Patients with chronic obstructive pulmonary disease (COPD) and an exacerbation history whose blood eosinophil counts are at least 100 cells/mm3 stand to benefit from the use of triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) 320/14.4/10 more than dual therapy, according to study results published in the International Journal of Chronic Obstructive Pulmonary Disease.
Researchers conducted a subgroup post hoc analysis of data from the ETHOS trial (ClinicalTrials.gov identifier: NCT02465567) to evaluate how baseline blood eosinophil (EOS) counts affected the treatment benefits of BGF triple therapy over dual therapy (ie, either glycopyrronium/formoterol fumarate dihydrate [GFF] or budesonide/formoterol fumarate dihydrate [BFF]) in patients who had experienced moderate to severe COPD exacerbations.
In the ETHOS trial, patients 40 to 80 years of age with a history of COPD were randomly assigned in a 1:1:1:1 ratio to 1 of the following 4 treatment groups: (1) BGF 320/14.4/10 μg; (2) BGF 160/14.4/10 μg; (3) GFF 14.4/10 μg; or (4) BFF 320/10 μg, via a metered-dose inhaler. For the current post hoc analysis, researchers evaluated endpoints according to baseline EOS counts with the use of Global Initiative for Obstructive Lung Disease (GOLD) thresholds (ie, <100 cells/mm3, ≥100 cells/mm3, ≥100 to <300 cells/mm3, and ≥300 cells/mm3). Continuous relationships between treatment effects and EOS counts on exacerbations, lung function, symptoms, disease-related quality of life (QoL), and safety were examined as well.
A total of 8509 patients (59.7% male) were enrolled in the modified intention-to-treat (mITT) population. The mean (SD) patient age was 64.7 (7.6) years. Among individuals in the mITT population, 17.3% of patients had an EOS count of <100 cells/mm3; 82.6% had an EOS count of ≥100 cells/mm3; 67.9% had an EOS count of ≥100 to <300 cells/mm3; and 14.7% had an EOS count of ≥300 cells/mm3. Additionally, within the 52-week study period, 40% of participants had both a minimum EOS count of <100 cells/mm3 and a maximum EOS count of ≥100 cells/mm3. Further, 5.9% of participants had a minimum EOS count of <100 cells/mm3 and a maximum EOS count of >300 cells/mm3.
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Overall, these findings confirm those of previous studies, that patients with EOS counts ≥300 cells/mm3 experience the greatest benefits of ICS-containing triple therapy on exacerbation rates, symptoms, disease-related QoL, and lung function.
Study results showed that a higher proportion of participants who received GFF had a maximum EOS count of greater than 300 cells/mm3, compared with patients treated with BGF 320, BGF 160, and BFF (34.9% vs 30.1% vs 30.6% vs 28.9%, respectively). A smaller percentage of patients who received GFF had a maximum EOS count of less than 100 cells/mm3 , compared with patients treated with BGF 320, BGF 160, and BFF (3.8% vs 4.7% vs 4.9% vs 4.9%, respectively).
Treatment with BGF 320 instead of GFF improved outcomes across all subgroups for rescue medication use and lung function and also improved the St. George’s Respiratory Questionnaire total score, Transition Dyspnea Index focal score, and Exacerbations of Chronic Pulmonary Disease total score in all subgroups other than the subgroup of patients with EOS less than 100 cells/m3. The benefits of BGF 320 vs BFF were generally consistent across all patient subgroups. Safety data were comparable across the treatment arms.
Several limitations of the current analysis should be noted. Although the patient population was large (n=8509), the proportions of participants with baseline EOS counts of at least 300 cells/mm3 and less than 100 cells/m3 were relatively small (14.7% vs 17.3%, respectively). This was associated with greater uncertainty in the estimates used in these subgroups. In addition, ETHOS was neither designed nor prospectively powered to attain statistical significance in these post hoc subgroup analyses.
The authors concluded that “Overall, these findings confirm those of previous studies, that patients with EOS counts ≥300 cells/mm3 experience the greatest benefits of ICS-containing triple therapy on exacerbation rates, symptoms, disease-related QoL, and lung function.”
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
