Effects of Tocilizumab on Mortality in Hospitalized Patients with COVID-19: A Multicenter Cohort Study

Martinez-Sanz, J.; Muriel, A.; Ron, R.; Herrera, S.; Perez-Molina, J. A.; Moreno, S.; Serrano-Villar, S.

Background While there are no treatments with proven efficacy for patients with severe coronavirus disease 2019 (COVID 19), tocilizumab has been proposed as a candidate therapy, especially among patients with higher systemic inflammation. Methods We conducted a 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 and 10,673 person/days were analyzed. 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 to 0.72, p=0.005) and ICU admission or death (aHR 0.38, 95% CI 0.19 to 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 and support the use of tocilizumab among subjects with higher CRP levels.