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. 2021 Apr:105:487-494.
doi: 10.1016/j.ijid.2021.02.099. Epub 2021 Feb 26.

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

Francisco López-Medrano  1 , María Asunción Pérez-Jacoiste Asín  2 , Mario Fernández-Ruiz  2 , Octavio Carretero  2 , Antonio Lalueza  3 , Guillermo Maestro de la Calle  3 , José Manuel Caro  4 , Cristina de la Calle  3 , Mercedes Catalán  5 , Rocío García-García  6 , Joaquín Martínez-López  7 , Julia Origüen  8 , Mar Ripoll  3 , Rafael San Juan  9 , Hernando Trujillo  10 , Ángel Sevillano  10 , Eduardo Gutiérrez  10 , Borja de Miguel  3 , Fernando Aguilar  3 , Carlos Gómez  11 , José Tiago Silva  2 , Daniel García-Ruiz de Morales  2 , Miguel Saro-Buendía  2 , Ángel Marrero-Sánchez  2 , Guillermo Chiara-Graciani  2 , Héctor Bueno  12 , Estela Paz-Artal  13 , Carlos Lumbreras  14 , José L Pablos  15 , José María Aguado  9 ; H12O Immunomodulation Therapy for COVID-19 Group
Affiliations

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

Francisco López-Medrano et al. Int J Infect Dis. 2021 Apr.

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.

Keywords: COVID-19; Corticosteroids; Immunomodulation; Mortality; Outcome; SARS-CoV-2; Therapy; Tocilizumab.

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Figures

Figure 1
Figure 1
Comparison of Kaplan–Meier survival curves in patients included in the CS and CS-TCZ groups: (a) by day +14 (primary study outcome); (b) by day +28 (secondary study outcome). Log-rank P < 0.001 for both comparisons. CS: corticosteroids; TCZ: tocilizumab.
Figure 2
Figure 2
Landmark survival analysis on patients surviving by day +4. Log-rank test P = 0.0024. CS: corticosteroids; TCZ: tocilizumab.
See this image and copyright information in PMC

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