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

Lopez-Medrano, F.; Perez-Jacoiste Asin, M. A.; Fernandez-Ruiz, M.; Carretero, O.; Lalueza, A.; Maestro de la Calle, G.; Caro, J. M.; de la Calle, C.; Catalan, M.; Garcia Garcia, R.; Martinez-Lopez, J.; Origuen, J.; Ripoll, M.; San Juan, R.; Trujillo, H.; Sevillano, A.; Gutierrez, E.; de Miguel, B.; Aguilar, F.; Gomez, C.; Silva, J. T.; Garcia-Ruiz de Morales, D.; Saro-Buendia, M.; Marrero-Sanchez, A.; Chiara-Graciani, G.; Bueno, H.; Paz-Artal, E.; Lumbreras, C.; Pablos, J. L.; Aguado, J. M.

Background: The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID19 associated cytokine release syndrome remains unclear. Methods: We conducted a retrospective single center study including consecutive patients older than 65 years that developed severe COVID19 between March 3 and May 1, 2020 and were treated with corticosteroids at various doses (methylprednisolone [0.5 mg/Kg/12 hours to 250 mg/24 hours]), either alone (CS group) or associated to intravenous tocilizumab (400 to 600 mg, one to three doses) (CS/TCZ group). 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 six point ordinal scale) by day +14. Propensity score (PS)based adjustment and inverse probability of treatment weights (IPTW) were applied. Results: Overall, 181 and 80 patients were included in the CS and CS TCZ groups. 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 to 0.68; P value = 0.002) and IPTW weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21 to 0.68; P value = 0.001). This protective effect was also observed for 28 day mortality (PS adjusted HR: 0.38; 95% CI: 0.21 to 0.72; P value = 0.003). Clinical improvement by day +14 was higher in the CS/TCZ group in the IPTW analysis only (OR: 2.26; 95% CI: 1.49 to 3.41; P value <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 older than 65 years with severe COVID-19.