Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial

OBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumoni...

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Autores: Tom, Jennifer, Bao, Min, Tsai, Larry, Qamra, Aditi, Summers, David, Carrasco Triguero, Montserrat, Mcbride, Jacqueline, Rosenberger, Carrie M., Lin, Celia J. F., Stubbings, William, Blyth, Kevin G., Carratalà, Jordi, François, Bruno, Benfield, Thomas, Haslem, Derrick, Bonfanti, Paolo, Van der Leest, Cor H., Rohatgi, Nidhi, Wiese, Lothar, Luyt, Charles Edouard, Kheradmand, Farrah, Rosas, Ivan O., Cai, Fang
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/184279
Acceso en línea:https://hdl.handle.net/2445/184279
Access Level:acceso abierto
Palabra clave:COVID-19
Marcadors bioquímics
Biochemical markers
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spelling Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled TrialTom, JenniferBao, MinTsai, LarryQamra, AditiSummers, DavidCarrasco Triguero, MontserratMcbride, JacquelineRosenberger, Carrie M.Lin, Celia J. F.Stubbings, WilliamBlyth, Kevin G.Carratalà, JordiFrançois, BrunoBenfield, ThomasHaslem, DerrickBonfanti, PaoloVan der Leest, Cor H.Rohatgi, NidhiWiese, LotharLuyt, Charles EdouardKheradmand, FarrahRosas, Ivan O.Cai, FangCOVID-19Marcadors bioquímicsCOVID-19Biochemical markersOBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumonia after treatment with tocilizumab, an anti-interleukin-6 receptor antibody, using data from the COVACTA trial in patients hospitalized with severe coronavirus disease 2019 pneumonia. DESIGN: Exploratory analysis from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. SETTING: Hospitals in North America and Europe. PATIENTS: Adults hospitalized with severe coronavirus disease 2019 pneumonia receiving standard care. INTERVENTION: Randomly assigned 2:1 to IV tocilizumab 8 mg/kg or placebo. MEASUREMENTS AND MAIN RESULTS: Candidate biomarkers were measured in 295 patients in the tocilizumab arm and 142 patients in the placebo arm. Efficacy outcomes assessed were clinical status on a seven-category ordinal scale (1, discharge; 7, death), mortality, time to hospital discharge, and mechanical ventilation (if not receiving it at randomization) through day 28. Prognostic and predictive biomarkers were evaluated continuously with proportional odds, binomial or Fine-Gray models, and additional sensitivity analyses. Modeling in the placebo arm showed all candidate biomarkers except lactate dehydrogenase and d-dimer were strongly prognostic for day 28 clinical outcomes of mortality, mechanical ventilation, clinical status, and time to hospital discharge. Modeling in the tocilizumab arm showed a predictive value of ferritin for day 28 clinical outcomes of mortality (predictive interaction, p = 0.03), mechanical ventilation (predictive interaction, p = 0.01), and clinical status (predictive interaction, p = 0.02) compared with placebo. CONCLUSIONS: Multiple biomarkers prognostic for clinical outcomes were confirmed in COVACTA. Ferritin was identified as a predictive biomarker for the effects of tocilizumab in the COVACTA patient population; high ferritin levels were associated with better clinical outcomes for tocilizumab compared with placebo at day 28.Ovid Technologies (Wolters Kluwer Health)2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/184279Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1097/CCM.0000000000005229Critical Care Medicine, 2021, vol 50, num 3, p. 398-409https://doi.org/10.1097/CCM.0000000000005229cc by-nc-nd (c) Tom, Jennifer et al, 2022http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1842792026-05-27T06:46:51Z
dc.title.none.fl_str_mv Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial
title Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial
spellingShingle Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial
Tom, Jennifer
COVID-19
Marcadors bioquímics
COVID-19
Biochemical markers
title_short Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial
title_full Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial
title_fullStr Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial
title_full_unstemmed Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial
title_sort Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial
dc.creator.none.fl_str_mv Tom, Jennifer
Bao, Min
Tsai, Larry
Qamra, Aditi
Summers, David
Carrasco Triguero, Montserrat
Mcbride, Jacqueline
Rosenberger, Carrie M.
