Effect of tocilizumab in hospitalized patients with severe pneumonia COVID-19: a cohort study

  1. Benjamin Rossi
  2. Lee S. Nguyen
  3. Philippe Zimmermann
  4. Faiza Boucenna
  5. Louis Dubret
  6. Louise Baucher
  7. Helene Guillot
  8. Marie-Anne Bouldouyre
  9. Yves Allenbach
  10. Joe-Elie Salem
  11. Paul Barsoum
  12. Arezki Oufella
  13. Helene Gros
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Abstract

Background

Tocilizumab, a drug targeting interleukin-6 administrated in the right timeframe may be beneficial in coronavirus-disease-2019 (COVID-19). We aimed to assess its benefit, drawing from observations in compassionately treated patients.

Methods

In a retrospective case-control study, treatment effect (tocilizumab 400mg, single-dose) was assessed using three statistical methods: propensity-score matching, Cox multivariable survival and inverse probability score weighting (IPSW) analyses. Were included all patients hospitalized with COVID-19, who presented severity criteria with SpO2≤96% despite O2-support ≥6L/min for more than 6 hours. Were excluded patients in critical care medicine department and those under invasive mechanical ventilation. Primary outcome was a composite of mortality and ventilation, with a maximum follow-up of 28 days.

Results

246 patients were included (106 treated by tocilizumab). They were 67.6 ±15.3 years-old, with 95 (38.5%) women. Delay between first symptoms and inclusion was 8.4 ±4.5 days. Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-days follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes (hazard ratio (HR) = 0.49 (95% confidence interval (95CI) = 0.3–0.81), p-value = 0.005). These results were similar in the overall cohort (n = 246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR = 0.26 (95CI = 0.135–0.51, p = 0.0001), confirmed by IPSW analysis (p<0.0001). Analyses on mortality with 28-days follow-up yielded similar results.

Conclusion

In this retrospective study, tocilizumab single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.

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