Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)
Authors: Jesús Rodríguez-Baño, Jerónimo Pachón, Jordi Carratalà, Pablo Ryan, Inmaculada Jarrín, María Yllescas, José Ramón Arribas, Juan Berenguer, Esther Aznar Muñoz, Pedro Gil Divasson, Patricia González Muñiz, Clara Muñoz Aguirre, Marta Díaz Menéndez, Fernando de la Calle Prieto, Marta Arsuaga Vicente, Elena Trigo Esteban, Ignacio Pérez Valero, Rosa de Miguel Buckley, Julen Cadiñaños Loidi, Beatriz Diaz Pollan, Luz Martín Carbonero, Juan Carlos Ramos Ramos, Belén Loeches Yagüe, Rocío Montejano Sánchez, Juan González García, Julio García Rodríguez, Juan Berenguer, Margarita Ramírez, Isabel Gutiérrez, Francisco Tejerina, Teresa Aldámiz-Echevarría, Cristina Díez, Chiara Fanciulli, Leire Pérez-Latorre, Blanca Pinilla, Juan Carlos López, Ana Such Diaz, Elena Álvaro Alonso, Juan Torres Macho, Guillermo Cuevas Tascon, Eva Jiménez González de Buitrago, Fátima Brañas Baztán, Jorge Valencia de la Rosa, Mario Pérez Butragueño, Inés Fernández Jiménez, Gemma Muñiz Nicolás, Antonia Sepúlveda Berrocal, Alberto Gato Díez, María Pilar Toledano Sierra, María Paz García Butenegro, Ana Isabel Peláez Ballesta, Elena Morcillo Rodríguez, Isidoro Fernández Romero, Cristina Peláez Ballesta, María Isabel Guirado Torrecillas, Josune Goikoetxea Agirre, Elena Bereciartua Bastarrica, Laura Guio Carrión, Regino Rodríguez Álvarez, Marta Ibarrola Hierro, Isabel A. Pérez Hernández, Inés Pérez Zapata, Sergio Román Soto, Mohamed Kallouchi, Juan Ramón Domínguez Vicent, Rafae Silvariño Fernández, Jon Ugalde Espiñeira, Ainhoa Sanjuan López, Silvia García Martínez, Mikel Temprano Gogenola, Víctor Asensi, Silvia Suárez, Lucia Suárez, Carmen Yllera, María Rivas-Carmenado, Alberto Romero-Palacios, Jesús Ruiz Aragón, Patricia Jiménez Aguilar, Ma Luisa Fernández Ávila, Rosario Castilla Ortiz, Vanesa Alende Castro, Cristina Pérez García, Marta Fernández Morales, María Lorena María Valle Feijoo Begoña Rodríguez Ferreira, Joan Gómez-Junyent, Judit Villar-García, Inmaculada López-Montesinos, Itziar Arrieta-Aldea, Abora Rial-Villavecchia, Elisa García Vázquez, Aychel Elena Roura Piloto, Encarnación Moral Escudero, Alicia Hernández Torres, Helena Albendín Iglesias, David Vinuesa García, Clara Martínez Montes, Francisco Javier De la Hera Fernández, Francisco Anguita Santos, Andrés Ruiz Sancho, Vicens Díaz de Brito Fernández, Montserrat Sanmarti Vilamala, Sergio España Cueto, Daniel Molina Morant, Araceli González-Cuevas, Joel Elías Chara Cervantes, Guillem Policarpo Torres, Meritxell Ortega Montoliu, Mònica Angerri Nadal, Ariadna De Genover Gil, Eleni Patera, Rita Godoy Lorenzo, Evangelia Anna María Zioga, Virginia Isern Fernández, Carlos Enrique Sabbagh Fajardo, Ana Ferrer Ribera, Carlos Bea Serrano, Rosa Oltra Sempere, Sara Vela Bernal, Paloma Albiol Viñals, Miguel Pedromingo Kus, María Ángeles Garcinuño, Silvana Fiorante, Sergio Pérez Pinto, Alexandra de la Vega, María Carmen Fariñas Álvarez, Claudia González Rico, Francisco Arnaiz de las Revillas, Teresa Giménez, Jorge Calvo, Yolanda Meije Castillo, Alejandra Duarte Borges, Júlia Pareja Coca, Mercedes Clemente Presas, Xavier Sanz Salvador, Ma Teresa Pérez Rodríguez, Adrián Sousa, Alexandre Pérez González, Rebeca Longueira, Alejandro Araujo, Blanca Alonso Martínez, Laura García Escudero, Sara Lidia Kamel Rey, David Roa Alonso, Juan Pablo Avilés Parra, Iván Pelegrín Senent, Rosana Rouco Esteves Marques, Laia Raich Montiu, Jessica Souto Higueras, Manuel Alejandro Gálvez Bobadilla, Jorge Parra Ruiz, Violeta Ramos Sesma, Sara Velasco Fuentes, Laura García Pereña, Alfonso Lluna Carrascosa, Sergio Gilaberte Reyzábal, Mónica Liébana Gómez, Juan Salillas Hernando, Alberto Serrano Martínez, Miguel Torralba González de Suso, Patricia Martínez Martín, Isabel Rábago Lorite, Patricia González-Ruano Pérez, Beatriz Pérez-Monte Mínguez, Ángeles García Flores, Pere Comas Casanova, Andrea Martín Plata, Sergio Manuel Santana Báez, Oscar Sanz Peláez, Karim Mohamed Ramírez, José María Robaina Bordón, Helem Haydeé Vílchez Rueda, Melchor Riera Jaume, Gemma Mut Ramon, Meritxell Gavalda Manso, Lluis Planas Bibiloni, Laura Castelo Corral, Lucía Ramos Merino, Efrén Sánchez