Effects of tocilizumab on mortality in hospitalized patients with COVID-19: A multicenter cohort study

Martínez-Sanz, Javier; Muriel, Alfonso; Ron, Raquel; Herrera, Sabina; Pérez-Molina, José A.; Moreno, Santiago; Serrano-Villar, Sergio

OBJECTIVES: Tocilizumab has been proposed as a candidate therapy for patients with severe coronavirus disease 2019 (COVID-19), especially among those with higher systemic inflammation. Here, we investigate the association between tocilizumab use and mortality in a large cohort of hospitalized patients. METHODS: Cohort study of patients hospitalized with COVID-19 in Spain. The primary outcome was time to death and the secondary outcome time to intensive care unit admission (ICU) or death. We used inverse-probability weighting to fit marginal structural models adjusted for time-varying covariates to determine the causal relationship between tocilizumab use and the outcomes. RESULTS: A total of 1,229 patients were analyzed, with 261 patients (61 deaths) in the tocilizumab group and 969 patients (120 deaths) in the control group. In the adjusted marginal structural models, a significant interaction between tocilizumab use and high C-reactive protein (CRP) levels was detected. Tocilizumab was associated with decreased risk of death (aHR 0.34, 95% CI 0.16–0.72, p=0.005) and ICU admission or death (aHR 0.38, 95% CI 0.19–0.81, p=0.011) among patients with baseline CRP >150 mg/L, but not among those with CRP ≤150 mg/L. Exploratory subgroup analyses yielded point estimates that were consistent with these findings. CONCLUSIONS: In this large observational study, tocilizumab was associated with a lower risk of death or ICU or death in patients with higher CRP levels. While the results of ongoing clinical trials of tocilizumab in patients with COVID-19 will be important to establish its safety and efficacy, our findings have implications for the design of future clinical trials.