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; Grieco, Domenico L; Grasselli, Giacomo; Pesenti, Antonio; Ranieri, Vito M; Cecconi, Maurizio; D'Arcangelo, Enzo; Gremese, Elisa; Antonelli, Massimo

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 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 suggest 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.