Benefits of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate on COPD Exacerbations, Lung Function, Symptoms, and Quality of Life Across Blood Eosinophil Ranges: A Post-Hoc Analysis of Data from ETHOS

PURPOSE: Blood eosinophil (EOS) count can guide treatment decisions for chronic obstructive pulmonary disease (COPD). In the 52-week ETHOS study (NCT02465567), budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) triple therapy at two inhaled corticosteroid doses reduced moderate/severe exacerbation rates and improved lung function, symptoms, and disease-related quality of life (QoL) versus dual therapy with glycopyrronium/formoterol fumarate dihydrate (GFF) or budesonide/formoterol fumarate dihydrate (BFF) in patients with moderate-to-very severe COPD. This subgroup analysis evaluated treatment benefits in ETHOS by baseline EOS count. METHODS: Patients (40-80 years) with a COPD history were randomly assigned 1:1:1:1 to receive BGF 320/14.4/10 µg, BGF 160/14.4/10 µg, GFF 14.4/10 µg, or BFF 320/10 µg via a metered-dose inhaler. This post-hoc analysis assessed endpoints by baseline EOS count using Global Initiative for Obstructive Lung Disease thresholds (<100, ≥100, ≥100-<300, ≥300 cells/mm(3)), and investigated continuous relationships between treatment effects and EOS count on exacerbations, symptoms, disease-related QoL, lung function, and safety. RESULTS: In the modified intention-to-treat population (n=8509), 82.6% had EOS counts ≥100 cells/mm(3). BGF 320 reduced moderate/severe exacerbation rates versus GFF in the ≥100, ≥100-<300, and ≥300 subgroups; treatment differences increased with EOS count. BGF 320 improved rescue medication use and lung-function outcomes across all subgroups, and St George's Respiratory Questionnaire total score, Transition Dyspnea Index focal score, and Exacerbations of Chronic Pulmonary Disease Tool total score in all except the <100 subgroup versus GFF. Benefits of BGF 320 versus BFF were generally consistent across subgroups. Safety data were comparable across subgroups. CONCLUSION: Benefits of BGF versus GFF were observed across EOS counts, particularly at ≥100 cells/mm³; versus BFF, benefits were largely independent of EOS. These findings confirm that benefits of ICS-containing triple therapy are not restricted to EOS counts ≥300 cells/mm³, supporting recommendations to consider triple therapy in patients with an exacerbation history and EOS counts ≥100 cells/mm³.

• Bafadhel, M.
• Rabe, K. F.
• Martinez, F. J.
• Singh, D.
• Darken, P.
• Jenkins, M.
• Aurivillius, M.
• Patel, M.
• Dorinsky, P.