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Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study

BACKGROUND: Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients re...

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Autores principales: Biran, Noa, Ip, Andrew, Ahn, Jaeil, Go, Ronaldo C, Wang, Shuqi, Mathura, Shivam, Sinclaire, Brittany A, Bednarz, Urszula, Marafelias, Michael, Hansen, Eric, Siegel, David S, Goy, Andre H, Pecora, Andrew L, Sawczuk, Ihor S, Koniaris, Lauren S, Simwenyi, Micky, Varga, Daniel W, Tank, Lisa K, Stein, Aaron A, Allusson, Valerie, Lin, George S, Oser, William F, Tuma, Roman A, Reichman, Joseph, Brusco, Louis, Carpenter, Kim L, Costanzo, Eric J, Vivona, Vincent, Goldberg, Stuart L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428303/
https://www.ncbi.nlm.nih.gov/pubmed/32838323
http://dx.doi.org/10.1016/S2665-9913(20)30277-0
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author Biran, Noa
Ip, Andrew
Ahn, Jaeil
Go, Ronaldo C
Wang, Shuqi
Mathura, Shivam
Sinclaire, Brittany A
Bednarz, Urszula
Marafelias, Michael
Hansen, Eric
Siegel, David S
Goy, Andre H
Pecora, Andrew L
Sawczuk, Ihor S
Koniaris, Lauren S
Simwenyi, Micky
Varga, Daniel W
Tank, Lisa K
Stein, Aaron A
Allusson, Valerie
Lin, George S
Oser, William F
Tuma, Roman A
Reichman, Joseph
Brusco, Louis
Carpenter, Kim L
Costanzo, Eric J
Vivona, Vincent
Goldberg, Stuart L
author_facet Biran, Noa
Ip, Andrew
Ahn, Jaeil
Go, Ronaldo C
Wang, Shuqi
Mathura, Shivam
Sinclaire, Brittany A
Bednarz, Urszula
Marafelias, Michael
Hansen, Eric
Siegel, David S
Goy, Andre H
Pecora, Andrew L
Sawczuk, Ihor S
Koniaris, Lauren S
Simwenyi, Micky
Varga, Daniel W
Tank, Lisa K
Stein, Aaron A
Allusson, Valerie
Lin, George S
Oser, William F
Tuma, Roman A
Reichman, Joseph
Brusco, Louis
Carpenter, Kim L
Costanzo, Eric J
Vivona, Vincent
Goldberg, Stuart L
author_sort Biran, Noa
collection PubMed
description BACKGROUND: Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19. METHODS: We did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA). We included patients (aged ≥18 years) with laboratory-confirmed COVID-19 who needed support in the ICU. We obtained data from a prospective observational database and compared outcomes in patients who received tocilizumab with those who did not. We applied a multivariable Cox model with propensity score matching to reduce confounding effects. The primary endpoint was hospital-related mortality. The prospective observational database is registered on ClinicalTrials.gov, NCT04347993. FINDINGS: Between March 1 and April 22, 2020, 764 patients with COVID-19 required support in the ICU, of whom 210 (27%) received tocilizumab. Factors associated with receiving tocilizumab were patients' age, gender, renal function, and treatment location. 630 patients were included in the propensity score-matched population, of whom 210 received tocilizumab and 420 did not receive tocilizumab. 358 (57%) of 630 patients died, 102 (49%) who received tocilizumab and 256 (61%) who did not receive tocilizumab. Overall median survival from time of admission was not reached (95% CI 23 days–not reached) among patients receiving tocilizumab and was 19 days (16–26) for those who did not receive tocilizumab (hazard ratio [HR] 0·71, 95% CI 0·56–0·89; p=0·0027). In the primary multivariable Cox regression analysis with propensity matching, an association was noted between receiving tocilizumab and decreased hospital-related mortality (HR 0·64, 95% CI 0·47–0·87; p=0·0040). Similar associations with tocilizumab were noted among subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of 15 mg/dL or higher. INTERPRETATION: In this observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. Results of ongoing randomised controlled trials are awaited. FUNDING: None.
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spelling pubmed-74283032020-08-16 Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study Biran, Noa Ip, Andrew Ahn, Jaeil Go, Ronaldo C Wang, Shuqi Mathura, Shivam Sinclaire, Brittany A Bednarz, Urszula Marafelias, Michael Hansen, Eric Siegel, David S Goy, Andre H Pecora, Andrew L Sawczuk, Ihor S Koniaris, Lauren S Simwenyi, Micky Varga, Daniel W Tank, Lisa K Stein, Aaron A Allusson, Valerie Lin, George S Oser, William F Tuma, Roman A Reichman, Joseph Brusco, Louis Carpenter, Kim L Costanzo, Eric J Vivona, Vincent Goldberg, Stuart L Lancet Rheumatol Articles BACKGROUND: Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19. METHODS: We did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA). We included patients (aged ≥18 years) with laboratory-confirmed COVID-19 who needed support in the ICU. We obtained data from a prospective observational database and compared outcomes in patients who received tocilizumab with those who did not. We applied a multivariable Cox model with propensity score matching to reduce confounding effects. The primary endpoint was hospital-related mortality. The prospective observational database is registered on ClinicalTrials.gov, NCT04347993. FINDINGS: Between March 1 and April 22, 2020, 764 patients with COVID-19 required support in the ICU, of whom 210 (27%) received tocilizumab. Factors associated with receiving tocilizumab were patients' age, gender, renal function, and treatment location. 630 patients were included in the propensity score-matched population, of whom 210 received tocilizumab and 420 did not receive tocilizumab. 358 (57%) of 630 patients died, 102 (49%) who received tocilizumab and 256 (61%) who did not receive tocilizumab. Overall median survival from time of admission was not reached (95% CI 23 days–not reached) among patients receiving tocilizumab and was 19 days (16–26) for those who did not receive tocilizumab (hazard ratio [HR] 0·71, 95% CI 0·56–0·89; p=0·0027). In the primary multivariable Cox regression analysis with propensity matching, an association was noted between receiving tocilizumab and decreased hospital-related mortality (HR 0·64, 95% CI 0·47–0·87; p=0·0040). Similar associations with tocilizumab were noted among subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of 15 mg/dL or higher. INTERPRETATION: In this observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. Results of ongoing randomised controlled trials are awaited. FUNDING: None. Elsevier Ltd. 2020-10 2020-08-14 /pmc/articles/PMC7428303/ /pubmed/32838323 http://dx.doi.org/10.1016/S2665-9913(20)30277-0 Text en © 2020 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Articles
Biran, Noa
Ip, Andrew
Ahn, Jaeil
Go, Ronaldo C
Wang, Shuqi
Mathura, Shivam
Sinclaire, Brittany A
Bednarz, Urszula
Marafelias, Michael
Hansen, Eric
Siegel, David S
Goy, Andre H
Pecora, Andrew L
Sawczuk, Ihor S
Koniaris, Lauren S
Simwenyi, Micky
Varga, Daniel W
Tank, Lisa K
Stein, Aaron A
Allusson, Valerie
Lin, George S
Oser, William F
Tuma, Roman A
Reichman, Joseph
Brusco, Louis
Carpenter, Kim L
Costanzo, Eric J
Vivona, Vincent
Goldberg, Stuart L
Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
title Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
title_full Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
title_fullStr Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
title_full_unstemmed Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
title_short Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
title_sort tocilizumab among patients with covid-19 in the intensive care unit: a multicentre observational study
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428303/
https://www.ncbi.nlm.nih.gov/pubmed/32838323
http://dx.doi.org/10.1016/S2665-9913(20)30277-0
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