Current best evidence for clinical care (more info)
The efficacy of tocilizumab (TOC), monoclonal antibody against interleukin-6 (IL-6) receptor, in patients with coronavirus disease-2019 (COVID-19) patients has led to conflicting results. We performed a systematic review and meta-analysis to compare the efficacy of addition of TOC to standard of care (SOC) versus SOC in patients with COVID-19. We performed a comprehensive literature search of PubMed, Embase, Web of Science, WHO COVID, LitCOVID, and Cochrane databases. Pooled outcomes (overall mortality, need for mechanical ventilation, intensive care unit admission, and secondary infections) were compared using DerSimonian-Laird/Random-effects approach. Risk difference (RD), confidence interval (CI), and p values were generated. A total of 23 studies with 6279 patients (1897 in TOC and 4382 in SOC group, respectively) were included. The overall mortality was lower in TOC group compared to SOC group (RD: -0.06; CI: -0.12 to -0.01; p = .03). Subgroup analysis including studies with only severe cases revealed lower mortality (RD: -0.12; CI: -0.18 to -0.06; p < .01) and need for mechanical ventilation (RD: -0.11; CI: -0.19 to -0.02; p = .01) in TOC group compared to SOC group. The addition of TOC to SOC has the potential to reduce mortality and need for mechanical ventilation in patients with severe COVID-19. Randomized controlled trials are needed to validate this.
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In this meta analysis of observational studies, the IL 6 inhibitor tocilizumab was compared to usual care. Confounding could not be controlled for and is a huge problem in this COVID world; they studied outcomes including death, ICU admission and mechanical ventilation. Of these, ICU admission mechanical ventilation were used very early on because this was thought to be of benefit and is done much less now, so this is a moving target; that this probably outcome that should be followed that matters. In their studies, the I squared was 89%, indicating ridiculous heterogeneity and likely suggests that the populations should not be combined. I do not think anyone should act on this information until we have clinical trials; I believe that this is still currently experimental. Many of the studies were lacking information on secondary infections which is an important question.
There is conflicting results with the previous metanalysis published in NEJM. This subgroup analysis provides a very low level of evidence.
This meta analysis confirms the widely held belief that Tocilizumab lowers mortality and need for ICU admission in patients with coronavirus infection, especially in those with severe disease.
This is a helpful summary. Unfortunately, the results are not robust as there are many small studies with a high risk of bias. Emerging results from clinical trials suggests that there is no clinical benefit.
This meta-analysis includes most of clinical studies that have evaluated tocilizumab in COVID-19 patients. Their results, besides the moderate-quality studies included in the analysis, suggest potential benefits of this drug in patients with severe COVID-19.
It would be nice to know if the decision to look at severe cases was an apriori decision. This can be helpful as an intensivist to determine the efficacy for IL-6 blockade.
There are different doses and there is no measurement of IL-6. The results must be taken with extreme caution due tot he differences in standard of care and, importantly, the lack of placebo-controlled trials.