Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial.
Crit Care Med
; 50(3): 398-409, 2022 03 01.
Article
in English
| MEDLINE | ID: covidwho-1455371
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 21 to IV tocilizumab 8 mg/kg or placebo. MEASUREMENTS AND MAINRESULTS:
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibodies, Monoclonal, Humanized
/
COVID-19
/
COVID-19 Drug Treatment
Type of study:
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Limits:
Female
/
Humans
/
Male
Language:
English
Journal:
Crit Care Med
Year:
2022
Document Type:
Article
Affiliation country:
CCM.0000000000005229
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