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Rigshospitalet - en del af Københavns Universitetshospital
E-pub ahead of print

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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  • Jennifer Tom
  • Min Bao
  • Larry Tsai
  • Aditi Qamra
  • David Summers
  • Montserrat Carrasco-Triguero
  • Jacqueline McBride
  • Carrie M Rosenberger
  • Celia J F Lin
  • William Stubbings
  • Kevin G Blyth
  • Jordi Carratalà
  • Bruno François
  • Thomas Benfield
  • Derrick Haslem
  • Paolo Bonfanti
  • Cor H van der Leest
  • Nidhi Rohatgi
  • Lothar Wiese
  • Charles Edouard Luyt
  • Farrah Kheradmand
  • Ivan O Rosas
  • Fang Cai
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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.

TidsskriftCritical Care Medicine
StatusE-pub ahead of print - 12 okt. 2021

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