Tocilizumab and steroid treatment in patients with COVID-19 pneumonia

Malgorzata Mikulska; Laura Ambra Nicolini; Alessio Signori; Antonio Di Biagio; Chiara Sepulcri; Chiara Russo; Silvia Dettori; Marco Berruti; Maria Pia Sormani; Daniele Roberto Giacobbe; Antonio Vena; Andrea De Maria; Chiara Dentone; Lucia Taramasso; Michele Mirabella; Laura Magnasco; Sara Mora; Emanuele Delfino; Federica Toscanini; Elisa Balletto; Anna Ida Alessandrini; Federico Baldi; Federica Briano; Marco Camera; Ferdinando Dodi; Antonio Ferrazin; Laura Labate; Giovanni Mazzarello; Rachele Pincino; Federica Portunato; Stefania Tutino; Emanuela Barisione; Bianca Bruzzone; Andrea Orsi; Eva Schenone; Nirmala Rosseti; Elisabetta Sasso; Giorgio Da Rin; Paolo Pelosi; Sabrina Beltramini; Mauro Giacomini; Giancarlo Icardi; Angelo Gratarola; Matteo Bassetti

doi:10.1371/journal.pone.0237831

Tocilizumab and steroid treatment in patients with COVID-19 pneumonia

Malgorzata Mikulska, Laura Ambra Nicolini, Alessio Signori, Antonio Di Biagio, Chiara Sepulcri, Chiara Russo, Silvia Dettori, Marco Berruti, Maria Pia Sormani, Daniele Roberto Giacobbe, Antonio Vena, Andrea De Maria, Chiara Dentone, Lucia Taramasso, Michele Mirabella, Laura Magnasco, Sara Mora, Emanuele Delfino, Federica Toscanini, Elisa BallettoAnna Ida Alessandrini, Federico Baldi, Federica Briano, Marco Camera, Ferdinando Dodi, Antonio Ferrazin, Laura Labate, Giovanni Mazzarello, Rachele Pincino, Federica Portunato, Stefania Tutino, Emanuela Barisione, Bianca Bruzzone, Andrea Orsi, Eva Schenone, Nirmala Rosseti, Elisabetta Sasso, Giorgio Da Rin, Paolo Pelosi, Sabrina Beltramini, Mauro Giacomini, Giancarlo Icardi, Angelo Gratarola, Matteo Bassetti

Research output: Contribution to journal › Article › peer-review

Abstract

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 24th, 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 (HROW). 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 PaO2/FiO2 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), HROW 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), HROW 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.

Original language	English
Article number	e0237831
Journal	PLoS One
Volume	15
Issue number	8 August
DOIs	https://doi.org/10.1371/journal.pone.0237831
Publication status	Published - Aug 2020

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

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Mikulska, M., Nicolini, L. A., Signori, A., Di Biagio, A., Sepulcri, C., Russo, C., Dettori, S., Berruti, M., Sormani, M. P., Giacobbe, D. R., Vena, A., De Maria, A., Dentone, C., Taramasso, L., Mirabella, M., Magnasco, L., Mora, S., Delfino, E., Toscanini, F., ... Bassetti, M. (2020). Tocilizumab and steroid treatment in patients with COVID-19 pneumonia. PLoS One, 15(8 August), [e0237831]. https://doi.org/10.1371/journal.pone.0237831

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; Rin, Giorgio Da; Pelosi, Paolo; Beltramini, Sabrina; Giacomini, Mauro; Icardi, Giancarlo; Gratarola, Angelo; Bassetti, Matteo.

In: PLoS One, Vol. 15, No. 8 August, e0237831, 08.2020.

