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Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: A single-center retrospective study.
Int J Infect Dis. 2021 Apr; 105:487-494.IJ

Abstract

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

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

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

The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19.

Authors+Show Affiliations

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.Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.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 Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Pharmacy, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Intensive Care Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Pneumology, 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; Department of Hematology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Emergency Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.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.Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Oncology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.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 Cardiology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.Department of Immunology, 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; 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; Department of Rheumatology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.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.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33647515

Citation

López-Medrano, Francisco, et al. "Combination Therapy With Tocilizumab and Corticosteroids for Aged Patients With Severe COVID-19 Pneumonia: a Single-center Retrospective Study." International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases, vol. 105, 2021, pp. 487-494.
López-Medrano F, Pérez-Jacoiste Asín MA, Fernández-Ruiz M, et al. Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: A single-center retrospective study. Int J Infect Dis. 2021;105:487-494.
López-Medrano, F., Pérez-Jacoiste Asín, M. A., Fernández-Ruiz, M., Carretero, O., Lalueza, A., Maestro de la Calle, G., Caro, J. M., de la Calle, C., Catalán, M., García-García, R., Martínez-López, J., Origüen, J., Ripoll, M., San Juan, R., Trujillo, H., Sevillano, Á., Gutiérrez, E., de Miguel, B., Aguilar, F., ... Aguado, J. M. (2021). Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: A single-center retrospective study. International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases, 105, 487-494. https://doi.org/10.1016/j.ijid.2021.02.099
López-Medrano F, et al. Combination Therapy With Tocilizumab and Corticosteroids for Aged Patients With Severe COVID-19 Pneumonia: a Single-center Retrospective Study. Int J Infect Dis. 2021;105:487-494. PubMed PMID: 33647515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: A single-center retrospective study. AU - López-Medrano,Francisco, AU - Pérez-Jacoiste Asín,María Asunción, AU - Fernández-Ruiz,Mario, AU - Carretero,Octavio, AU - Lalueza,Antonio, AU - Maestro de la Calle,Guillermo, AU - Caro,José Manuel, AU - de la Calle,Cristina, AU - Catalán,Mercedes, AU - García-García,Rocío, AU - Martínez-López,Joaquín, AU - Origüen,Julia, AU - Ripoll,Mar, AU - San Juan,Rafael, AU - Trujillo,Hernando, AU - Sevillano,Ángel, AU - Gutiérrez,Eduardo, AU - de Miguel,Borja, AU - Aguilar,Fernando, AU - Gómez,Carlos, AU - Silva,José Tiago, AU - García-Ruiz de Morales,Daniel, AU - Saro-Buendía,Miguel, AU - Marrero-Sánchez,Ángel, AU - Chiara-Graciani,Guillermo, AU - Bueno,Héctor, AU - Paz-Artal,Estela, AU - Lumbreras,Carlos, AU - Pablos,José L, AU - Aguado,José María, AU - ,, Y1 - 2021/02/26/ PY - 2020/11/04/received PY - 2021/02/17/revised PY - 2021/02/24/accepted PY - 2021/3/2/pubmed PY - 2021/5/14/medline PY - 2021/3/1/entrez KW - COVID-19 KW - Corticosteroids KW - Immunomodulation KW - Mortality KW - Outcome KW - SARS-CoV-2 KW - Therapy KW - Tocilizumab SP - 487 EP - 494 JF - International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases JO - Int J Infect Dis VL - 105 N2 - 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: 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: 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: The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19. SN - 1878-3511 UR - https://www.unboundmedicine.com/medline/citation/33647515/Combination_therapy_with_tocilizumab_and_corticosteroids_for_aged_patients_with_severe_COVID_19_pneumonia:_A_single_center_retrospective_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1201-9712(21)00185-5 DB - PRIME DP - Unbound Medicine ER -