonio, Sepulcri, Chiara, Russo, Chiara, Dettori, Silvia, Berruti, Marco, Sormani, Maria Pia, Giacobbe, Daniele Roberto, Vena, Antonio, De Maria, Andrea, Dentone, Chiara, Taramasso, Lucia, Mirabella, Michele, Magnasco, Laura, Mora, Sara, Delfino, Emanuele, Toscanini, Federica, Balletto, Elisa, Alessandrini, Anna Ida, Baldi, Federico, Briano, Federica, Camera, Marco, Dodi, Ferdinando, Ferrazin, Antonio, Labate, Laura, Mazzarello, Giovanni, Pincino, Rachele, Portunato, Federica, Tutino, Stefania, Barisione, Emanuela, Bruzzone, Bianca, Orsi, Andrea, Schenone, Eva, Rosseti, Nirmala, Sasso, Elisabetta, Da Rin, Giorgio, Pelosi, Paolo, Beltramini, Sabrina, Giacomini, Mauro, Icardi, Giancarlo, Gratarola, Angelo, Bassetti, Matteo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440633/
https://www.ncbi.nlm.nih.gov/pubmed/32817707
http://dx.doi.org/10.1371/journal.pone.0237831
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author Mikulska, Malgorzata
Nicolini, Laura Ambra
Signori, Alessio
Di Biagio, Antonio
Sepulcri, Chiara
Russo, Chiara
Dettori, Silvia
Berruti, Marco
Sormani, Maria Pia
Giacobbe, Daniele Roberto
Vena, Antonio
De Maria, Andrea
Dentone, Chiara
Taramasso, Lucia
Mirabella, Michele
Magnasco, Laura
Mora, Sara
Delfino, Emanuele
Toscanini, Federica
Balletto, Elisa
Alessandrini, Anna Ida
Baldi, Federico
Briano, Federica
Camera, Marco
Dodi, Ferdinando
Ferrazin, Antonio
Labate, Laura
Mazzarello, Giovanni
Pincino, Rachele
Portunato, Federica
Tutino, Stefania
Barisione, Emanuela
Bruzzone, Bianca
Orsi, Andrea
Schenone, Eva
Rosseti, Nirmala
Sasso, Elisabetta
Da Rin, Giorgio
Pelosi, Paolo
Beltramini, Sabrina
Giacomini, Mauro
Icardi, Giancarlo
Gratarola, Angelo
Bassetti, Matteo
author_facet Mikulska, Malgorzata
Nicolini, Laura Ambra
Signori, Alessio
Di Biagio, Antonio
Sepulcri, Chiara
Russo, Chiara
Dettori, Silvia
Berruti, Marco
Sormani, Maria Pia
Giacobbe, Daniele Roberto
Vena, Antonio
De Maria, Andrea
Dentone, Chiara
Taramasso, Lucia
Mirabella, Michele
Magnasco, Laura
Mora, Sara
Delfino, Emanuele
Toscanini, Federica
Balletto, Elisa
Alessandrini, Anna Ida
Baldi, Federico
Briano, Federica
Camera, Marco
Dodi, Ferdinando
Ferrazin, Antonio
Labate, Laura
Mazzarello, Giovanni
Pincino, Rachele
Portunato, Federica
Tutino, Stefania
Barisione, Emanuela
Bruzzone, Bianca
Orsi, Andrea
Schenone, Eva
Rosseti, Nirmala
Sasso, Elisabetta
Da Rin, Giorgio
Pelosi, Paolo
Beltramini, Sabrina
Giacomini, Mauro
Icardi, Giancarlo
Gratarola, Angelo
Bassetti, Matteo
author_sort Mikulska, Malgorzata
collection PubMed
description INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24(th), also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HR(OW)). RESULTS: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30–100) and median PaO(2)/FiO(2) 200 mmHg (IQR 133–289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8–86.7) vs. 64.1% (95%CI, 51.3–74.0), HR(OW) 0.48, 95%CI, 0.23–0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7–92.6) vs. 71.9% (95%CI, 46–73), HR(OW) 0.41, 95%CI: 0.19–0.89, p = 0.025. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.
