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

Abstract

Mona Bafadhel,1 Klaus F Rabe,2 Fernando J Martinez,3 Dave Singh,4 Patrick Darken,5 Martin Jenkins,6 Magnus Aurivillius,7 Mehul Patel,6 Paul Dorinsky8 1Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 2LungenClinic Grosshansdorf and Christian-Albrechts University Kiel, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 3Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, USA; 4Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Hospitals Trust, Manchester, UK; 5AstraZeneca, Gaithersburg, MD, USA; 6AstraZeneca, Cambridge, UK; 7AstraZeneca, Gothenburg, Sweden; 8Formerly of AstraZeneca, Durham, NC, USACorrespondence: Mona Bafadhel, Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, 5th floor, Tower Wing, Guy’s Hospital, Great Maze Pond, London SE1 9RT, UK, Tel [phone], Email [email protected]: 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/mm3), 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/mm3. 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.Graphical Abstract: Keywords: eosinophils, inhaled corticosteroids, triple therapy

Keywords

• eosinophils
• inhaled corticosteroids
• triple therapy