Efficacy and safety of tocilizumab in the management of COVID-19: A systematic review and meta-analysis of observational studies

Abstract

BackgroundThis systematic review and meta-analysis was aimed to evaluate the therapeutic benefits and safety of tocilizumab (TCZ) in treating severe coronavirus disease 2019 (COVID-19) and associated health complications.MethodsThe electronic search was performed using PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials (RCTs), and Google scholar databases to identify the retrospective observational reports. The studies published from 01 January 2020 to 30th September 2020 involving comparison of TCZ group with SOC/control treatment group were included. The studies included in this work involve RT-PCR confirmed cases of COVID-19 (Population), having tocilizumab and corresponding SOC/control as interventions (Intervention), comparison between tocilizumab versus SOC/control (Comparison) for the parameter of interest. Mortality, incidences of ICU admission, need of mechanical ventilation (MV), length of stay in the hospital (LOS), and length of stay in the ICU (LOS-ICU), and the incidences of super-infection, bacteraemia, fugleman, pneumonia, and pulmonary thrombosis were evaluated as the primary outcomes. The comparison will be between TCZ versus standard of care (SOC)/placebo.ResultsBased on the inclusion criteria there were 24 retrospective studies involving 5686 subjects were included. The outcomes of the meta-analysis have revealed that the TCZ has reduced the mortality (Mantel-Haenszel (M-H), random effects risk difference (RE-RD) of - 0.11 (-0.18 to -0.04), at 95% CI, p = 0.001, I2 = 88%) and increased the incidences of super-infections (M-H, RE-Risk ratio (RR) of 1.49 (1.13 to 1.96) at 95% CI, p=0.004, I2 = 47%). However, there is no significant difference in ICU admissions rate (M-H, RE-RD of -0.06 (-0.23 to 0.12) at 95% CI, p=0.54, I2 = 93%), need of MV (M-H, RE-RD of 0.00 (-0.06 to 0.07) at 95% CI, p=0.96, I2 = 74%), LOS (Inverse variance (IV): -2.86 (-0.91 to 3.38) at 95% CI, p=0.37, I2 = 100%), LOS-ICU (IV: -3.93 (-12.35 to 4.48) at 95% CI, p=0.36, I2 = 100%), and incidences of pulmonary thrombosis (M-H, fixed effect odds ratio (FE-OR) of 1.01 (0.45 to 2.26) at 95% CI, p=0.99, I2 = 0%) compared to SOC/control.ConclusionThis meta-analysis was performed using retrospective clinical reports on the use of tocilizumab in COVID-19 and based on the outcomes of the meta-analysis we can conclude that administration of TCZ would reduce the risk of mortality, and however there is no much difference observed between the TCZ and SOC/control groups in other parameters such as ICU admission rate, need of mechanical ventilation and length of hospital stay (ICU and Non-ICU). On the other hand, TCZ treated subjects possess higher chances of super-infections and pneumonia compared with SOC/control group. However, there is a need for multi-centric randomized trials to determine the potential therapeutic role of TCZ in mitigating COVID-19 and associated health complications.

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

“…After evaluating the other 92 articles for eligibility, 42 were excluded for the following reasons: one study investigated tocilizumab combined with another IL‐6 inhibitor, 20 two discussed therapies other than tocilizumab, 21,22 37 were not systematic reviews, 23–59 and two were systematic reviews of preclinical or animal studies 60,61 . Finally, 50 articles met the eligibility criteria and were included in the present umbrella review 6,28,62–109 (Figure 1).…”

The response to COVID 19 across countries and the implications for future pandemics

“…In fact, to date, only dexamethasone has been shown in large well conducted clinical trials to benefit patients on respiratory support in hospital with COVID-19 66 . There is also increasing evidence to support the use of medicines such as tocilizumab [67][68][69] .…”