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Clinical Trial
. 2022 Aug 12;17(8):e0271807.
doi: 10.1371/journal.pone.0271807. eCollection 2022.

Timely administration of tocilizumab improves outcome of hospitalized COVID-19 patients

Abraham Rutgers  1 , Peter E Westerweel  2 , Bronno van der Holt  3 , Simone Postma  4 , Marit G A van Vonderen  5 , Djura P Piersma  6 , Douwe Postma  7 , Maarten van den Berge  8 , Eefje Jong  9 , Marten de Vries  10 , Leonie van der Burg  11 , Dennis Huugen  12 , Marjolein van der Poel  13 , Linda M Kampschreur  5 , Marcel Nijland  4 , Jaap H Strijbos  14 , Menno Tamminga  8 , Pim G N J Mutsaers  15 , Suzanne Schol-Gelok  2   16 , Margriet Dijkstra-Tiekstra  4 , Grigory Sidorenkov  17 , Julien Vincenten  18 , Wouter H van Geffen  19 , Marjolein Knoester  20 , Jos Kosterink  21 , Reinold Gans  7 , Coen Stegeman  7 , Gerwin Huls  4 , Tom van Meerten  4
Affiliations
Clinical Trial

Timely administration of tocilizumab improves outcome of hospitalized COVID-19 patients

Abraham Rutgers et al. PLoS One. .

Abstract

Introduction: The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease.

Methods: Open-label randomized phase II clinical trial investigating tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α = 0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days. Secondary objectives included comparing the duration of hospital stay, ICU admittance and duration of ICU stay and the duration of mechanical ventilation.

Results: A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39-0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9-28) in the standard arm versus 9 days (IQR 5-14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p = 0.042).

Conclusions: This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone.

Trial registration: https://www.trialregister.nl/trial/8504.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study flow chart.
Fig 2
Fig 2
A. Mortality by treatment arm. SOC = standard of care, SOC+T = standard of care plus tocilizumab, N = number of patients, d = number of deaths, HR = hazard ratio, CI = confidence interval. B. Mechanical ventilation or death by treatment arm. SOC = standard of care, SOC+T = standard of care plus tocilizumab, N = number of patients, m/d = number of patients with mechanical ventilation or death, HR = hazard ratio, CI = confidence interval.
Fig 3
Fig 3. Forest plot.
R = randomization, SOC = Standard of care, SOC+T = SOC with tocilizumab, ICU = intensive care unit, HR = hazard ratio, CI = confidence interval.
See this image and copyright information in PMC

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