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

López-Medrano, Francisco; Pérez-Jacoiste Asín, María Asunción; Fernández-Ruiz, Mario; Carretero, Octavio; Lalueza, Antonio; Maestro de la Calle, Guillermo; Caro, José Manuel; de la Calle, Cristina; Catalán, Mercedes; García-García, Rocío; Martínez-López, Joaquín; Origüen, Julia; Ripoll, Mar; San Juan, Rafael; Trujillo, Hernando; Sevillano, Ángel; Gutiérrez, Eduardo; de Miguel, Borja; Aguilar, Fernando; Gómez, Carlos; Silva, José Tiago; García-Ruiz de Morales, Daniel; Saro-Buendía, Miguel; Marrero-Sánchez, Ángel; Chiara-Graciani, Guillermo; Bueno, Héctor; Paz-Artal, Estela; Lumbreras, Carlos; Pablos, José L.; Aguado, José María

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 We conducted a retrospective single-center study including consecutive patients ≥65 years that developed severe COVID-19 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 (400-600 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 – 0.68; P-value = 0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21 – 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 – 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 – 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 ≥65 years with severe COVID-19.