Tocilizumab and steroid treatment in patients with COVID-19 pneumonia

被引:76
作者
Mikulska, Malgorzata [1 ,2 ]
Nicolini, Laura Ambra [2 ]
Signori, Alessio [3 ]
Di Biagio, Antonio [1 ,2 ]
Sepulcri, Chiara [1 ]
Russo, Chiara [1 ]
Dettori, Silvia [1 ]
Berruti, Marco [1 ]
Sormani, Maria Pia [3 ]
Giacobbe, Daniele Roberto [1 ,2 ]
Vena, Antonio [2 ]
De Maria, Andrea [1 ,2 ]
Dentone, Chiara [2 ]
Taramasso, Lucia [2 ]
Mirabella, Michele [1 ,2 ]
Magnasco, Laura [1 ,2 ]
Mora, Sara [4 ]
Delfino, Emanuele [2 ]
Toscanini, Federica [2 ]
Balletto, Elisa [1 ,2 ]
Alessandrini, Anna Ida [2 ]
Baldi, Federico [1 ]
Briano, Federica [1 ]
Camera, Marco [2 ]
Dodi, Ferdinando [2 ]
Ferrazin, Antonio [2 ]
Labate, Laura [1 ]
Mazzarello, Giovanni [2 ]
Pincino, Rachele [1 ]
Portunato, Federica [2 ,5 ]
Tutino, Stefania [1 ]
Barisione, Emanuela [6 ]
Bruzzone, Bianca [7 ]
Orsi, Andrea [7 ,8 ]
Schenone, Eva [2 ]
Rosseti, Nirmala [2 ]
Sasso, Elisabetta [9 ]
Da Rin, Giorgio [10 ]
Pelosi, Paolo [11 ,12 ]
Beltramini, Sabrina [9 ]
Giacomini, Mauro [4 ]
Icardi, Giancarlo [7 ,8 ]
Gratarola, Angelo [13 ]
Bassetti, Matteo [1 ,2 ]
机构
[1] Univ Genoa, Dept Hlth Sci DISSAL, Div Infect Dis, Genoa, Italy
[2] IRCCS Osped Policlin San Martino, Div Infect Dis, Genoa, Italy
[3] Univ Genoa, Dept Hlth Sci, Sect Biostat, Genoa, Italy
[4] Univ Genoa, Dept Informat Bioengn Robot & Syst Engn, Genoa, Italy
[5] Univ Campania Luigi Vanvitelli, Infect Dis Unit, Naples, Italy
[6] IRCCS Osped Policlin San Martino, Intervent Pulmonol Unit, Genoa, Italy
[7] IRCCS Osped Policlin San Martino, Hyg Unit, Genoa, Italy
[8] Univ Genoa, Dept Hlth Sci, Genoa, Italy
[9] IRCCS Osped Policlin San Martino, Pharm Complex Unit, Genoa, Italy
[10] IRCCS Osped Policlin San Martino, Med Lab, Genoa, Italy
[11] Univ Genoa, Dept Surg Sci & Integrated Diagnost, Genoa, Italy
[12] San Martino Policlin Hosp, IRCCS Oncol & Neurosci, Anesthesia & Intens Care, Genoa, Italy
[13] San Martino Policlin Hosp, Dept Emergency & Urgency, IRCCS Oncol & Neurosci, Genoa, Italy
关键词
CLINICAL CHARACTERISTICS;
D O I
10.1371/journal.pone.0237831
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 24(th), 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/FiO(2)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), HR(OW)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), HR(OW)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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