TY - JOUR
T1 - Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome
T2 - A retrospective case-control survival analysis of 128 patients
AU - Humanitas and Gavazzeni / Castelli COVID-19 Task Forces
AU - Canziani, Lorenzo M
AU - Trovati, Serena
AU - Brunetta, Enrico
AU - Testa, Amidio
AU - De Santis, Maria
AU - Bombardieri, Emilio
AU - Guidelli, Giacomo
AU - Albano, Giovanni
AU - Folci, Marco
AU - Squadroni, Michela
AU - Beretta, Giordano D
AU - Ciccarelli, Michele
AU - Castoldi, Massimo
AU - Lleo, Ana
AU - Aghemo, Alessio
AU - Vernile, Laura
AU - Malesci, Alberto
AU - Omodei, Paolo
AU - Angelini, Claudio
AU - Badalamenti, Salvatore
AU - Cecconi, Maurizio
AU - Cremonesi, Alberto
AU - Selmi, Carlo
N1 - Copyright © 2020 Elsevier Ltd. All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - In cases of COVID-19 acute respiratory distress syndrome, an excessive host inflammatory response has been reported, with elevated serum interleukin-6 levels. In this multicenter retrospective cohort study we included adult patients with COVID-19, need of respiratory support, and elevated C-reactive protein who received intravenous tocilizumab in addition to standard of care. Control patients not receiving tocilizumab were matched for sex, age and respiratory support. We selected survival as the primary endpoint, along with need for invasive ventilation, thrombosis, hemorrhage, and infections as secondary endpoints at 30 days. We included 64 patients with COVID-19 in the tocilizumab group and 64 matched controls. At baseline the tocilizumab group had longer symptom duration (13 ± 5 vs. 9 ± 5 days) and received hydroxychloroquine more often than controls (100% vs. 81%). The mortality rate was similar between groups (27% with tocilizumab vs. 38%) and at multivariable analysis risk of death was not significantly influenced by tocilizumab (hazard ratio 0.61, 95% confidence interval 0.33-1.15), while being associated with the use at baseline of non invasive mechanical or invasive ventilation, and the presence of comorbidities. Among secondary outcomes, tocilizumab was associated with a lower probability of requiring invasive ventilation (hazard ratio 0.36, 95% confidence interval 0.16-0.83; P = 0.017) but not with the risk of thrombosis, bleeding, or infections. The use of intravenous tocilizumab was not associated with changes in 30-day mortality in patients with COVID-19 severe respiratory impairment. Among the secondary outcomes there was less use of invasive ventilation in the tocilizumab group.
AB - In cases of COVID-19 acute respiratory distress syndrome, an excessive host inflammatory response has been reported, with elevated serum interleukin-6 levels. In this multicenter retrospective cohort study we included adult patients with COVID-19, need of respiratory support, and elevated C-reactive protein who received intravenous tocilizumab in addition to standard of care. Control patients not receiving tocilizumab were matched for sex, age and respiratory support. We selected survival as the primary endpoint, along with need for invasive ventilation, thrombosis, hemorrhage, and infections as secondary endpoints at 30 days. We included 64 patients with COVID-19 in the tocilizumab group and 64 matched controls. At baseline the tocilizumab group had longer symptom duration (13 ± 5 vs. 9 ± 5 days) and received hydroxychloroquine more often than controls (100% vs. 81%). The mortality rate was similar between groups (27% with tocilizumab vs. 38%) and at multivariable analysis risk of death was not significantly influenced by tocilizumab (hazard ratio 0.61, 95% confidence interval 0.33-1.15), while being associated with the use at baseline of non invasive mechanical or invasive ventilation, and the presence of comorbidities. Among secondary outcomes, tocilizumab was associated with a lower probability of requiring invasive ventilation (hazard ratio 0.36, 95% confidence interval 0.16-0.83; P = 0.017) but not with the risk of thrombosis, bleeding, or infections. The use of intravenous tocilizumab was not associated with changes in 30-day mortality in patients with COVID-19 severe respiratory impairment. Among the secondary outcomes there was less use of invasive ventilation in the tocilizumab group.
KW - Aged
KW - Antibodies, Monoclonal, Humanized/administration & dosage
KW - Betacoronavirus/immunology
KW - COVID-19
KW - Case-Control Studies
KW - Coronavirus Infections/complications
KW - Female
KW - Hospital Mortality
KW - Humans
KW - Infusions, Intravenous
KW - Interleukin-6/immunology
KW - Male
KW - Middle Aged
KW - Pandemics
KW - Pneumonia, Viral/complications
KW - Receptors, Interleukin-6/antagonists & inhibitors
KW - Respiratory Distress Syndrome/diagnosis
KW - Retrospective Studies
KW - SARS-CoV-2
KW - Severity of Illness Index
KW - Survival Analysis
KW - Treatment Outcome
U2 - 10.1016/j.jaut.2020.102511
DO - 10.1016/j.jaut.2020.102511
M3 - Article
C2 - 32713677
VL - 114
SP - 102511
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
ER -