Addition of Tocilizumab to the standard of care reduces mortality in severe COVID-19: A systematic review and meta-analysis

Abstract

Introduction: Tocilizumab is an anti-interleukin-6 antibody that has been used for the treatment of severe coronavirus disease 2019 (COVID-19). However, the concrete evidence of its benefit in reducing the mortality in severe COVID-19 is lacking. Therefore, we performed a systematic review and meta-analysis of relevant studies that compared the efficacy of Tocilizumab in severe COVID-19 vs. standard of care alone. Methods: Literature search for studies that compared Tocilizumab and Standard of care in the treatment of COVID-19 was done using major online databases from December 2019 to June 14th, 2020. Search words Tocilizumab, anti-interleukin-6 antibody, and COVID-19 or coronavirus 2019 in various combinations were used. Articles in the form of abstracts, letters without original data, case reports, and reviews were excluded. Data was gathered on an excel sheet, and statistical analysis was performed using Review Manager 5.3. Results: Five studies were eligible from 693 initial studies, including 3,641 patients (>2283 males). There were thirteen retrospective studies and three prospective studies. There were 2,488 patients in the standard of care group and 1,153 patients in the Tocilizumab group. The death rate in the tocilizumab group, 22.4% (258/1153), was lower than the standard of care group, 26.21% (652/2,488) (Pooled odds ratio 0.57 [95% CI 0.36-0.92] p=0.02). There was a significant heterogeneity (Inconsistency index= 80%) among the included studies. Conclusion: The addition of Tocilizumab to the standard of care reduces mortality in severe COVID-19. Larger randomized clinical trials are needed to validate these findings.

Efficacy of Tocilizumab in Covid 19: A metanalysis of case series studies

“…Eighteen studies assessed the mortality of COVID 19 patients following treatment with tocilizumab with an overall mortality rate 21% (251/1212)). The other metanalysis carried to assess efficacy of tocilizumab in case controlled and cohort studies also reported similar mortality rate of 22.4% (258/1,153) when compared to control [6]. However it is noteworthy to mention there was a substantial heterogeneity(I 2 =78.9%) in our study which is also similar to other published metanalysis (I 2 =80%) [6].…”

“…A characteristic feature of COVID-19 during its progression in severity is the cytokine storm (via interleukin-6, IL-6) which is responsible for secondary acute respiratory distress syndrome (ARDS) [2][3] [4]. ARDS is the most devastating complication of SARSCoV-2 with a higher death toll [5] [6]. The incidence of ARSD following COVID-19 is higher in severe cases.…”

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version)

“…Evidence summary A meta-analysis of 3641 patients including 16 studies (13 retrospective cohort studies and 3 prospective cohort studies) showed that adding tocilizumab (TCZ) to standard of care (SOC) may reduce the mortality of severe COVID-19 (Pooled OR = 0.57, 95% CI 0.36-0.92, P = 0.02), and it did not report any adverse effect. However, this evidence body was a lowquality evidence with degrading factors: more confounding factors (the difference in the age and comorbidities, variability in the follow-up period) and significant heterogeneity (I 2 = 80%) among the included studies [78].…”

Beneficial Effect of Corticosteroids in Preventing Mortality in Patients Receiving Tocilizumab to Treat Severe COVID-19 Illness

“…The first SRMA, published by Lan SH Zhang et al [13], included 7 studies, with no conclusive evidence that TCZ would provide any additional benefit to patients with severe COVID-19. The second, registered in the medRxiv repository by Boregowda et al [14] included 16 studies, concluding that the addition of TCZ to the SOC might reduce the mortality in severe COVID-19.…”