Research output: Contribution to journal › Article › peer-review

Mikulska, M , Nicolini, LA, Signori, A, Di Biagio, A, Sepulcri, C, Russo, C, Dettori, S, Berruti, M, Sormani, MP, Giacobbe, DR, Vena, A, De Maria, A, Dentone, C, Taramasso, L, Mirabella, M, Magnasco, L, Mora, S, Delfino, E, Toscanini, F, Balletto, E, Alessandrini, AI, Baldi, F, Briano, F, Camera, M, Dodi, F, Ferrazin, A, Labate, L, Mazzarello, G, Pincino, R, Portunato, F, Tutino, S, Barisione, E, Bruzzone, B, Orsi, A, Schenone, E, Rosseti, N, Sasso, E, Rin, GD, Pelosi, P, Beltramini, S, Giacomini, M, Icardi, G, Gratarola, A & Bassetti, M 2020, 'Tocilizumab and steroid treatment in patients with COVID-19 pneumonia', PLoS One, vol. 15, no. 8 August, e0237831. https://doi.org/10.1371/journal.pone.0237831

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 ; Rin, Giorgio Da ; Pelosi, Paolo ; Beltramini, Sabrina ; Giacomini, Mauro ; Icardi, Giancarlo ; Gratarola, Angelo ; Bassetti, Matteo. / Tocilizumab and steroid treatment in patients with COVID-19 pneumonia. In: PLoS One. 2020 ; Vol. 15, No. 8 August.

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title = "Tocilizumab and steroid treatment in patients with COVID-19 pneumonia",

abstract = "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 24th, 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 (HROW). 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 PaO2/FiO2 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), HROW 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), HROW 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.",

author = "Malgorzata Mikulska and Nicolini, {Laura Ambra} and Alessio Signori and {Di Biagio}, Antonio and Chiara Sepulcri and Chiara Russo and Silvia Dettori and Marco Berruti and Sormani, {Maria Pia} and Giacobbe, {Daniele Roberto} and Antonio Vena and {De Maria}, Andrea and Chiara Dentone and Lucia Taramasso and Michele Mirabella and Laura Magnasco and Sara Mora and Emanuele Delfino and Federica Toscanini and Elisa Balletto and Alessandrini, {Anna Ida} and Federico Baldi and Federica Briano and Marco Camera and Ferdinando Dodi and Antonio Ferrazin and Laura Labate and Giovanni Mazzarello and Rachele Pincino and Federica Portunato and Stefania Tutino and Emanuela Barisione and Bianca Bruzzone and Andrea Orsi and Eva Schenone and Nirmala Rosseti and Elisabetta Sasso and Rin, {Giorgio Da} and Paolo Pelosi and Sabrina Beltramini and Mauro Giacomini and Giancarlo Icardi and Angelo Gratarola and Matteo Bassetti",

year = "2020",

month = aug,

doi = "10.1371/journal.pone.0237831",

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TY - JOUR

T1 - Tocilizumab and steroid treatment in patients with COVID-19 pneumonia

AU - Mikulska, Malgorzata

AU - Nicolini, Laura Ambra

AU - Signori, Alessio

AU - Di Biagio, Antonio

AU - Sepulcri, Chiara

AU - Russo, Chiara

AU - Dettori, Silvia

AU - Berruti, Marco

AU - Sormani, Maria Pia

AU - Giacobbe, Daniele Roberto

AU - Vena, Antonio

AU - De Maria, Andrea

AU - Dentone, Chiara

AU - Taramasso, Lucia

AU - Mirabella, Michele

AU - Magnasco, Laura

AU - Mora, Sara

AU - Delfino, Emanuele

AU - Toscanini, Federica

AU - Balletto, Elisa

AU - Alessandrini, Anna Ida

AU - Baldi, Federico

AU - Briano, Federica

AU - Camera, Marco

AU - Dodi, Ferdinando

AU - Ferrazin, Antonio

AU - Labate, Laura

AU - Mazzarello, Giovanni

AU - Pincino, Rachele

AU - Portunato, Federica

AU - Tutino, Stefania

AU - Barisione, Emanuela

AU - Bruzzone, Bianca

AU - Orsi, Andrea

AU - Schenone, Eva

AU - Rosseti, Nirmala

AU - Sasso, Elisabetta

AU - Rin, Giorgio Da

AU - Pelosi, Paolo

AU - Beltramini, Sabrina

AU - Giacomini, Mauro

AU - Icardi, Giancarlo

AU - Gratarola, Angelo

AU - Bassetti, Matteo

PY - 2020/8

Y1 - 2020/8

N2 - 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 24th, 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 (HROW). 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 PaO2/FiO2 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), HROW 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), HROW 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.

AB - 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 24th, 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 (HROW). 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 PaO2/FiO2 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), HROW 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), HROW 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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