@article{discovery10130588,
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
          volume = {47},
           pages = {641--652},
           month = {June},
          number = {6},
         journal = {Intensive Care Medicine},
       publisher = {SPRINGER},
            year = {2021},
           title = {Tocilizumab in COVID-19: a meta-analysis, trial sequential analysis, and meta-regression of randomized-controlled trials},
        keywords = {COVID-19, 
Immunologic factors, 
Interleukin-6, 
Meta-analysis,},
             url = {https://doi.org/10.1007/s00134-021-06416-z},
          author = {Snow, TAC and Saleem, N and Ambler, G and Nastouli, E and Singer, M and Arulkumaran, N},
        abstract = {PURPOSE: 
Interleukin-6 (IL-6) levels discriminate between patients with mild and severe COVID-19, making IL-6 inhibition an attractive therapeutic strategy. We conducted a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of randomized-controlled trials to ascertain the benefit of IL-6 blockade with tocilizumab for COVID-19.

METHODS:

We included randomized-controlled trials (RCTs) allocating patients with COVID-19 to tocilizumab. Our control group included standard care or placebo. Trials co-administering other pharmacological interventions for COVID-19 were not excluded. Primary outcome was 28-30 day mortality. Secondary outcomes included progression-to-severe disease defined as need for mechanical ventilation, intensive-care unit (ICU) admission, or a composite.

RESULTS: We identified 10 RCTs using tocilizumab, 9 of which reported primary outcome data (mortality), recruiting 6493 patients with 3358 (52.2\%) allocated to tocilizumab. Tocilizumab may be associated with an improvement in mortality (24.4\% vs. 29.0\%; OR 0.87 [0.74-1.01]; p = 0.07; I2 = 10\%; TSA adjusted CI 0.66-1.14). Meta-regression suggested a relationship between treatment effect and mortality risk, with benefit at higher levels of risk (logOR vs \%risk beta = ?0.018 [?0.037 to ?0.002]; p = 0.07). Tocilizumab did reduce the need for mechanical ventilation and was associated with a benefit in the composite secondary outcome but did not reduce ICU admission.

CONCLUSIONS:
For hospitalized COVID-19 patients, there is some evidence that tocilizumab use may be associated with a short-term mortality benefit, but further high-quality data are required. Its benefits may also lie in reducing the need for mechanical ventilation.}
}