Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19

  • Emily C Somers
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Gregory A Eschenauer
    Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA
  • Jonathan P Troost
    Michigan Institute for Clinical & Health Research, University of Michigan, Ann Arbor, Michigan, USA
  • Jonathan L Golob
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Tejal N Gandhi
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Lu Wang
    Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA
  • Nina Zhou
    Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA
  • Lindsay A Petty
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Ji Hoon Baang
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Nicholas O Dillman
    Department of Pharmacy, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • David Frame
    Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA
  • Kevin S Gregg
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Dan R Kaul
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Jerod Nagel
    Department of Pharmacy, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Twisha S Patel
    Department of Pharmacy, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Shiwei Zhou
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Adam S Lauring
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • David A Hanauer
    Department of Learning Health Sciences, University of Michigan, Ann Arbor, Michigan, USA
  • Emily Martin
    Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA
  • Pratima Sharma
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Christopher M Fung
    Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • Jason M Pogue
    Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA

説明

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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 &lt; .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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.</jats:p> </jats:sec>

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