Tocilizumab and steroid treatment in patients with COVID-19 pneumonia

被引:73
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
来源
PLOS ONE | 2020年 / 15卷 / 08期
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.
引用
收藏
页数:16
相关论文
共 27 条
  • [21] Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China
    Wu, Chaomin
    Chen, Xiaoyan
    Cai, Yanping
    Xia, Jia'an
    Zhou, Xing
    Xu, Sha
    Huang, Hanping
    Zhang, Li
    Zhou, Xia
    Du, Chunling
    Zhang, Yuye
    Song, Juan
    Wang, Sijiao
    Chao, Yencheng
    Yang, Zeyong
    Xu, Jie
    Zhou, Xin
    Chen, Dechang
    Xiong, Weining
    Xu, Lei
    Zhou, Feng
    Jiang, Jinjun
    Bai, Chunxue
    Zheng, Junhua
    Song, Yuanlin
    [J]. JAMA INTERNAL MEDICINE, 2020, 180 (07) : 934 - 943
  • [22] Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention
    Wu, Zunyou
    McGoogan, Jennifer M.
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2020, 323 (13): : 1239 - 1242
  • [23] Effective treatment of severe COVID-19 patients with tocilizumab
    Xu, Xiaoling
    Han, Mingfeng
    Li, Tiantian
    Sun, Wei
    Wang, Dongsheng
    Fu, Binqing
    Zhou, Yonggang
    Zheng, Xiaohu
    Yang, Yun
    Li, Xiuyong
    Zhang, Xiaohua
    Pan, Aijun
    Wei, Haiming
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (20) : 10970 - 10975
  • [24] Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study
    Yang, Xiaobo
    Yu, Yuan
    Xu, Jiqian
    Shu, Huaqing
    Xia, Jia'an
    Liu, Hong
    Wu, Yongran
    Zhang, Lu
    Yu, Zhui
    Fang, Minghao
    Yu, Ting
    Wang, Yaxin
    Pan, Shangwen
    Zou, Xiaojing
    Yuan, Shiying
    Shang, You
    [J]. LANCET RESPIRATORY MEDICINE, 2020, 8 (05) : 475 - 481
  • [25] Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality
    Zhang, Chi
    Wu, Zhao
    Li, Jia-Wen
    Zhao, Hong
    Wang, Gui-Qiang
    [J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2020, 55 (05)
  • [26] The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China
    Zhang, Wen
    Zhao, Yan
    Zhang, Fengchun
    Wang, Qian
    Li, Taisheng
    Liu, Zhengyin
    Wang, Jinglan
    Qin, Yan
    Zhang, Xuan
    Yan, Xiaowei
    Zeng, Xiaofeng
    Zhang, Shuyang
    [J]. CLINICAL IMMUNOLOGY, 2020, 214
  • [27] Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
    Zhou, Fei
    Yu, Ting
    Du, Ronghui
    Fan, Guohui
    Liu, Ying
    Liu, Zhibo
    Xiang, Jie
    Wang, Yeming
    Song, Bin
    Gu, Xiaoying
    Guan, Lulu
    Wei, Yuan
    Li, Hui
    Wu, Xudong
    Xu, Jiuyang
    Tu, Shengjin
    Zhang, Yi
    Chen, Hua
    Cao, Bin
    [J]. LANCET, 2020, 395 (10229) : 1054 - 1062