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. 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.

Aims: Effect of tocilizumab on ventilator-free days among critically ill SARS-CoV-2 patients.

Method: Retrospective propensity score matching study, comparing mechanically ventilated patients who received tocilizumab to a control group.

Results: 29 patients in the intervention group were compared to 29 controls. Matched groups were similar. Ventilator-free days were more numerous in the intervention group (SHR 2.7, 95% CI: 1.2 - 6.3; p = 0.02), ICU mortality rate was not different (37.9% versus 62%, p = 0.1), actual ventilator-free periods were significantly longer in tocilizumab group (mean difference 4.7 days; p = 0.02). Sensitivity analysis showed a significantly lower hazard ratio of death in tocilizumab group (HR 0.49, 95% CI: 0.25 - 0.97; p = 0.04). There was no difference in positive cultures among groups (55.2% in tocilizumab group versus 34.5% in the control; 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 periods, and insignificantly lower mortality and higher superinfection.

Keywords: SARS-CoV-2; tocilizumab; ventilator-free days.

Figure 1

Patients’ and study groups’ flow diagram: Flow diagram of included and excluded patients in the study, and matched groups.

Figure 2

Kaplan Meier survival curve: Survival of patients in both groups up to 28 days, evaluated by Log – Rank test showing significant difference (p = 0.04).