Lin, Celia J. F.
Stubbings, William
Blyth, Kevin G.
Carratalà, Jordi
François, Bruno
Benfield, Thomas
Haslem, Derrick
Bonfanti, Paolo
Van der Leest, Cor H.
Rohatgi, Nidhi
Wiese, Lothar
Luyt, Charles Edouard
Kheradmand, Farrah
Rosas, Ivan O.
Cai, Fang
author Tom, Jennifer
author_facet Tom, Jennifer
Bao, Min
Tsai, Larry
Qamra, Aditi
Summers, David
Carrasco Triguero, Montserrat
Mcbride, Jacqueline
Rosenberger, Carrie M.
Lin, Celia J. F.
Stubbings, William
Blyth, Kevin G.
Carratalà, Jordi
François, Bruno
Benfield, Thomas
Haslem, Derrick
Bonfanti, Paolo
Van der Leest, Cor H.
Rohatgi, Nidhi
Wiese, Lothar
Luyt, Charles Edouard
Kheradmand, Farrah
Rosas, Ivan O.
Cai, Fang
author_role author
author2 Bao, Min
Tsai, Larry
Qamra, Aditi
Summers, David
Carrasco Triguero, Montserrat
Mcbride, Jacqueline
Rosenberger, Carrie M.
Lin, Celia J. F.
Stubbings, William
Blyth, Kevin G.
Carratalà, Jordi
François, Bruno
Benfield, Thomas
Haslem, Derrick
Bonfanti, Paolo
Van der Leest, Cor H.
Rohatgi, Nidhi
Wiese, Lothar
Luyt, Charles Edouard
Kheradmand, Farrah
Rosas, Ivan O.
Cai, Fang
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COVID-19
Marcadors bioquímics
COVID-19
Biochemical markers
topic COVID-19
Marcadors bioquímics
COVID-19
Biochemical markers
description OBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumonia after treatment with tocilizumab, an anti-interleukin-6 receptor antibody, using data from the COVACTA trial in patients hospitalized with severe coronavirus disease 2019 pneumonia. DESIGN: Exploratory analysis from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. SETTING: Hospitals in North America and Europe. PATIENTS: Adults hospitalized with severe coronavirus disease 2019 pneumonia receiving standard care. INTERVENTION: Randomly assigned 2:1 to IV tocilizumab 8 mg/kg or placebo. MEASUREMENTS AND MAIN RESULTS: Candidate biomarkers were measured in 295 patients in the tocilizumab arm and 142 patients in the placebo arm. Efficacy outcomes assessed were clinical status on a seven-category ordinal scale (1, discharge; 7, death), mortality, time to hospital discharge, and mechanical ventilation (if not receiving it at randomization) through day 28. Prognostic and predictive biomarkers were evaluated continuously with proportional odds, binomial or Fine-Gray models, and additional sensitivity analyses. Modeling in the placebo arm showed all candidate biomarkers except lactate dehydrogenase and d-dimer were strongly prognostic for day 28 clinical outcomes of mortality, mechanical ventilation, clinical status, and time to hospital discharge. Modeling in the tocilizumab arm showed a predictive value of ferritin for day 28 clinical outcomes of mortality (predictive interaction, p = 0.03), mechanical ventilation (predictive interaction, p = 0.01), and clinical status (predictive interaction, p = 0.02) compared with placebo. CONCLUSIONS: Multiple biomarkers prognostic for clinical outcomes were confirmed in COVACTA. Ferritin was identified as a predictive biomarker for the effects of tocilizumab in the COVACTA patient population; high ferritin levels were associated with better clinical outcomes for tocilizumab compared with placebo at day 28.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/184279
url https://hdl.handle.net/2445/184279
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1097/CCM.0000000000005229
Critical Care Medicine, 2021, vol 50, num 3, p. 398-409
https://doi.org/10.1097/CCM.0000000000005229
dc.rights.none.fl_str_mv cc by-nc-nd (c) Tom, Jennifer et al, 2022
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Tom, Jennifer et al, 2022
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Ovid Technologies (Wolters Kluwer Health)
publisher.none.fl_str_mv Ovid Technologies (Wolters Kluwer Health)
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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