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

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Harvard

Tom, J, Bao, M, Tsai, L, Qamra, A, Summers, D, Carrasco-Triguero, M, McBride, J, Rosenberger, CM, Lin, CJF, Stubbings, W, Blyth, KG, Carratalà, J, François, B, Benfield, T, Haslem, D, Bonfanti, P, van der Leest, CH, Rohatgi, N, Wiese, L, Luyt, CE, Kheradmand, F, Rosas, IO & Cai, F 2021, 'Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial', Critical Care Medicine. https://doi.org/10.1097/CCM.0000000000005229

APA

Tom, J., Bao, M., Tsai, L., Qamra, A., Summers, D., Carrasco-Triguero, M., McBride, J., Rosenberger, C. M., Lin, C. J. F., Stubbings, W., Blyth, K. G., Carratalà, J., François, B., Benfield, T., Haslem, D., Bonfanti, P., van der Leest, C. H., Rohatgi, N., Wiese, L., ... Cai, F. (2021). Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial. Critical Care Medicine. https://doi.org/10.1097/CCM.0000000000005229

CBE

Tom J, Bao M, Tsai L, Qamra A, Summers D, Carrasco-Triguero M, McBride J, Rosenberger CM, Lin CJF, Stubbings W, Blyth KG, Carratalà J, François B, Benfield T, Haslem D, Bonfanti P, van der Leest CH, Rohatgi N, Wiese L, Luyt CE, Kheradmand F, Rosas IO, Cai F. 2021. Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial. Critical Care Medicine. https://doi.org/10.1097/CCM.0000000000005229

MLA

Vancouver

Author

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. / Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial. I: Critical Care Medicine. 2021.

Bibtex

@article{1ccd9c9461ff47c9802f780f1023b7cb,
title = "Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial",
abstract = "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.",
author = "Jennifer Tom and Min Bao and Larry Tsai and Aditi Qamra and David Summers and Montserrat Carrasco-Triguero and Jacqueline McBride and Rosenberger, {Carrie M} and Lin, {Celia J F} and William Stubbings and Blyth, {Kevin G} and Jordi Carratal{\`a} and Bruno Fran{\c c}ois and Thomas Benfield and Derrick Haslem and Paolo Bonfanti and {van der Leest}, {Cor H} and Nidhi Rohatgi and Lothar Wiese and Luyt, {Charles Edouard} and Farrah Kheradmand and Rosas, {Ivan O} and Fang Cai",
note = "Copyright {\textcopyright} by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.",
year = "2021",
month = oct,
day = "12",
doi = "10.1097/CCM.0000000000005229",
language = "English",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams & Wilkins",

}

RIS

TY - JOUR

T1 - Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial

AU - Tom, Jennifer

AU - Bao, Min

AU - Tsai, Larry

AU - Qamra, Aditi

AU - Summers, David

AU - Carrasco-Triguero, Montserrat

AU - McBride, Jacqueline

AU - Rosenberger, Carrie M

AU - Lin, Celia J F

AU - Stubbings, William

AU - Blyth, Kevin G

AU - Carratalà, Jordi

AU - François, Bruno

AU - Benfield, Thomas

AU - Haslem, Derrick

AU - Bonfanti, Paolo

AU - van der Leest, Cor H

AU - Rohatgi, Nidhi

AU - Wiese, Lothar

AU - Luyt, Charles Edouard

AU - Kheradmand, Farrah

AU - Rosas, Ivan O

AU - Cai, Fang

N1 - Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

PY - 2021/10/12

Y1 - 2021/10/12

N2 - 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.

AB - 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.

U2 - 10.1097/CCM.0000000000005229

DO - 10.1097/CCM.0000000000005229

M3 - Journal article

C2 - 34612846

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

ER -

ID: 68333028