Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection: A Spanish, Multicenter, Cohort Study

Belén Ruiz-Antorán, Aránzazu Sancho-López, Ferrán Torres, Víctor Moreno-Torres, Itziar de Pablo-López, Paulina García-López, Francisco Abad-Santos, Clara M. Rosso-Fernández, Ana Aldea-Perona, Eva Montané, Ruth M. Aparicio-Hernández, Roser Llop-Rius, Consuelo Pedrós, Paloma Gijón, Carolina Hernández-Carballo, María J. Pedrosa-Martínez, Consuelo Rodríguez-Jiménez, Guillermo Prada-Ramallal, Lourdes Cabrera-García, Josefa A. Aguilar-GarcíaRocío Sanjuan-Jimenez, Evelyn I. Ortiz-Barraza, Enrique Sánchez-Chica, Ana Fernández-Cruz, X. Fernández Sala, P. Díaz Pellicer, S. Grau Cerrato, José Manuel Dodero Anillo, Alberto Romero Palacios, Elisa Cubiles, Mª Ángeles Lobo Acosta, Reyes Fresneda Gutierrez, Alicia Marían Candón, Sonsoles Salto Alejandre, Jose Miguel Cisneros Herreros, Elisa Cordero Matía, Carmen Infante Dominguez, Juan Carlos Crespo Rivas, Macarena López Verdugo, Isabel Suarez Toste, Paloma Díaz Pérez, Francesca Mitjavila Villero, Guillermo Suárez Cuartin, Carlota Gudiol Gonzalez, Adriana Iriarte Fuster, Mercè Gasa Galmes, Sandra Pérez, Dolores Rodríguez Cumplido, Arístides de León Gil, Emilio J. Sanz, Francisco Sanz-Herrero, Francesc Puchades, Pilar Ortega-García, José Antonio Díaz-Peromingo, Carlos Rodríguez-Moreno, Daniel Lozano, Ana Terleira, María Estela González Castro, Sergio Ferra Murcia, Elena María Gázquez Aguilera, Elena Pintos-Sanchez, Pablo Zubiaur, Elena Santos-Molina, Marcos Navares-Gómez, Gina Mejia Abril, Amelia García-Luque, Miguel Puerro-Vicente, María Jesús Sánchez Carrillo, M. Ángeles Gálvez Múgica, Mónica Aguilar Jiménez, Cristina Sánchez Díaz, Cristina Avendaño Solá, Patricia Mills-Sánchez, Manuel Valle, Gustavo Centeno, Concepción Payares, Antonio F.Caballero Bermejo, Elena Diago, Rosa Malo de Molina, Juan Antonio Vargas Nuñez, Elena Muñez, Antonio Ramos, Ana María Barriocanal, Ana Pilar Pérez-Acevedoc, Melani Núñez-Montero, María Olmedo, Sofia De la Villa, Enrique Nuño Álvarez, M. I. Lucena, Josefa Andrea Aguilar García, José Javier García Alegría

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Abstract

Background: We aimed to determine the impact of tocilizumab use on severe COVID-19 (coronavirus disease 19) pneumonia mortality. Methods: We performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by inverse probability of the treatment weights (IPTW). Tocilizumab's effect in patients receiving steroids during the 48 h following inclusion was analysed. Results: During the study period, 506 patients with severe COVID-19 fulfilled the inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days [interquartile range (IQR) 8–14]. Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls: 16.8% versus 31.5%, hazard ratio (HR) 0.514 [95% confidence interval (95% CI) 0.355–0.744], p <0.001; weighted HR 0.741 (95% CI 0.619–0.887), p = 0.001. Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment [relative risk reduction (RRR) 46.7%]. We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in those treated with tocilizumab than in those treated with steroids alone [10.9% versus 40.2%, HR 0.511 (95% CI 0.352–0.741), p = 0.036; weighted HR 0.6 (95% CI 0.449–0.804), p <0.001] (interaction p = 0.094). Conclusions: These results show that survival of patients with severe COVID-19 is higher in those treated with tocilizumab than in those not treated and that tocilizumab's effect adds to that of steroids administered to non-intubated patients with COVID-19 during the first 48 h of presenting with respiratory failure despite oxygen therapy. Randomised controlled studies are needed to confirm these results. Trial registration: European Union electronic Register of Post-Authorization Studies (EU PAS Register) identifier, EUPAS34415
Original languageEnglish
JournalInfectious Diseases and Therapy
DOIs
Publication statusPublished - 2020

Keywords

  • COVID-19
  • Mortality
  • SARS-CoV-2
  • Steroids
  • Tocilizumab

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