Beneficial and Harmful Outcomes of Tocilizumab in Severe COVID-19: A Systematic Review and Meta-Analysis

Rubio-Rivas, M.; Mora-Lujan, J. M.; Montero, A.; Homs, N. A.; Rello, J.; Corbella, X.

Background: Pending for randomized control trials, the use of tocilizumab (TCZ) in COVID-19 is based on observational studies and remains controversial. Purpose: To summarize evidence about the effect of TCZ to treat severe COVID-19. Data sources: PubMed (via MEDLINE), Scopus, and medRxiv repository databases from 1 January to 21 August 2020. Study Selection: Observational studies in any language reporting efficacy and safety outcomes of TCZ use in hospitalized adults with COVID-19. Data Extraction: Independent, dually performed data extraction and quality assessments. Data synthesis: Of 57 eligible studies, 27 were controlled and 30 were not. The overall included patients were 8,128: 4,021 treated with TCZ, in addition to standard of care (SOC), and 4,107 only receiving SOC. The pooled mortality was lower in the TCZ-group vs. the control group, with a relative risk (RR) of 0.73 (95%CI 0.57-0.93; p=0.010). The overall NNT to avoid one death was 20. In hospital wards, patients in the TCZ-group were transferred to intensive care unit (ICU) in a higher proportion than those in the control group; however, ICU mortality of the TCZ-group was lower than in the control group. Secondary infections occurred in a higher proportion in TCZ-treated patients. Among survivors, the length of stay was similar in both groups. Limitations: Conclusions should be considered as weak evidence since they are based on observational studies, most of them retrospective. A variety of factors influencing the indication and effect of TCZ could not be evaluated in-depth. Conclusions: TCZ to seem beneficial in preventing in-hospital mortality in severe, non-critically ill COVID-19 patients. Conversely, patients receiving TCZ appear to be at higher risk for secondary infections, especially those admitted to ICU.