Current best evidence for clinical care (more info)
OBJECTIVE: We aimed to perform a meta-analysis of randomized controlled trials (RCTs) to summarize the overall effect of tocilizumab on the risk of mortality among patients with coronavirus disease 2019 (COVID-19).
METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Google Scholar, and medRxiv (preprint repository) databases (up to 7 January 2021). Pooled effect sizes with 95% confidence interval (CI) were generated using random-effects and inverse variance heterogeneity models. The risk of bias of the included RCTs was appraised using version 2 of the Cochrane risk-of-bias tool for randomized trials.
RESULTS: Six RCTs were included: two trials with an overall low risk of bias and four trials had some concerns regarding the overall risk of bias. Our meta-analysis did not find significant mortality benefits with the use of tocilizumab among patients with COVID-19 relative to non-use of tocilizumab (pooled hazard ratio = 0.83; 95% CI 0.66-1.05, n = 2,057). Interestingly, the estimated effect of tocilizumab on the composite endpoint of requirement for mechanical ventilation and/or all-cause mortality indicated clinical benefits, with some evidence against our model hypothesis of no significant effect at the current sample size (pooled hazard ratio = 0.62; 95% CI 0.42-0.91, n = 749).
CONCLUSION: Despite no clear mortality benefits in hospitalized patients with COVID-19, tocilizumab appears to reduce the likelihood of progression to mechanical ventilation.
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Nice that the authors updated their lit search after the initial journal submission. Both UpToDate and JHMI suggest tocilizumab if a patient is enrolled in a trial.
Although the topic studied is interesting and controversial (tocilizumab in COVID-19), this meta-analysis is methodologically flawed (limited reporting, incomplete publication of analyses, lack of GRADE to assess quality/certainty of individual outcomes) and will soon be outdated. There are better reviews on the topic already completed and soon to come out, especially once the RECOVERY trial provides a more definitive description of the impact of tocilizumab upon patient-important outcomes in COVID-19.
Awaiting further studies.
These data are accumulating daily. It's important for us to incorporate this into our hospital management of patients. Not sure if we should be drawing IL6 levels and deciding based on this result.
COVID-19 and its treatments continue to be of extreme importance to hospitalists. Finding a way to offset the inflammatory cascade for a minority of patients is clearly of great interest. Tocilizumab, an anti-IL6, should theoretically impact on this cascade; however, it could expose one to the risk for secondary infections. Therefore, studies that could measure overall mortality with this drug are sorely needed. In this systematic review, they identified 6 studies that randomized patients to tocilizumab. More than half of the weight of the trial was based on a single study with significant quality issues. They also attempted to measure a composite outcome that included mechanical ventilation. This is a difficult outcome to rely on, given that there is significant subjectivity by provider in it. Early on, we believed intubating everyone early was the right path; later, we avoided it. In the end, this study does not support tocilizumab outside of a trial setting.
Relatively small meta- analysis with less than robust data suggesting a lack of mortality benefit with use of tocilizumab for hospitalized patients with Covid-19. Might be less need for mechanical ventilation. Will require more study before this is standard of care.