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Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic

Background. Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called “cytokine storm” related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies,...

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Autores principales: Mahroum, Naim, Watad, Abdulla, Bridgewood, Charlie, Mansour, Muhammad, Nasr, Ahmad, Hussein, Amr, Khamisy-Farah, Rola, Farah, Raymond, Gendelman, Omer, Lidar, Merav, Shoenfeld, Yehuda, Amital, Howard, Kong, Jude Dzevela, Wu, Jianhong, Bragazzi, Nicola Luigi, McGonagle, Dennis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431489/
https://www.ncbi.nlm.nih.gov/pubmed/34501738
http://dx.doi.org/10.3390/ijerph18179149
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author Mahroum, Naim
Watad, Abdulla
Bridgewood, Charlie
Mansour, Muhammad
Nasr, Ahmad
Hussein, Amr
Khamisy-Farah, Rola
Farah, Raymond
Gendelman, Omer
Lidar, Merav
Shoenfeld, Yehuda
Amital, Howard
Kong, Jude Dzevela
Wu, Jianhong
Bragazzi, Nicola Luigi
McGonagle, Dennis
author_facet Mahroum, Naim
Watad, Abdulla
Bridgewood, Charlie
Mansour, Muhammad
Nasr, Ahmad
Hussein, Amr
Khamisy-Farah, Rola
Farah, Raymond
Gendelman, Omer
Lidar, Merav
Shoenfeld, Yehuda
Amital, Howard
Kong, Jude Dzevela
Wu, Jianhong
Bragazzi, Nicola Luigi
McGonagle, Dennis
author_sort Mahroum, Naim
collection PubMed
description Background. Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called “cytokine storm” related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies, mostly open label at the start of the pandemic. Methods: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until 20 July 2020 (PROSPERO CRD42020195690). Subgroup analyses and meta-regressions were performed. The impact of tocilizumab and concomitant corticosteroid therapy or tocilizumab alone versus standard of care (SOC) on the death rate, need for mechanical ventilation, ICU admission and bacterial infections were assessed. Results. Thirty-nine studies with 15,531 patients (3657 cases versus 11,874 controls) were identified. Unadjusted estimates (n = 28) failed to demonstrate a protective effect of tocilizumab on survival (OR 0.74 ([95%CI 0.55–1.01], p = 0.057), mechanical ventilation prevention (OR 2.21 [95%CI 0.53–9.23], p = 0.277) or prevention of ICU admission (OR 3.79 [95%CI 0.38–37.34], p = 0.254). Considering studies with adjusted, estimated, tocilizumab use was associated with mortality rate reduction (HR 0.50 ([95%CI 0.38–0.64], p < 0.001) and prevention of ICU admission (OR 0.16 ([95%CI 0.06–0.43], p < 0.001). Tocilizumab with concomitant steroid use versus SOC was protective with an OR of 0.49 ([95%CI 0.36–0.65], p < 0.05) as was tocilizumab alone versus SOC with an OR of 0.59 ([95%CI 0.34–1.00], p < 0.001). Risk of infection increased (2.36 [95%CI 1.001–5.54], p = 0.050; based on unadjusted estimates). Conclusion: Despite the heterogeneity of included studies and large number of preprint articles, our findings from the first eight of the pandemic in over 15,000 COVID-19 cases suggested an incremental efficacy of tocilizumab in severe COVID-19 that were confirmed by subsequent meta-analyses of large randomized trials of tocilizumab. This suggests that analysis of case-control studies and pre-print server data in the early stages of a pandemic appeared robust for supporting incremental benefits and lack of major therapeutic toxicity of tocilizumab for severe COVID-19.
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spelling pubmed-84314892021-09-11 Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic Mahroum, Naim Watad, Abdulla Bridgewood, Charlie Mansour, Muhammad Nasr, Ahmad Hussein, Amr Khamisy-Farah, Rola Farah, Raymond Gendelman, Omer Lidar, Merav Shoenfeld, Yehuda Amital, Howard Kong, Jude Dzevela Wu, Jianhong Bragazzi, Nicola Luigi McGonagle, Dennis Int J Environ Res Public Health Review Background. Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called “cytokine storm” related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies, mostly open label at the start of the pandemic. Methods: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until 20 July 2020 (PROSPERO CRD42020195690). Subgroup analyses and meta-regressions were performed. The impact of tocilizumab and concomitant corticosteroid therapy or tocilizumab alone versus standard of care (SOC) on the death rate, need for mechanical ventilation, ICU admission and bacterial infections were assessed. Results. Thirty-nine studies with 15,531 patients (3657 cases versus 11,874 controls) were identified. Unadjusted estimates (n = 28) failed to demonstrate a protective effect of tocilizumab on survival (OR 0.74 ([95%CI 0.55–1.01], p = 0.057), mechanical ventilation prevention (OR 2.21 [95%CI 0.53–9.23], p = 0.277) or prevention of ICU admission (OR 3.79 [95%CI 0.38–37.34], p = 0.254). Considering studies with adjusted, estimated, tocilizumab use was associated with mortality rate reduction (HR 0.50 ([95%CI 0.38–0.64], p < 0.001) and prevention of ICU admission (OR 0.16 ([95%CI 0.06–0.43], p < 0.001). Tocilizumab with concomitant steroid use versus SOC was protective with an OR of 0.49 ([95%CI 0.36–0.65], p < 0.05) as was tocilizumab alone versus SOC with an OR of 0.59 ([95%CI 0.34–1.00], p < 0.001). Risk of infection increased (2.36 [95%CI 1.001–5.54], p = 0.050; based on unadjusted estimates). Conclusion: Despite the heterogeneity of included studies and large number of preprint articles, our findings from the first eight of the pandemic in over 15,000 COVID-19 cases suggested an incremental efficacy of tocilizumab in severe COVID-19 that were confirmed by subsequent meta-analyses of large randomized trials of tocilizumab. This suggests that analysis of case-control studies and pre-print server data in the early stages of a pandemic appeared robust for supporting incremental benefits and lack of major therapeutic toxicity of tocilizumab for severe COVID-19. MDPI 2021-08-30 /pmc/articles/PMC8431489/ /pubmed/34501738 http://dx.doi.org/10.3390/ijerph18179149 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mahroum, Naim
Watad, Abdulla
Bridgewood, Charlie
Mansour, Muhammad
Nasr, Ahmad
Hussein, Amr
Khamisy-Farah, Rola
Farah, Raymond
Gendelman, Omer
Lidar, Merav
Shoenfeld, Yehuda
Amital, Howard
Kong, Jude Dzevela
Wu, Jianhong
Bragazzi, Nicola Luigi
McGonagle, Dennis
Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic
title Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic
title_full Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic
title_fullStr Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic
title_full_unstemmed Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic
title_short Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic
title_sort systematic review and meta-analysis of tocilizumab therapy versus standard of care in over 15,000 covid-19 pneumonia patients during the first eight months of the pandemic
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431489/
https://www.ncbi.nlm.nih.gov/pubmed/34501738
http://dx.doi.org/10.3390/ijerph18179149
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