BACKGROUND: COVID-19 patients developing the acute respiratory distress syndrome (ARDS) show increased production of pro-inflammatory cytokines, including interleukin-6 (IL-6). The use of humanized monoclonal antibody against interleukin-6 receptor (IL-6R) may represent a potential treatment strategy. We analyzed the effects of compassionate use of tocilizumab and sarilumab on clinical outcome of patients affected by ARDS due COVID-19. METHODS: This single-center, observational, exploratory study was performed during the acute phase of COVID-19 outbreak, between March 7th and April 21st, 2020 in a University Hospital in Rome, Italy. All consecutive adult patients admitted to the intensive care unit with laboratory-confirmed COVID-19 and fulfilling ARDS criteria were enrolled. Patients who were treated with anti-IL-6R therapy were compared to those who were not, as per clinical decision. Inverse probability weights were applied to weight individual s contribution to survival curves and in the multivariate regression model. RESULTS : Among 105 ARDS patients, 65 received compassionate treatment with anti-IL-6R therapy (43 [66%] Tocilizumab [Hoffmann-La Roche, Basel, Switzerland] and 22 [34%] Sarilumab, respectively], with oxygenation improvement. In the multivariable Cox proportional regression hazards model with propensity score inverse probability weighting, patients who received anti-IL-6R treatment had lower risk of death compared to those who did not, with a hazard ration of 0.34 [95% confidence interval 0.17-0.74], P=0.001. CONCLUSIONS: Our data suggested that immune modulator therapy based on anti-human IL-6 receptor monoclonal antibodies might lead to improved outcome in patients with ARDS due to COVID-19. These data support the need for confirmatory randomized trials to assess the effect of immune modulator therapies on mortality.

Montini, L., De Pascale, G., Bello, G., L Grieco, D., Grasselli, G., Pesenti, A., M Ranieri, V., Cecconi, M., D'arcangelo, E., Gremese, E., Gemelli-icu Study Group, M. A., Compassionate use of anti-IL6 receptor antibodies in critically ill patients with acute respiratory distress syndrome due to SARS-CoV-2, <<MINERVA ANESTESIOLOGICA>>, 2021; 87 (10): 1080-1090. [doi:10.23736/S0375-9393.21.15609-3]

Compassionate use of anti-IL6 receptor antibodies in critically ill patients with acute respiratory distress syndrome due to SARS-CoV-2

Montini, Luca;De Pascale, Gennaro;Bello, Giuseppe;Cecconi, Maurizio;Gremese, Elisa;
2021

Abstract

BACKGROUND: COVID-19 patients developing the acute respiratory distress syndrome (ARDS) show increased production of pro-inflammatory cytokines, including interleukin-6 (IL-6). The use of humanized monoclonal antibody against interleukin-6 receptor (IL-6R) may represent a potential treatment strategy. We analyzed the effects of compassionate use of tocilizumab and sarilumab on clinical outcome of patients affected by ARDS due COVID-19. METHODS: This single-center, observational, exploratory study was performed during the acute phase of COVID-19 outbreak, between March 7th and April 21st, 2020 in a University Hospital in Rome, Italy. All consecutive adult patients admitted to the intensive care unit with laboratory-confirmed COVID-19 and fulfilling ARDS criteria were enrolled. Patients who were treated with anti-IL-6R therapy were compared to those who were not, as per clinical decision. Inverse probability weights were applied to weight individual s contribution to survival curves and in the multivariate regression model. RESULTS : Among 105 ARDS patients, 65 received compassionate treatment with anti-IL-6R therapy (43 [66%] Tocilizumab [Hoffmann-La Roche, Basel, Switzerland] and 22 [34%] Sarilumab, respectively], with oxygenation improvement. In the multivariable Cox proportional regression hazards model with propensity score inverse probability weighting, patients who received anti-IL-6R treatment had lower risk of death compared to those who did not, with a hazard ration of 0.34 [95% confidence interval 0.17-0.74], P=0.001. CONCLUSIONS: Our data suggested that immune modulator therapy based on anti-human IL-6 receptor monoclonal antibodies might lead to improved outcome in patients with ARDS due to COVID-19. These data support the need for confirmatory randomized trials to assess the effect of immune modulator therapies on mortality.
Inglese
Montini, L., De Pascale, G., Bello, G., L Grieco, D., Grasselli, G., Pesenti, A., M Ranieri, V., Cecconi, M., D'arcangelo, E., Gremese, E., Gemelli-icu Study Group, M. A., Compassionate use of anti-IL6 receptor antibodies in critically ill patients with acute respiratory distress syndrome due to SARS-CoV-2, <<MINERVA ANESTESIOLOGICA>>, 2021; 87 (10): 1080-1090. [doi:10.23736/S0375-9393.21.15609-3]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/215067
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