The Effect of Patient Sex on Treatment Outcomes in COPD: A Post Hoc Analysis of the IMPACT Trial.

Introduction: Lung physiology and chronic obstructive pulmonary disease (COPD) pathophysiology differ between sexes. This post hoc analysis investigated the InforMing the Pathway of COPD Treatment (IMPACT) trial outcomes by patient sex.

Methods: IMPACT was a double-blind, 52-week trial. Patients ≥40 years with symptomatic COPD and a history of exacerbations were randomized 2:2:1 to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25μg, FF/VI 100/25μg, or UMEC/VI 62.5/25μg. Annual rate and risk of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 second (FEV) and St George's Respiratory Questionnaire (SGRQ) score, and safety were assessed.

Results: Of 10,355 patients, 66.3% were male. More females reported ≥2 moderate/severe prior exacerbations (58% versus 53%) at screening versus males. Additionally, females had worse mean (standard deviation) SGRQ scores (52.4[15.97] versus 49.8[17.24]) at baseline. FF/UMEC/VI improved annual exacerbation rate, lung function, and health status for both sexes versus dual therapy. The difference in trough FEV across time points with FF/UMEC/VI versus FF/VI was 103mL-110mL in males and 70mL-84mL in females. On-treatment moderate/severe exacerbation rates remained higher for females (FF/UMEC/VI: 0.99; FF/VI: 1.19; UMEC/VI: 1.35) than males (0.87; 1.01; 1.14). Fewer exacerbations were experienced by females with eosinophil counts <150 cells/µL (0.81[0.68, 0.97], =0.024) or <2 exacerbations in the past year (0.73[0.57, 0.94], =0.013) with FF/UMEC/VI versus UMEC/VI.

Conclusion: More females with COPD reported exacerbations in the prior year at screening, as well as during the study, versus males, across all treatments. FF/UMEC/VI improved exacerbation rates versus UMEC/VI in females with eosinophil counts <150 cells/µL or <2 exacerbations in the prior year, suggesting inhaled corticosteroids may play an important role in exacerbation reduction for females in this patient population. Clinical Trial Registration: GSK (CTT116855/NCT021645B).