Tocilizumab Effectiveness in Mechanically Ventilated COVID-19 Patients: A Multicenter Retrospective Study Using Propensity Score-Based Methods

ABSTRACT

Introduction: The use of the interleukin-6 blocker tocilizumab in critically-ill mechanically ventilated patients with coronavirus disease 2019 (COVID-19) is less well studied. Research Question or Hypothesis: Is tocilizumab effective in mechanically ventilated COVID-19 patients. Study Design: A multicenter retrospective study conducted in six Saudi Arabian hospitals. Methods: Patients admitted between March 2020 to January 2021 were screened. Confirmed COVID-19 mechanically ventilated adult patients (≥18 years old) were included. Mortality after mechanical ventilation was the primary outcome and rate of extubation rate was the secondary outcome. To achieve balance in the data, we implemented inverse propensity score weighting (IPSW) and propensity score matching (PSM). In addition to performing survival analysis on the primary outcome, Cox proportional modeling with time dependency covariance was used to account for immortal bias. For the secondary outcome, competing risk analysis was implemented with death while intubated being the competing risk. Results: A total of 889 patients were screened and 456 patients were eligible for inclusion (tocilizumab, n=193, control, n= 263). The mean age (±SD) for tocilizumab arm was 59.3(±14.2) and 58.5(±13.7) years for the control arm. Adequate balance in covariates of interest was achieved in the IPSW and PSM analyses. In the IPSW analysis, tocilizumab was associated with lower mortality (HR=0.37, 95%CI=0.55-0.69) but not in the PSM analysis with (HR=0.80, 95%CI=0.57-1.12). After accounting for immortal time bias both the IPSW (HR=0.82, 95%CI=0.62-1.10) and the PSM (HR=0.86, 95%CI=0.64-1.16,) analyses showed no difference in overall mortality. Conversely, tocilizumab was associated with a higher rate of extubation (33.6%) versus the control arm (11.9%) with subdistributional hazards (SHR= 3.1, 95%CI=1.86-5.16). Conclusion: Tocilizumab was not effective in reducing mortality in mechanically ventilated COVID-19 patients. However, a higher extubation rate was observed. A large randomized controlled trial in this population is needed.