Vidal, María Rodríguez Mayo, Enrique Míguez Rey, José M. García de Lomas Guerrero, Javier De la Torre Lima, Ana Correa Ruiz, Fernando Fernández Sánchez, Nicolás Jiménez-García, José Luis Sierra-Monzón, Borja Gracia-Tello, María Hernández-Bonaga, Galadriel Pellejero, Marta Asín-Corrochano, Lucia Boix Palop, Esther Calbo, Cristina Badía, Beatriz Dietl, Gómez Lucía, Ángel Domínguez-Castellano, María José Ríos-Villegas, María D. del Toro, Zaira R. Palacios Baena, Elena Salamanca-Rivera, Elena Marín, Virginia Almadana, Salvador Pérez-Galera, Luisa González-Iglesias, Gabriela Abelenda-Alonso, Claudia Álvarez-Pouso, Francesc Escrihuela, Carlota Gudiol, Laia Lorenzo-Esteller, Jordi Niubó, Daniel Podzamczer, Miquel Pujol, Alexander Rombauts, Miguel Salvert Lletí, Ricardo Gil Sánchez, Marta Jiménez Escrig, Laura Parra Gómez, Mariona Tasias Pitarch, Marta Navarro Vilasaró, María Luisa Machado Sicilia, Aina Gomila Grange, Sonia Calzado Isbert, Nerea Carrasco Antón, Elizabet Petkova-Saiz, Alfonso Cabello Úbeda, Miguel Górgolas Hernández-Mora, Olga Sánchez-Pernaute, Carlos Dueñas Gutiérrez, Javier Martin Guerra, José Javier Castrodeza Sanz, Virginia Fernández Espinilla, Laura Rodríguez Fernández, Juan González-Moreno, Aroa Villoslada Gelabert, María Antonia Ribot Sanso, María Victoria Fernández-Baca, Almudena Hernández Milian, Miguel Ángel Morán Rodríguez, Zuriñe Ortiz de Zárate Ibarra, José Joaquin Portu Zapirain, Ester Saez de Adana Arroniz, Juan Carlos Gainzarain Arana, Olga Meca Birlanga, Ma Jesús del Amor Espín, Montserrat Viqueira González, Josefina García García, Onofre Martínez Madrid, Enrique Bernal Morell, Antonia Alcaraz, Ángeles Muñoz, Ignacio Pina, Vicente de la Rosa, Tamara Caínzos Romero, Sabela Sánchez Trigo, Ana Isabel Mariño Callejo, Hortensia Álvarez Díaz, Nieves Valcarce Pardeiro, Adriana Sánchez Serrano, Diana Piñar Cabezos, Eva Pilar García Villalba, Carmen Aguayo Jiménez, María Ruíz Campuzano, Virginia Naranjo Velasco, Marta Santos Peña, Juan Mora Delgado, Israel Sevilla Moreno, Cristina Lojo Cruz, Xabier Kortajarena Urkola, José Antonio Iribarren Loyarte, María Jesús Bustinduy Odriozola, Maialen Ibarguren Pinilla, Ignacio Álvarez Rodríguez, Francisco Javier Martínez Marcos, Francisco Javier Rodríguez Gómez, Isabel Asschert Agüero, Francisco Muñoz Beamud, Antonio José Ruiz Reina, Jara Llenas-García, Inmaculada González-Cuello, Elena Hellín-Valiente, Esther Martínez Birlanga, José Manuel Tafalla Torres, Jorge Calderón Parra, Gabriela Escudero López, Isabel Gutiérrez Martín, Ane Andrés Eisenhofer, Sonia García Prieto, Raquel Álvarez Franco, Daniel Roger Zapata, Blanca Martínez Cifre, Elena Aranda Rife, Irene Martín Rubio, André Barbosa Ventura, Javier Garrido, Concepción Gonzalo, Iván Piñero, Nieves de la Cruz Felipe, Eva Talavera García, Marta Lamata Subero, Paula Mendoza Roy, María Soledad García de Carlos, Justo Lajusticia Aisa, Lorea Arteche Eguizabal, Ainhoa Urrutia Losada, Saioa Domingo Echaburu, Pedro Ángel Cuadros Tito, Gurutz Orbe Narváez, Ma del Carmen Liébana Martos, Carolina Roldán Fontana, Carmen Herrero Rodríguez, Gaspar Duro Ruiz, Santiago Pérez Parra, Arantzazu Mera Fidalgo, Miquel Hortos Alsina, Ana Alberich Conesa, Lourdes Bladé Vidal, Nicolás Merchante Gutiérrez, Eva León Jiménez, Reinaldo Espíndola Gómez, María Erostarbe Gallardo, Pedro Martínez Pérez-Crespo, José Miguel Cisneros, Manuela Aguilar-Guisado, Teresa Aldabó, Claudio Bueno, Elisa Cordero-Matía, Ana Escoresca, Carmen Infante, Martín Guillermo, Sonsoles Salto, Francesca Gioia, Pilar Vizcarra, Jesús Fortún Abete, Pilar Martín Dávila, Santiago Moreno Guillén, José A. Oteo Revuelta, Concepción García-García, Paula Santibañez Sáenz, Cristina Cervera Acedo, José M. Azcona Gutiérrez, José María Reguera Iglesias, Antonio Plata Ciezar, Lucia Valiente de Santis, Beatriz Sobrino Diaz, Juan Diego Ruiz Mesa
Journal: Clinical Microbiology and Infection (2020)

ObjectivesThe objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters.MethodsA cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs).ResultsIn all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001).ConclusionsTocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation.