Efficacy of tocilizumab in COVID‐19: A systematic review and meta‐analysis

Aziz, Muhammad; Haghbin, Hossein; Sitta, Emad Abu; Nawras, Yusuf; Fatima, Rawish; Sharma, Sachit; Lee‐Smith, Wade; Duggan, Joan; Kammeyer, Joel; Hanrahan, Jennifer; Assaly, Ragheb

doi:10.1002/jmv.26509

Cited by 91 publications

(95 citation statements)

References 45 publications

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“…The most recent systematic reviews on the use of TCZ for COVID-19 identified clinical trials without data synthesis (Cortegiani et al, 2020) and performed a large meta-analysis of controlled trials but did not address issues with the individual studies (Aziz et al, 2020). Therefore, this systematic review will synthesize the evidence from individual case-control studies, analyze uncontrolled trials and evaluate their methods to Figure 3 IL-6 pathway and TCZ mechanism of action.…”

Section: Il-6 Inhibitor Tocilizumabmentioning

confidence: 99%

The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review

Kaye

Siegel

2020

PeerJ

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Background In the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19. Evaluating the efficacy existing drugs may expedite the development of such therapeutics. Severe COVID-19 is largely the result of a dysregulated immune response characterized by lymphocytopenia, neutrophilia and critical hypercytokinemia, or “cytokine storm,” which is largely mediated by the cytokine interleukin-6 (IL-6). The IL-6 inhibitor tocilizumab (TCZ) could potentially suppress the effects of the pro-inflammatory cytokine and thereby lower mortality from the disease. This systematic analysis aimed to investigate and synthesize existing evidence for the efficacy of TCZ in reducing COVID-19 mortality. Methodology PubMed and SearchWorks searches were performed to locate clinical studies with primary data on TCZ treatment for severe COVID-19. Sixteen case-control studies comparing mortality between TCZ and standard of care (SOC) were identified for quantitative synthesis. The systematic analysis was pre-approved through PROSPERO (CRD42020193479). Results Combined mortality for the TCZ-treated and SOC groups were 26.0% and 43.4% respectively. In all but one of the studies, the odds ratio of mortality from COVID-19 pointed towards lower fatality with TCZ vs the SOC. A combined random effects odds ratio calculation yielded an odds ratio of 0.453 (95% CI [0.376–0.547], p < 0.001). Additionally, 18 uncontrolled trials were identified for qualitative analysis producing a raw combined mortality rate of 16.0%. Conclusions Important caveats to this research include the lack of prospective randomized control trials and the absence of data from the large COVATA study from the published literature. However, results from this systematic analysis of published research provide positive evidence for the potential efficacy of TCZ to treat severe COVID-19, validating the ethical basis and merit of ongoing randomized controlled clinical trials.

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Section: Il-6 Inhibitor Tocilizumabmentioning

confidence: 99%

The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review

Kaye

Siegel

2020

PeerJ

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“…A previously published meta-analysis showed that COVID-19 patients treated with tocilizumab had reduced mortality, less need for mechanical ventilation, improved respiratory function, rapid defervescence, and successful discharge compared with the control group, especially when the subgroup analysis was restricted to studies that only included patients with severe COVID‐19 based on the clinical picture and laboratory parameters [21] , [22] , [23] . Our study is consistent with these studies, and the samples were restricted to severe COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Experience of using tocilizumab for treatment in Indonesian patients with severe COVID-19

et al. 2021

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“…The most recent systematic reviews on the use of TCZ for COVID-19 identified clinical trials without data synthesis 26 and performed a large meta-analysis of controlled trials but did not address issues with the individual studies. 27 Therefore, this systematic review will synthesize the evidence from individual case-control studies, analyze uncontrolled trials and evaluate their methods to determine whether the drug is potentially effective at reducing severe COVID-19-related mortality, thus corroborating the logic for continuing RCTs to evaluate the potential use of IL-6 inhibitors.…”

Section: Il-6 Inhibitor Tocilizumabmentioning

confidence: 99%

Peer Review #1 of "The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review (v0.1)"

Kamat¹

2020

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Background: In the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19. Evaluating the efficacy existing drugs may expedite the development of such therapeutics. Severe COVID-19 is largely the result of a dysregulated immune response characterized by lymphocytopenia, neutrophilia and critical hypercytokinemia, or "cytokine storm," which is largely mediated by the cytokine interleukin-6 (IL-6). The IL-6 inhibitor tocilizumab (TCZ) could potentially suppress the effects of the pro-inflammatory cytokine and thereby lower mortality from the disease. This systematic analysis aimed to investigate and synthesize existing evidence for the efficacy of TCZ in reducing COVID-19 mortality. Methodology: PubMed and SearchWorks searches were performed to locate clinical studies with primary data on TCZ treatment for severe COVID-19. Sixteen case-control studies comparing mortality between TCZ and standard of care (SOC) were identified for quantitative synthesis. The systematic analysis was pre-approved through PROSPERO (CRD42020193479). Results: Combined mortality for the TCZ-treated and SOC groups were 26.0% and 43.4% respectively. In all but one of the studies, the odds ratio of mortality from COVID-19 pointed towards lower fatality with TCZ versus the SOC. A combined random effects odds ratio calculation yielded an odds ratio of 0.453 (95% CI 0.376-0.547, p<0.001). Additionally, eighteen uncontrolled trials were identified for qualitative analysis producing a raw combined mortality rate of 16.0%. Conclusions: Important caveats to this research include the lack of prospective randomized control trials (RCTs) and the absence of data from the large COVATA study from the published literature. However, results from this systematic analysis of published research provide positive evidence for the potential efficacy of TCZ to treat severe COVID-19, validating the ethical basis and merit of ongoing randomized controlled clinical trials.

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Efficacy of tocilizumab in COVID‐19: A systematic review and meta‐analysis

Cited by 91 publications

References 45 publications

The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review

The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review

Experience of using tocilizumab for treatment in Indonesian patients with severe COVID-19

Peer Review #1 of "The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review (v0.1)"

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