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Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients.
J Autoimmun. 2020 11; 114:102511.JA

Abstract

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.

Authors+Show Affiliations

Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (MI), Italy; Internal Medicine, Humanitas Gavazzeni, Bergamo (BG), Italy.Internal Medicine, Humanitas Gavazzeni, Bergamo (BG), Italy.General Medicine and Nephrology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.Internal Medicine, Humanitas Gavazzeni, Bergamo (BG), Italy.Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.Scientific Direction, Humanitas Gavazzeni, Bergamo (BG), Italy.Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.Anesthesiology and Intensive Care, Humanitas Gavazzeni, Bergamo (BG), Italy.General Medicine and Hepatology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.Medical Oncology, Humanitas Gavazzeni, Bergamo (BG), Italy.Medical Oncology, Humanitas Gavazzeni, Bergamo (BG), Italy.General Medicine and Pulmonology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.Medical Direction, Humanitas Gavazzeni, Bergamo (BG), Italy.Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (MI), Italy; General Medicine and Hepatology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (MI), Italy; General Medicine and Hepatology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.Pharmacy, Humanitas Gavazzeni, Bergamo (BG), Italy.Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (MI), Italy; General Medicine and Gastroenterology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.General Medicine and Gastroenterology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.General Medicine and Nephrology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.General Medicine and Nephrology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy.Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (MI), Italy; Anesthesiology andIntensive Care, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy. Electronic address: maurizio.cecconi@hunimed.eu.Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (MI), Italy; Cardiology, Humanitas Gavazzeni, Bergamo (BG), Italy.Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (MI), Italy; Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy. Electronic address: carlo.selmi@hunimed.eu.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32713677

Citation

Canziani, Lorenzo M., et al. "Interleukin-6 Receptor Blocking With Intravenous Tocilizumab in COVID-19 Severe Acute Respiratory Distress Syndrome: a Retrospective Case-control Survival Analysis of 128 Patients." Journal of Autoimmunity, vol. 114, 2020, p. 102511.
Canziani LM, Trovati S, Brunetta E, et al. Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients. J Autoimmun. 2020;114:102511.
Canziani, L. M., Trovati, S., Brunetta, E., Testa, A., De Santis, M., Bombardieri, E., Guidelli, G., Albano, G., Folci, M., Squadroni, M., Beretta, G. D., Ciccarelli, M., Castoldi, M., Lleo, A., Aghemo, A., Vernile, L., Malesci, A., Omodei, P., Angelini, C., ... Selmi, C. (2020). Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients. Journal of Autoimmunity, 114, 102511. https://doi.org/10.1016/j.jaut.2020.102511
Canziani LM, et al. Interleukin-6 Receptor Blocking With Intravenous Tocilizumab in COVID-19 Severe Acute Respiratory Distress Syndrome: a Retrospective Case-control Survival Analysis of 128 Patients. J Autoimmun. 2020;114:102511. PubMed PMID: 32713677.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients. 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, AU - ,, Y1 - 2020/07/08/ PY - 2020/06/16/received PY - 2020/06/22/revised PY - 2020/06/24/accepted PY - 2020/7/28/pubmed PY - 2020/10/28/medline PY - 2020/7/28/entrez KW - Interstitial pneumonia KW - Intubation KW - SARS-Cov-2 SP - 102511 EP - 102511 JF - Journal of autoimmunity JO - J Autoimmun VL - 114 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. SN - 1095-9157 UR - https://www.unboundmedicine.com/medline/citation/32713677/Interleukin_6_receptor_blocking_with_intravenous_tocilizumab_in_COVID_19_severe_acute_respiratory_distress_syndrome:_A_retrospective_case_control_survival_analysis_of_128_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0896-8411(20)30133-5 DB - PRIME DP - Unbound Medicine ER -