tetano
Editor, Senior Moderator
Infect Dis Ther
. 2020 Dec 6.
doi: 10.1007/s40121-020-00373-8. Online ahead of print.
Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection: A Spanish, Multicenter, Cohort Study
Bel?n Ruiz-Antor?n[SUP] 1 [/SUP], Ar?nzazu Sancho-L?pez[SUP] 2 [/SUP], Ferr?n Torres[SUP] 3 4 [/SUP], V?ctor Moreno-Torres[SUP] 5 [/SUP], Itziar de Pablo-L?pez[SUP] 6 [/SUP], Paulina Garc?a-L?pez[SUP] 7 [/SUP], Francisco Abad-Santos[SUP] 8 [/SUP], Clara M Rosso-Fern?ndez[SUP] 9 [/SUP], Ana Aldea-Perona[SUP] 10 [/SUP], Eva Montan?[SUP] 11 12 [/SUP], Ruth M Aparicio-Hern?ndez[SUP] 13 [/SUP], Roser Llop-Rius[SUP] 14 [/SUP], Consuelo Pedr?s[SUP] 15 [/SUP], Paloma Gij?n[SUP] 16 [/SUP], Carolina Hern?ndez-Carballo[SUP] 17 [/SUP], Mar?a J Pedrosa-Mart?nez[SUP] 18 [/SUP], Consuelo Rodr?guez-Jim?nez[SUP] 19 20 [/SUP], Guillermo Prada-Ramallal[SUP] 21 [/SUP], Lourdes Cabrera-Garc?a[SUP] 22 [/SUP], Josefa A Aguilar-Garc?a[SUP] 23 [/SUP], Roc?o Sanjuan-Jimenez[SUP] 24 25 [/SUP], Evelyn I Ortiz-Barraza[SUP] 26 [/SUP], Enrique S?nchez-Chica[SUP] 5 [/SUP], Ana Fern?ndez-Cruz[SUP] 27 [/SUP], TOCICOV-study group
Collaborators, Affiliations
Abstract
Background: We aimed to determine the impact of tocilizumab use on severe COVID-19 (coronavirus disease 19) pneumonia mortality.
Methods: We performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by inverse probability of the treatment weights (IPTW). Tocilizumab's effect in patients receiving steroids during the 48 h following inclusion was analysed.
Results: During the study period, 506 patients with severe COVID-19 fulfilled the inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days [interquartile range (IQR) 8-14]. Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls: 16.8% versus 31.5%, hazard ratio (HR) 0.514 [95% confidence interval (95% CI) 0.355-0.744], p < 0.001; weighted HR 0.741 (95% CI 0.619-0.887), p = 0.001. Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment [relative risk reduction (RRR) 46.7%]. We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in those treated with tocilizumab than in those treated with steroids alone [10.9% versus 40.2%, HR 0.511 (95% CI 0.352-0.741), p = 0.036; weighted HR 0.6 (95% CI 0.449-0.804), p < 0.001] (interaction p = 0.094).
Conclusions: These results show that survival of patients with severe COVID-19 is higher in those treated with tocilizumab than in those not treated and that tocilizumab's effect adds to that of steroids administered to non-intubated patients with COVID-19 during the first 48 h of presenting with respiratory failure despite oxygen therapy. Randomised controlled studies are needed to confirm these results.
Trial registration: European Union electronic Register of Post-Authorization Studies (EU PAS Register) identifier, EUPAS34415.
Keywords: COVID-19; Mortality; SARS-CoV-2; Steroids; Tocilizumab.
. 2020 Dec 6.
doi: 10.1007/s40121-020-00373-8. Online ahead of print.
Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection: A Spanish, Multicenter, Cohort Study
Bel?n Ruiz-Antor?n[SUP] 1 [/SUP], Ar?nzazu Sancho-L?pez[SUP] 2 [/SUP], Ferr?n Torres[SUP] 3 4 [/SUP], V?ctor Moreno-Torres[SUP] 5 [/SUP], Itziar de Pablo-L?pez[SUP] 6 [/SUP], Paulina Garc?a-L?pez[SUP] 7 [/SUP], Francisco Abad-Santos[SUP] 8 [/SUP], Clara M Rosso-Fern?ndez[SUP] 9 [/SUP], Ana Aldea-Perona[SUP] 10 [/SUP], Eva Montan?[SUP] 11 12 [/SUP], Ruth M Aparicio-Hern?ndez[SUP] 13 [/SUP], Roser Llop-Rius[SUP] 14 [/SUP], Consuelo Pedr?s[SUP] 15 [/SUP], Paloma Gij?n[SUP] 16 [/SUP], Carolina Hern?ndez-Carballo[SUP] 17 [/SUP], Mar?a J Pedrosa-Mart?nez[SUP] 18 [/SUP], Consuelo Rodr?guez-Jim?nez[SUP] 19 20 [/SUP], Guillermo Prada-Ramallal[SUP] 21 [/SUP], Lourdes Cabrera-Garc?a[SUP] 22 [/SUP], Josefa A Aguilar-Garc?a[SUP] 23 [/SUP], Roc?o Sanjuan-Jimenez[SUP] 24 25 [/SUP], Evelyn I Ortiz-Barraza[SUP] 26 [/SUP], Enrique S?nchez-Chica[SUP] 5 [/SUP], Ana Fern?ndez-Cruz[SUP] 27 [/SUP], TOCICOV-study group
Collaborators, Affiliations
- PMID: 33280066
- DOI: 10.1007/s40121-020-00373-8
Abstract
Background: We aimed to determine the impact of tocilizumab use on severe COVID-19 (coronavirus disease 19) pneumonia mortality.
Methods: We performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by inverse probability of the treatment weights (IPTW). Tocilizumab's effect in patients receiving steroids during the 48 h following inclusion was analysed.
Results: During the study period, 506 patients with severe COVID-19 fulfilled the inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days [interquartile range (IQR) 8-14]. Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls: 16.8% versus 31.5%, hazard ratio (HR) 0.514 [95% confidence interval (95% CI) 0.355-0.744], p < 0.001; weighted HR 0.741 (95% CI 0.619-0.887), p = 0.001. Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment [relative risk reduction (RRR) 46.7%]. We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in those treated with tocilizumab than in those treated with steroids alone [10.9% versus 40.2%, HR 0.511 (95% CI 0.352-0.741), p = 0.036; weighted HR 0.6 (95% CI 0.449-0.804), p < 0.001] (interaction p = 0.094).
Conclusions: These results show that survival of patients with severe COVID-19 is higher in those treated with tocilizumab than in those not treated and that tocilizumab's effect adds to that of steroids administered to non-intubated patients with COVID-19 during the first 48 h of presenting with respiratory failure despite oxygen therapy. Randomised controlled studies are needed to confirm these results.
Trial registration: European Union electronic Register of Post-Authorization Studies (EU PAS Register) identifier, EUPAS34415.
Keywords: COVID-19; Mortality; SARS-CoV-2; Steroids; Tocilizumab.