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Observational Study
. 2020 Aug 20;15(8):e0237831.
doi: 10.1371/journal.pone.0237831. eCollection 2020.

Tocilizumab and steroid treatment in patients with COVID-19 pneumonia

Malgorzata Mikulska  1   2 , Laura Ambra Nicolini  2 , Alessio Signori  3 , Antonio Di Biagio  1   2 , Chiara Sepulcri  1 , Chiara Russo  1 , Silvia Dettori  1 , Marco Berruti  1 , Maria Pia Sormani  3 , Daniele Roberto Giacobbe  1   2 , Antonio Vena  2 , Andrea De Maria  1   2 , Chiara Dentone  2 , Lucia Taramasso  2 , Michele Mirabella  1   2 , Laura Magnasco  1   2 , Sara Mora  4 , Emanuele Delfino  2 , Federica Toscanini  2 , Elisa Balletto  1   2 , Anna Ida Alessandrini  2 , Federico Baldi  1 , Federica Briano  1 , Marco Camera  2 , Ferdinando Dodi  2 , Antonio Ferrazin  2 , Laura Labate  1 , Giovanni Mazzarello  2 , Rachele Pincino  1 , Federica Portunato  2   5 , Stefania Tutino  1 , Emanuela Barisione  6 , Bianca Bruzzone  7 , Andrea Orsi  7   8 , Eva Schenone  2 , Nirmala Rosseti  2 , Elisabetta Sasso  9 , Giorgio Da Rin  10 , Paolo Pelosi  11   12 , Sabrina Beltramini  9 , Mauro Giacomini  4 , Giancarlo Icardi  7   8 , Angelo Gratarola  13 , Matteo Bassetti  1   2
Affiliations
Observational Study

Tocilizumab and steroid treatment in patients with COVID-19 pneumonia

Malgorzata Mikulska et al. PLoS One. .

Abstract

Introduction: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome.

Methods: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW).

Results: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p = 0.025.

Conclusion: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.

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Conflict of interest statement

The authors have declared that no competing interests exist

Figures

Fig 1
Fig 1. The flowchart of the included patients.
Fig 2
Fig 2. Adjusted failure-free (intubation or death) survival in patients who received tocilizumab and/or methylprednisolone and Standard Of Care (SOC) vs. SOC.
Fig 3
Fig 3. Adjusted failure-free survival in patients receiving anti-inflammatory treatment: Tocilizumab only, methylprednisolone only, and combined treatment.
Fig 4
Fig 4. Adjusted overall survival in patients who received tocilizumab and/or methylprednisolone and Standard Of Care (SOC) vs. SOC.
See this image and copyright information in PMC

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