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. 2022 Nov;32(6):e2388.
doi: 10.1002/rmv.2388. Epub 2022 Aug 27.

Efficacy of tocilizumab in the treatment of COVID-19: An umbrella review

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Efficacy of tocilizumab in the treatment of COVID-19: An umbrella review

Mohammad Mahdi Rezaei Tolzali et al. Rev Med Virol. 2022 Nov.

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.

Keywords: COVID-19; SARS-CoV-2; efficacy; interleukin 6; tocilizumab; umbrella review.

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Conflict of interest statement

No conflict of interest declared.

Figures

FIGURE 1
FIGURE 1
Study selection process
FIGURE 2
FIGURE 2
Forest plots of the pooled estimates for hazard ratios on the association between tocilizumab administration and risk of clinical failure (i.e. intubation, admission to ICU, or death) by study type. hazard ratio (HR); confidence interval (CI); DerSimonian and Laird (DL); randomized controlled trial (RCT)
FIGURE 3
FIGURE 3
Forest plots of the summary effects for risk ratios on the association between tocilizumab administration and risk of clinical failure (i.e. intubation, admission to ICU, or death) by study type. risk ratio (RR); confidence interval (CI); DerSimonian and Laird (DL); randomized controlled trial (RCT)
FIGURE 4
FIGURE 4
Forest plots of the pooled estimates for hazard ratios on the association between tocilizumab administration and risk of overall mortality by study type. hazard ratio (HR); confidence interval (CI); DerSimonian and Laird (DL); randomized controlled trial (RCT)
FIGURE 5
FIGURE 5
Forest plots of the summary effects for risk ratios on the association between tocilizumab administration and risk of overall mortality by study type. risk ratio (RR); confidence interval (CI); DerSimonian and Laird (DL); randomized controlled trial (RCT)

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