Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19

Importance Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. Objective To test whether tocilizumab decreases mortality in this population. Design, Setting, and Participants The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. Exposures Treatment with tocilizumab in the first 2 days of ICU admission. Main Outcomes and Measures Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Results Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). Conclusions and Relevance Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed. Question Is early treatment with tocilizumab associated with a lower mortality rate among critically ill patients with coronavirus disease 2019 (COVID-19)? Findings In this multicenter cohort study that included 3924 patients, the risk of in-hospital death was estimated to be lower with tocilizumab treatment in the first 2 days of intensive care unit admission compared with no early use of tocilizumab. Meaning These findings suggest that among critically ill patients with COVID-19, early treatment with tocilizumab may reduce mortality, although the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed. This cohort study assesses mortality rates among patients with COVID-19 admitted to intensive care who were treated with tocilizumab.

Automated summary

A multicenter cohort study found that early treatment with tocilizumab may reduce mortality among critically ill patients with COVID-19. Further research from randomized clinical trials is needed to confirm these findings.