EClinicalMedicine (Apr 2022)

Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group

  • Olivier Hermine,
  • Xavier Mariette,
  • Raphael Porcher,
  • Felix Djossou,
  • Yann Nguyen,
  • Jean-Benoît Arlet,
  • Laurent Savale,
  • Jean Luc Diehl,
  • Sophie Georgin-Lavialle,
  • Jacques Cadranel,
  • Gilles Pialoux,
  • Karine Lacombe,
  • Arsène Mekinian,
  • Hélène Gros,
  • Xavier Lescure,
  • Jade Ghosn,
  • Elisabeth Coupez,
  • Kevin Grapin,
  • Christophe Rapp,
  • Marc Michel,
  • Anne Lise Lecapitaine,
  • Jean Marie Michot,
  • Nathalie Costedoat-Chalumeau,
  • Liem Binh Luong Nguyen,
  • Luca Semerano,
  • François Raffi,
  • Claire Aguillar,
  • Claire Rouzaud,
  • Jacques Eric Gottenberg,
  • Yves Hansmann,
  • Boris Bienvenu,
  • Jonathan London,
  • Franklin Samou Fantchou,
  • Felix Ackermann,
  • Antoine Gros,
  • Alexandre Morel,
  • Nicolas Gambier,
  • Damien Sène,
  • Bruno Mégarbane,
  • Elie Azoulay,
  • Serge Bureau,
  • Maxime Dougados,
  • Joseph Emmerich,
  • Muriel Fartoukh,
  • Bertrand Guidet,
  • Marc Humbert,
  • Mathieu Mahevas,
  • Frédéric Pène,
  • Frédéric Schlemmer,
  • Valérie Pourcher-Martinez,
  • Annick Tibi,
  • Gabriel Baron,
  • Elodie Perrodeau,
  • Stéphanie Baron,
  • Gabriel Steg,
  • Yazdan Yazdapanah,
  • Tabassome Simon,
  • Matthieu Resche-Rigon,
  • Pierre-Louis Tharaux,
  • Philippe Ravaud

Journal volume & issue
Vol. 46
p. 101362

Abstract

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Summary: Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42–1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19–20–0151, PHRC COVID-19–20–0029], Fondation de l'Assistance Publique – Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale” (FRM). Tocilizumab was provided by Roche.

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