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Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review
Tocilizumab is an interleukin (IL)‐6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID‐19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID‐19, and to provide an overview of all systematic revi...
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Published in: | Reviews in medical virology 2022-11, Vol.32 (6), p.e2388-n/a |
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creator | Rezaei Tolzali, Mohammad Mahdi Noori, Maryam Shokri, Pourya Rahmani, Shayan Khanzadeh, Shokoufeh Nejadghaderi, Seyed Aria Fazlollahi, Asra Sullman, Mark J. M. Singh, Kuljit Kolahi, Ali‐Asghar Arshi, Shahnam Safiri, Saeid |
description | Tocilizumab is an interleukin (IL)‐6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID‐19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID‐19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: ‘SARS‐CoV‐2’, ‘COVID‐19’, ‘tocilizumab’, ‘RHPM‐1’, ‘systematic review’, and ‘meta‐analysis’. Studies were included if they were systematic reviews (with or without meta‐analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID‐19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61–0.93), deaths (RR 0.78; 95%CI, 0.71–0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64–0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43–0.63). In addition, tocilizumab substantially increased the number of ventilator‐free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51–6.25). Furthermore, lymphocyte count (WMD 0.26 × 109/L; 95%CI, 0.14–0.37), IL‐6 (WMD 176.99 pg/mL; 95%CI, 76.34–277.64) and D‐dimer (WMD 741.08 ng/mL; 95%CI, 109.42–1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD −30.88 U/L; 95%CI, −51.52, −10.24) and C‐reactive protein (CRP) (WMD ‐104.83 mg/L; 95%CI, −133.21, −76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID‐19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID‐19. |
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M. ; Singh, Kuljit ; Kolahi, Ali‐Asghar ; Arshi, Shahnam ; Safiri, Saeid</creator><creatorcontrib>Rezaei Tolzali, Mohammad Mahdi ; Noori, Maryam ; Shokri, Pourya ; Rahmani, Shayan ; Khanzadeh, Shokoufeh ; Nejadghaderi, Seyed Aria ; Fazlollahi, Asra ; Sullman, Mark J. M. ; Singh, Kuljit ; Kolahi, Ali‐Asghar ; Arshi, Shahnam ; Safiri, Saeid</creatorcontrib><description>Tocilizumab is an interleukin (IL)‐6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID‐19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID‐19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: ‘SARS‐CoV‐2’, ‘COVID‐19’, ‘tocilizumab’, ‘RHPM‐1’, ‘systematic review’, and ‘meta‐analysis’. Studies were included if they were systematic reviews (with or without meta‐analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID‐19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61–0.93), deaths (RR 0.78; 95%CI, 0.71–0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64–0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43–0.63). In addition, tocilizumab substantially increased the number of ventilator‐free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51–6.25). Furthermore, lymphocyte count (WMD 0.26 × 109/L; 95%CI, 0.14–0.37), IL‐6 (WMD 176.99 pg/mL; 95%CI, 76.34–277.64) and D‐dimer (WMD 741.08 ng/mL; 95%CI, 109.42–1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD −30.88 U/L; 95%CI, −51.52, −10.24) and C‐reactive protein (CRP) (WMD ‐104.83 mg/L; 95%CI, −133.21, −76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID‐19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID‐19.</description><identifier>ISSN: 1052-9276</identifier><identifier>ISSN: 1099-1654</identifier><identifier>EISSN: 1099-1654</identifier><identifier>DOI: 10.1002/rmv.2388</identifier><identifier>PMID: 36029180</identifier><language>eng</language><publisher>England: Wiley Periodicals Inc</publisher><subject>C-Reactive Protein ; Cell number ; Coronaviruses ; COVID-19 ; COVID-19 Drug Treatment ; efficacy ; Humans ; Interleukin 6 ; Intubation ; L-Lactate dehydrogenase ; Lactic acid ; Lymphocytes ; Mechanical ventilation ; Meta-analysis ; Monoclonal antibodies ; Patients ; Respiration, Artificial ; Review ; SARS-CoV-2 ; Severe acute respiratory syndrome coronavirus 2 ; tocilizumab ; Treatment Outcome ; umbrella review</subject><ispartof>Reviews in medical virology, 2022-11, Vol.32 (6), p.e2388-n/a</ispartof><rights>2022 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4388-441abf35775b111a13652f794424a5341bc2ac81b7286cc8ae8583557e1b09133</citedby><cites>FETCH-LOGICAL-c4388-441abf35775b111a13652f794424a5341bc2ac81b7286cc8ae8583557e1b09133</cites><orcidid>0000-0001-7986-9072 ; 0000-0002-8692-9720 ; 0000-0003-4515-9587 ; 0000-0003-0103-7596 ; 0000-0003-0178-3732</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,778,782,883,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36029180$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rezaei Tolzali, Mohammad Mahdi</creatorcontrib><creatorcontrib>Noori, Maryam</creatorcontrib><creatorcontrib>Shokri, Pourya</creatorcontrib><creatorcontrib>Rahmani, Shayan</creatorcontrib><creatorcontrib>Khanzadeh, Shokoufeh</creatorcontrib><creatorcontrib>Nejadghaderi, Seyed Aria</creatorcontrib><creatorcontrib>Fazlollahi, Asra</creatorcontrib><creatorcontrib>Sullman, Mark J. M.