Effects of tocilizumab on mortality in hospitalized patients with COVID-19: a multicentre cohort study

• DOI: 10.1016/j.cmi.2020.09.021
• Publication Date: 2020-09-23T14:10:59Z
• Authors: Javier Martínez-Sanz; Alfonso Muriel; Raquel Ron; Sabina Herrera; José A. Pérez-Molina; Santiago Moreno; Sergio Serrano-Vi...
• Keywords: Microbiology (medical); Aged, 80 and over; Male; SARS-CoV-2; COVID-19; General Medicine; Tocilizumab; Middle Aged; Antibodies, Monoclonal, Humanized; C-reactive protein; COVID-19 Drug Treatment; 3. Good health; Cohort Studies; Hospitalization; Intensive Care Units; Infectious Diseases; C-Reactive Protein; Treatment Outcome; Spain; Humans; Original Article; Female; Hospital Mortality; Mortality; Aged

ABSTRACTBackgroundWhile 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.MethodsWe 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.ResultsA 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 0.16–0.72, 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.ConclusionsIn 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.