Compassionate Use of Tocilizumab in Severe SARS-CoV2 Pneumonia. When late administration is too late

Gorgolas, Miguel; Cabello, Alfonso; Perez, Laura Prieto; Alvarez, Felipe Villar; Alvarez, Beatriz Alvarez; Nieto, Maria Jesus Rodriguez; Acosta, Irene Carrillo; Ormaechea, Itziar Fernandez; Al-Hayani, Aws; Carballosa, Pilar; Martinez, Silvia Calpena; Blas, Farah Ezzine de; Gonzalez, Marina Castellanos; Prieto, Alba Naya; Heras, Marta Lopez de las; Guzman, Marcel Jose Rodriguez; Guijarro, Ana Cordero; Lavado, Antonio Broncano; Valcayo, Alicia Macias; Garcia, Marta Martin; Martinez, Javier Becares; Roblas, Ricardo Fernandez; Pinilla, Miguel A Piris; Alen, Jose Fortes; Pernaute, Olga Sanchez; Bueno, Fredeswinda Romero; Frades, Sarah Heili; Romero, German Peces Barba

Introduction Tocilizumab is an interleukin 6 receptor antagonist which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), aiming to ameliorate the cytokine release syndrome (CRS) -induced acute respiratory distress syndrome (ARDS). However, there is no data about the best moment for its administration along the course of the disease. Methods We provided tocilizumab on a compassionate-use basis to patients with SSP hospitalized (excluding intensive care and intubated cases) who required oxygen support to have a saturation >93%. Primary endpoint was intubation or death after 24 hours of its administration. Patients received at least one dose of 400 mg intravenous tocilizumab during March 8-2020, through April 20-2020. Findings A total of 207 patients were studied and 186 analysed. The mean age was 65 years and 68% were male. A co-existing condition was present in 68 % of cases. At baseline, 114 (61%) required oxygen support with FiO2 >0.5 % and 72 (39%) <0.5%. Early administration of tocilizumab, when the need of oxygen support was still below FiO2 <0.5%, was significantly more effective than given it in advanced stages (FiO2 >0.5 %), achieving lower rates of intubation or death (13% vs 37% repectively, p<0.001). Interpretation The benefit of tocilizumab in severe SARS-Cov-2 pneumonia is only expected when it is administrated before the need of high oxygen support.