Tocilizumab in COVID-19: a meta-analysis, trial sequential analysis, and meta-regression of randomized-controlled trials

Intensive Care Med. 2021 Jun;47(6):641-652. doi: 10.1007/s00134-021-06416-z. Epub 2021 May 21.


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.

Keywords: COVID-19; Immunologic factors; Interleukin-6; Meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • COVID-19 Drug Treatment*
  • Humans
  • Randomized Controlled Trials as Topic
  • Respiration, Artificial
  • SARS-CoV-2


  • Antibodies, Monoclonal, Humanized
  • tocilizumab