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spelling pubmed-74406332020-08-26 Tocilizumab and steroid treatment in patients with COVID-19 pneumonia Mikulska, Malgorzata Nicolini, Laura Ambra Signori, Alessio Di Biagio, Antonio Sepulcri, Chiara Russo, Chiara Dettori, Silvia Berruti, Marco Sormani, Maria Pia Giacobbe, Daniele Roberto Vena, Antonio De Maria, Andrea Dentone, Chiara Taramasso, Lucia Mirabella, Michele Magnasco, Laura Mora, Sara Delfino, Emanuele Toscanini, Federica Balletto, Elisa Alessandrini, Anna Ida Baldi, Federico Briano, Federica Camera, Marco Dodi, Ferdinando Ferrazin, Antonio Labate, Laura Mazzarello, Giovanni Pincino, Rachele Portunato, Federica Tutino, Stefania Barisione, Emanuela Bruzzone, Bianca Orsi, Andrea Schenone, Eva Rosseti, Nirmala Sasso, Elisabetta Da Rin, Giorgio Pelosi, Paolo Beltramini, Sabrina Giacomini, Mauro Icardi, Giancarlo Gratarola, Angelo Bassetti, Matteo PLoS One Research Article INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24(th), also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HR(OW)). RESULTS: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30–100) and median PaO(2)/FiO(2) 200 mmHg (IQR 133–289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8–86.7) vs. 64.1% (95%CI, 51.3–74.0), HR(OW) 0.48, 95%CI, 0.23–0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7–92.6) vs. 71.9% (95%CI, 46–73), HR(OW) 0.41, 95%CI: 0.19–0.89, p = 0.025. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia. Public Library of Science 2020-08-20 /pmc/articles/PMC7440633/ /pubmed/32817707 http://dx.doi.org/10.1371/journal.pone.0237831 Text en © 2020 Mikulska et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mikulska, Malgorzata
Nicolini, Laura Ambra
Signori, Alessio
Di Biagio, Antonio
Sepulcri, Chiara
Russo, Chiara
Dettori, Silvia
Berruti, Marco
Sormani, Maria Pia
Giacobbe, Daniele Roberto
Vena, Antonio
De Maria, Andrea
Dentone, Chiara
Taramasso, Lucia
Mirabella, Michele
Magnasco, Laura
Mora, Sara
Delfino, Emanuele
Toscanini, Federica
Balletto, Elisa
Alessandrini, Anna Ida
Baldi, Federico
Briano, Federica
Camera, Marco
Dodi, Ferdinando
Ferrazin, Antonio
Labate, Laura
Mazzarello, Giovanni
Pincino, Rachele
Portunato, Federica
Tutino, Stefania
Barisione, Emanuela
Bruzzone, Bianca
Orsi, Andrea
Schenone, Eva
Rosseti, Nirmala
Sasso, Elisabetta
Da Rin, Giorgio
Pelosi, Paolo
Beltramini, Sabrina
Giacomini, Mauro
Icardi, Giancarlo
Gratarola, Angelo
Bassetti, Matteo
Tocilizumab and steroid treatment in patients with COVID-19 pneumonia
title Tocilizumab and steroid treatment in patients with COVID-19 pneumonia
title_full Tocilizumab and steroid treatment in patients with COVID-19 pneumonia
title_fullStr Tocilizumab and steroid treatment in patients with COVID-19 pneumonia
title_full_unstemmed Tocilizumab and steroid treatment in patients with COVID-19 pneumonia
title_short Tocilizumab and steroid treatment in patients with COVID-19 pneumonia
title_sort tocilizumab and steroid treatment in patients with covid-19 pneumonia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440633/
https://www.ncbi.nlm.nih.gov/pubmed/32817707
http://dx.doi.org/10.1371/journal.pone.0237831
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