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

Introduction: Lung physiology and COPD pathophysiology differ between sexes. This post hoc analysis investigated IMPACT trial outcomes by patient sex.

Methods: IMPACT was a double-blind, 52-week trial. Patients ≥40 years with symptomatic COPD and history of exacerbations were randomised 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 FEV₁ and SGRQ score, and safety were assessed.

Results: Of 10,355 patients, 66.3% were male. More females reported ≥2 moderate/severe prior exacerbations (58% vs 53%) at screening versus males. Additionally, females had worse mean (SD) SGRQ scores (52.4[15.97] vs 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 FEV₁ across time points with FF/UMEC/VI versus FF/VI was 103-110mL in males and 70-84mL 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). Females experienced fewer exacerbations with eosinophil counts <150 cells/µL (0.81[0.68,0.97], p=0.024) or <2 exacerbations in the past year (0.73[0.57,0.94],p=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/NCT02164513).