P45 Mortality risk by exacerbation state in the ETHOS study

Abstract

<h3>Background</h3> Chronic obstructive pulmonary disease (COPD) exacerbations, especially severe exacerbations characterised by hospitalisation, cause patients’ health to worsen and can lead to the deterioration of existing comorbidities, and increased mortality. We assessed the time to death from progressive states of exacerbations using data from the recent Phase III ETHOS study (NCT02465567). <h3>Methods</h3> ETHOS evaluated the efficacy and safety of the inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β₂-agonist (ICS/LAMA/LABA) fixed-dose combination budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) 320/14.4/10μg and 160/14.4/10μg versus the LAMA/LABA glycopyrronium/formoterol fumarate dihydrate (GFF) MDI 14.4/10μg and the ICS/LABA budesonide/formoterol fumarate dihydrate (BFF) MDI 320/10μg, administered over 52 weeks as two actuations twice-daily via an Aerosphere^™ inhaler, in patients with a history of exacerbations in the prior year. In this post-hoc analysis, we present Kaplan-Meier curves for time to death (cumulative incidence) from time of entry to 4 progressive exacerbation states arising post-randomisation: i) no exacerbation, ii) 1 moderate exacerbation, iii) ≥2 moderate exacerbations, but no severe exacerbation and iv) ≥1 severe exacerbation. We evaluated the risk of dying during the time patients were in a specific state, censoring patients at the time of transition to another state or treatment discontinuation. Analysis, based on a time-dependent Cox model, was performed to estimate the hazard ratio of dying during the severe exacerbation state versus in the absence of a severe exacerbation. <h3>Results</h3> Risk of death was considerably higher after the occurrence of ≥1 severe exacerbation (figure 1); hazard ratio, 8.3 (95% CI, 5.6–12.3); however, it was noted that only 32% of patients who died suffered a previous severe exacerbation during the study. <h3>Conclusion</h3> The risk of dying after a severe exacerbation was higher than the risk before a severe exacerbation had occurred. Further research is needed to estimate the risk of patients transitioning from a moderate exacerbation state to a severe exacerbation state, and to understand whether there is a difference in the cause of death between patients who had a severe exacerbation versus those who had not. This analysis stresses the importance of appropriate clinical risk management, specifically for severe exacerbation prevention to lower the risk of mortality.