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

Abstract

Objective. This systematic review and meta-analysis was aimed to evaluate the efficacy and safety of tocilizumab (TCZ) in treating severe coronavirus disease 2019 . Methods. The electronic search was made using PubMed, Scopus, CEN-TRAL, and Google scholar to identify the retrospective observational reports. The studies published from 01 January 2020 to 30th October 2020. Participants were hospitalised COVID-19 patients. Interventions included tocilizumab versus placebo/standard of care. The comparison will be between TCZ versus standard of care (SOC)/ placebo. Inconsistency between the studies was evaluated with I 2 and quality of the evidences were evaluated by Newcastle-Ottawa scale. Results. Based 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 mortality (M-H, RE-OR -0.11(-0.18 --0.04) 95% CI, p=0.001, I 2 =88%) and increased the incidences of super-infections ) 95% CI, p=0.004, I 2 =47%). However, there is no significant difference in ICU admissions rate (M-H, RE-OR -0.06(-0.23-0.12), I 2 =93%), need for mechanical ventilation (M-H, RE-OR of 0.00(-0.06-0.07), I=74%), LOS , I 2 =100%), , I 2 =100%), and incidences of pulmonary thrombosis , I 2 =0%) compared to SOC/control. Conclusion.Based on cumulative lowto-moderate certainty evidence shows that TCZ could reduce the risk of mortality in hospitalised patients. However, there is no statistically significant difference observed between the TCZ and SOC/control groups in other parameters.

Risk factors associated with bacteremia in COVID-19 patients admitted to intensive care unit: a retrospective multicenter cohort study

“…In the COVID-19 era, infection control measures inevitably failed as the need to deal with an unprecedented health emergency arose [5]. Although the role of extensive use of immunosuppressants such as steroids, anti-IL1 and above all tocilizumab, is still debated, it could be speculated that it may have contributed to alter the balance of immune defenses by favoring the development of superinfections [18]. Some available evidence in literature, like the work published by Giacobbe et al, which includes all ICU admitted patients, seems to consider steroids and tocilizumab use as a factor associated to an increased risk of BSI development [10].…”

The association between tocilizumab therapy and the development of thrombosis in critically ill patients with COVID-19: a multicenter, cohort study

“…They found that there was no significant difference in the risk of VTE between patients with COVID-19 who received immunomodulatory agents and those who received standard care (OR 0.52, 95%CI 0.22–1.20; I 2 = 6%) 22 . In addition, Viswanatha et al 21 in a meta-analysis that included 5686 patients with COVID-19 has shown a non-significant difference in the occurrence of pulmonary embolism during the TCZ therapy compared to the standard of care (OR 1.01, 95%CI 0.45–2.26, I 2 = 0%). Likewise, our analysis did not find any significant increase in the risk of thrombosis for patients with COVID-19 who were treated with TCZ.…”

“…While outcomes that were more subjectively measured, such as disease activity, were thought to be susceptible to bias 23 . Moreover, the Viswanatha et al 21 meta-analysis found that TCZ therapy was associated with a lower risk of mortality compared to the standard of care (OR − 0.11, 95%CI − 0.18 to − 0.04), but with significant heterogeneity among studies (I 2 = 88%, p = 0.001). Similarly, our study revealed that the use of TCZ was associated with a lower risk of mortality in critically ill patients when compared to the standard care; patients treated with TCZ had a 43% lower risk of 30-day mortality and a 33% lower risk of in-hospital mortality.…”

“…In contrast, a systematic review and meta-analysis that evaluated the efficacy and safety of TCZ in the treatment of COVID-19 illustrated no significant difference in pulmonary thrombosis rates between TCZ and the control group 21 . An additional systematic review and meta-analysis demonstrated a tendency toward fewer VTEs in individuals using IL-6 inhibitors.…”

Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience

“…Tocilizumab (TCZ) is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R), applied in severe COVID-19 with hyperinflammation since early 2020 [ 19 , 20 , 21 ]. It was proven to reduce in-hospital mortality, the need for mechanical ventilation, or intensive care unit (ICU) transfer [ 22 , 23 , 24 , 25 , 26 ]. It was approved for use in COVID-19 by the European Medicines Agency (EMA) in December 2021 and one year later by the Food and Drug Administration (FDA).…”