Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: A single-center retrospective study.


Journal

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
ISSN: 1878-3511
Titre abrégé: Int J Infect Dis
Pays: Canada
ID NLM: 9610933

Informations de publication

Date de publication:
Apr 2021
Historique:
received: 04 11 2020
revised: 17 02 2021
accepted: 24 02 2021
pubmed: 2 3 2021
medline: 14 5 2021
entrez: 1 3 2021
Statut: ppublish

Résumé

The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. A retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400-600mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. Totals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17-0.68; P=0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21-0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21-0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49-3.41; P<0.001). The occurrence of secondary infection was similar between both groups. The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19.

Sections du résumé

BACKGROUND BACKGROUND
The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear.
METHODS METHODS
A retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400-600mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied.
RESULTS RESULTS
Totals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17-0.68; P=0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21-0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21-0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49-3.41; P<0.001). The occurrence of secondary infection was similar between both groups.
CONCLUSIONS CONCLUSIONS
The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19.

Identifiants

pubmed: 33647515
pii: S1201-9712(21)00185-5
doi: 10.1016/j.ijid.2021.02.099
pmc: PMC7908857
pii:
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
tocilizumab I031V2H011
Methylprednisolone X4W7ZR7023

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

487-494

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

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Auteurs

Francisco López-Medrano (F)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain. Electronic address: flmedrano@yahoo.es.

María Asunción Pérez-Jacoiste Asín (MA)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Mario Fernández-Ruiz (M)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Octavio Carretero (O)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Antonio Lalueza (A)

Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Guillermo Maestro de la Calle (G)

Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

José Manuel Caro (JM)

Department of Pharmacy, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Cristina de la Calle (C)

Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Mercedes Catalán (M)

Department of Intensive Care Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Rocío García-García (R)

Department of Pneumology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Joaquín Martínez-López (J)

Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain; Department of Hematology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Julia Origüen (J)

Department of Emergency Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Mar Ripoll (M)

Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Rafael San Juan (R)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain.

Hernando Trujillo (H)

Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Ángel Sevillano (Á)

Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Eduardo Gutiérrez (E)

Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Borja de Miguel (B)

Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Fernando Aguilar (F)

Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Carlos Gómez (C)

Department of Oncology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

José Tiago Silva (JT)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Daniel García-Ruiz de Morales (D)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Miguel Saro-Buendía (M)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Ángel Marrero-Sánchez (Á)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Guillermo Chiara-Graciani (G)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Héctor Bueno (H)

Department of Cardiology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Estela Paz-Artal (E)

Department of Immunology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Carlos Lumbreras (C)

Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain; Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

José L Pablos (JL)

Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain; Department of Rheumatology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

José María Aguado (JM)

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain.

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