</creatorcontrib><creatorcontrib>Singh, Kuljit</creatorcontrib><creatorcontrib>Kolahi, Ali‐Asghar</creatorcontrib><creatorcontrib>Arshi, Shahnam</creatorcontrib><creatorcontrib>Safiri, Saeid</creatorcontrib><title>Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review</title><title>Reviews in medical virology</title><addtitle>Rev Med Virol</addtitle><description>Tocilizumab is an interleukin (IL)‐6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID‐19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID‐19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: ‘SARS‐CoV‐2’, ‘COVID‐19’, ‘tocilizumab’, ‘RHPM‐1’, ‘systematic review’, and ‘meta‐analysis’. Studies were included if they were systematic reviews (with or without meta‐analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID‐19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61–0.93), deaths (RR 0.78; 95%CI, 0.71–0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64–0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43–0.63). In addition, tocilizumab substantially increased the number of ventilator‐free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51–6.25). Furthermore, lymphocyte count (WMD 0.26 × 109/L; 95%CI, 0.14–0.37), IL‐6 (WMD 176.99 pg/mL; 95%CI, 76.34–277.64) and D‐dimer (WMD 741.08 ng/mL; 95%CI, 109.42–1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD −30.88 U/L; 95%CI, −51.52, −10.24) and C‐reactive protein (CRP) (WMD ‐104.83 mg/L; 95%CI, −133.21, −76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID‐19 patients. 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M.</au><au>Singh, Kuljit</au><au>Kolahi, Ali‐Asghar</au><au>Arshi, Shahnam</au><au>Safiri, Saeid</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review</atitle><jtitle>Reviews in medical virology</jtitle><addtitle>Rev Med Virol</addtitle><date>2022-11</date><risdate>2022</risdate><volume>32</volume><issue>6</issue><spage>e2388</spage><epage>n/a</epage><pages>e2388-n/a</pages><issn>1052-9276</issn><issn>1099-1654</issn><eissn>1099-1654</eissn><abstract>Tocilizumab is an interleukin (IL)‐6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID‐19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID‐19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: ‘SARS‐CoV‐2’, ‘COVID‐19’, ‘tocilizumab’, ‘RHPM‐1’, ‘systematic review’, and ‘meta‐analysis’. Studies were included if they were systematic reviews (with or without meta‐analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID‐19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61–0.93), deaths (RR 0.78; 95%CI, 0.71–0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64–0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43–0.63). In addition, tocilizumab substantially increased the number of ventilator‐free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51–6.25). Furthermore, lymphocyte count (WMD 0.26 × 109/L; 95%CI, 0.14–0.37), IL‐6 (WMD 176.99 pg/mL; 95%CI, 76.34–277.64) and D‐dimer (WMD 741.08 ng/mL; 95%CI, 109.42–1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD −30.88 U/L; 95%CI, −51.52, −10.24) and C‐reactive protein (CRP) (WMD ‐104.83 mg/L; 95%CI, −133.21, −76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID‐19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID‐19.</abstract><cop>England</cop><pub>Wiley Periodicals Inc</pub><pmid>36029180</pmid><doi>10.1002/rmv.2388</doi><tpages>22</tpages><orcidid>https://orcid.org/0000-0001-7986-9072</orcidid><orcidid>https://orcid.org/0000-0002-8692-9720</orcidid><orcidid>https://orcid.org/0000-0003-4515-9587</orcidid><orcidid>https://orcid.org/0000-0003-0103-7596</orcidid><orcidid>https://orcid.org/0000-0003-0178-3732</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | C-Reactive Protein Cell number Coronaviruses COVID-19 COVID-19 Drug Treatment efficacy Humans Interleukin 6 Intubation L-Lactate dehydrogenase Lactic acid Lymphocytes Mechanical ventilation Meta-analysis Monoclonal antibodies Patients Respiration, Artificial Review SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 tocilizumab Treatment Outcome umbrella review |
title | Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review |
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