Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19

Abstract

Background: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment.

Methods: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW).

Results: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia.

Conclusions: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.

Keywords: COVID-19; SARS-CoV-2; interleukin-6; tocilizumab.

Figure 1.

Study cohort flow chart. Abbreviations: COVID-19, coronavirus disease 2019; IPTW, inverse probability of treatment weighting; MI, multiple imputation; RCT, randomized controlled trial; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Kaplan-Meier estimates for probability of survival as a function of time since mechanical ventilation onset, stratified by tocilizumab treatment (n = 154; n = 46 deaths).

Figure 3.

Patient status post–ventilator onset on a 6-level ordinal scale integrating superinfection occurrence, stratified by tocilizumab treatment. A, The distribution of patient status, by number of days after onset of mechanical ventilation through day 28 of follow-up. B, Individual patient trajectories on the 6-level ordinal scale over the study period. Each row represents changes in individual patient status from time of onset of mechanical ventilation until event (death) or end of the study period (19 May 2020). Horizontal lines correspond to elapsed time, with colors corresponding to clinical status of the patient. Solid circles represent death, and hollow circles represent discharge from hospital (alive). The middle panel indicates the most recent patient status. Gray vertical lines mark 28-day follow-up. Abbreviation: MV, mechanical ventilation.