The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study.

• Main Authors: Jovana Milic, Federico Banchelli, Marianna Meschiari, Erica Franceschini, Giacomo Ciusa, Licia Gozzi, Sara Volpi, Matteo Faltoni, Giacomo Franceschi, Vittorio Iadisernia, Dina Yaacoub, Giovanni Dolci, Erica Bacca, Carlotta Rogati, Marco Tutone, Giulia Burastero, Alessandro Raimondi, Marianna Menozzi, Gianluca Cuomo, Luca Corradi, Gabriella Orlando, Antonella Santoro, Margherita Digaetano, Cinzia Puzzolante, Federica Carli, Andrea Bedini, Stefano Busani, Massimo Girardis, Andrea Cossarizza, Rossella Miglio, Cristina Mussini, Giovanni Guaraldi, Roberto D'Amico
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2021-01-01
• Series: PLoS ONE
• Online Access: https://doi.org/10.1371/journal.pone.0251378

<h4>Background</h4>The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery.<h4>Methods</h4>In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery.<h4>Results</h4>Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2-5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1-0.7) or in OT (HR = 0.1, 95% CI = 0.0-0.8) treated with tocilizumab.<h4>Conclusion</h4>To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.