Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial
Background: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneu- monia the most frequent cause of death in COVID-19 patients.
Methods: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accom- plished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multi- variable logistic regression model to assess prognostic variables on survival.
Results: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regres- sion analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respira- tory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.
Conclusions: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxic- ity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.