Addition of Tocilizumab to the Standard of Care Reduces Mortality in Severe COVID-19: A Systematic Review and Meta-Analysis

Abstract

Introduction: Tocilizumab (TCZ) is an anti-interleukin-6 antibody that has been used for the treatment of severe coronavirus disease 2019 (COVID-19). However, concrete evidence of its benefit in reducing mortality in severe COVID-19 is lacking. Therefore, we performed a systematic review and meta-analysis of relevant studies that compared the efficacy of TCZ in severe COVID-19 vs. standard of care (SOC) alone. Methods: A 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 14, 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 were gathered on an Excel sheet, and statistical analysis was performed using Review Manager 5.3. Results: Sixteen studies were eligible from 693 initial studies, including 3,641 patients (64% males). There were 13 retrospective studies and three prospective studies. There were 2,488 patients in the SOC group (61.7%) and 1,153 patients (68.7%) in the TCZ group. The death rate in the TCZ group, 22.4% (258/1,153), was lower than in the SOC 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 TCZ to the SOC might reduce mortality in severe COVID-19. More extensive randomized clinical trials are needed to validate these findings.

Understanding the Co-Epidemic of Obesity and COVID-19: Current Evidence, Comparison with Previous Epidemics, Mechanisms, and Preventive and Therapeutic Perspectives

“…Of note, NLRP3 expression is upregulated in obesity and plays a pivotal role in the activation and recruitment of macrophages [113]. Interestingly, the addition of the antirheumatic agents that block IL-1, IL-6, and inflammasome actions, such as anakinra, tocilizumab, and colchicine, in the standard of care in severe COVID-19 has shown promising results in nonrandomized clinical trials [114][115][116][117]. However, two large RCTs of anti-IL-6 receptor antibody treatment did not document a survival benefit in severe COVID-19 [118,119].…”

Revised Korean Society of Infectious Diseases/National Evidence-based Healthcarea Collaborating Agency Guidelines on the Treatment of Patients with COVID-19

“…In six recently published systematic reviews and meta-analyses, the effects of tocilizumab on mortality in patients with severe COVID-19 were not consistent. In four studies, tocilizumab treatment significantly reduced the mortality rate [ 155 156 157 158 ], while opposite findings were observed in two other studies [ 159 160 ].…”

Case Discussion and Literature Review: Cancer Immunotherapy, Severe Immune-Related Adverse Events, Multi-Inflammatory Syndrome, and Severe Acute Respiratory Syndrome Coronavirus 2

“…In a meta-analysis of 16 studies and 3,641 patients, there was a statistically significant reduction in the mortality of patients with severe COVID19 when treated with TCZ, but this difference was not significant if patients received corticosteroids. Given the heterogeneity across studies however, it is difficult to draw any firm conclusions regarding the use of TCZ from this meta-analysis ( 26 ). Given its ability to decrease the cytokine storm TCZ has also been included for consideration for the treatment of refractory or severe MIS (C/A) ( 27 ).…”