Efficacy and Safety of Tocilizumab in the Treatment of SARS-CoV-2: A Systematic Review and Meta-analysis
Background: Cytokine storm is the main cause of mortality in COVID-19. Tocilizumab, an IL-6 inhibitor, is being tested for its therapeutic potential in this condition. To evaluate the efficacy and safety of Tocilizumab in comparison to Standard therapy in the treatment of COVID-19 in adult patients.
Methods: Using Medline (via PubMed), The Cochrane Central Register of Controlled Trials, preprint server (medRxiv) and clinicaltrials.gov, a final search was conducted on 26th June 2020. All types of clinical studies (prospective or retrospective cohort studies, observational case-control studies, clinical trials) aiming to evaluate the role of Tocilizumab in the treatment of patients with COVID-19 were considered eligible for this systematic review. Tocilizumab was considered as the intervention group and standard of care or drugs other than tocilizumab as control group. Meta-analysis was performed by Cochrane review manager 5 (RevMan) version 5.3. For quality assessment, ROBINS-I (The Risk Of Bias In Non-randomised studies – of Interventions) assessment tool for observational studies was used. The overall quality of evidence for each of the outcomes was assessed using the GRADE Pro GDT.
Results: Out of 362 records identified, 13 studies were included in qualitative and quantitative analysis. Tocilizumab treatment was associated with 46% decrease in probability of mortality rate [Adjusted HR = 0.54 (95% CI = 0.44-0.68), p<0.00001; I2=74%] and 66% odds decrease in progression of disease [OR = 0.34 (95% CI = 0.21 – 0.55), p<0.0001; I2=76%] compared to control. However, there was no difference in hospital discharge [OR = 1.35 (95% CI = 0.84 – 2.18), p=0.22; I2=22%] and clinical improvement [OR = 1.02 (95% CI = 0.61 – 1.69), p=0.95; I2=84%] with tocilizumab. There was statistically significant increase in risk of secondary bacteraemia [OR = 2.75 (95% CI = 1.86 – 4.06), p< 0.00001] and superinfections [OR = 2.93 (95% CI = 1.92 – 4.46), p< 0.00001].
Conclusions: With current evidence on efficacy and safety of tocilizumab, we recommend use of tocilizumab treatment for moderate to severe COVID-19 patients caused by SARS-CoV-2, along with caution for superinfections.
Systematic review registration: PROSPERO registration number: CRD42020189517
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ROBINS-I: Risk of bias in observational studies evaluating tocilizumab in the treatment of COVID-19 (Weighted Summary plot)
Rate of hospital discharge of tocilizumab vs control treatment
Number of patients showing clinical improvement of tocilizumab vs control treatment
Funnel plot depicting publication bias for studies included in the review
Posted 25 Aug, 2020
Efficacy and Safety of Tocilizumab in the Treatment of SARS-CoV-2: A Systematic Review and Meta-analysis
Posted 25 Aug, 2020
Background: Cytokine storm is the main cause of mortality in COVID-19. Tocilizumab, an IL-6 inhibitor, is being tested for its therapeutic potential in this condition. To evaluate the efficacy and safety of Tocilizumab in comparison to Standard therapy in the treatment of COVID-19 in adult patients.
Methods: Using Medline (via PubMed), The Cochrane Central Register of Controlled Trials, preprint server (medRxiv) and clinicaltrials.gov, a final search was conducted on 26th June 2020. All types of clinical studies (prospective or retrospective cohort studies, observational case-control studies, clinical trials) aiming to evaluate the role of Tocilizumab in the treatment of patients with COVID-19 were considered eligible for this systematic review. Tocilizumab was considered as the intervention group and standard of care or drugs other than tocilizumab as control group. Meta-analysis was performed by Cochrane review manager 5 (RevMan) version 5.3. For quality assessment, ROBINS-I (The Risk Of Bias In Non-randomised studies – of Interventions) assessment tool for observational studies was used. The overall quality of evidence for each of the outcomes was assessed using the GRADE Pro GDT.
Results: Out of 362 records identified, 13 studies were included in qualitative and quantitative analysis. Tocilizumab treatment was associated with 46% decrease in probability of mortality rate [Adjusted HR = 0.54 (95% CI = 0.44-0.68), p<0.00001; I2=74%] and 66% odds decrease in progression of disease [OR = 0.34 (95% CI = 0.21 – 0.55), p<0.0001; I2=76%] compared to control. However, there was no difference in hospital discharge [OR = 1.35 (95% CI = 0.84 – 2.18), p=0.22; I2=22%] and clinical improvement [OR = 1.02 (95% CI = 0.61 – 1.69), p=0.95; I2=84%] with tocilizumab. There was statistically significant increase in risk of secondary bacteraemia [OR = 2.75 (95% CI = 1.86 – 4.06), p< 0.00001] and superinfections [OR = 2.93 (95% CI = 1.92 – 4.46), p< 0.00001].
Conclusions: With current evidence on efficacy and safety of tocilizumab, we recommend use of tocilizumab treatment for moderate to severe COVID-19 patients caused by SARS-CoV-2, along with caution for superinfections.
Systematic review registration: PROSPERO registration number: CRD42020189517
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