Effect of Tocilizumab on “ventilator free days” composite outcome in SARS-CoV-2 patients. A retrospective competing risk analysis

Abstract

Background: SARS CoV 2 infection demonstrates a wide range of severity, the more severe cases demonstrate a cytokine storm with elevated serum interleukin 6, hence IL 6 receptor antibody Tocilizumab was tried for the management of severe cases. Objectives: The effect of Tocilizumab treatment on the composite outcome of ventilator free days, among critically ill SARS CoV 2 patients. Method: Retrospective observational propensity score matching study, comparing mechanically ventilated patients upon ICU admission who received Tocilizumab to a control group. Utilizing competing risk analysis method, and reporting subdistributional hazard ratio of a composite outcome of ventilator free days at day 28. Results: 29 patients in the intervention group were compared to 29 patients in the control group. Matched groups were similar at base line. The primary outcome of ventilator free days was higher in the intervention group (SHR 2.7, 95% CI: 1.2 to 6.3; p = 0.02), crude ICU mortality rate was not different between Tocilizumab and control groups (37.9% versus 62% respectively, p = 0.1), actual ventilator free days were significantly longer in Tocilizumab group (mean difference 4.7 days, 95% CI 1.1 to 8.3; p = 0.02). Sensitivity analysis by Cox regression showed a significantly lower hazard ratio of death in Tocilizumab group (HR 0.49, 95% CI: 0.25 to 0.97; p = 0.04). While there was no difference in grown positive cultures among groups (55.2% in Tocilizumab group versus 34.5% in the control, 95% CI of difference: -7.11% to 54.4%; p = 0.1). Conclusion: Tocilizumab may improve the composite outcome of ventilator free days at day 28 among mechanically ventilated SARS-CoV-2 patients, it is associated with significantly longer actual ventilator free days, and insignificantly lower mortality and superinfection.