Comparative Effectiveness and Safety of Fluticasone-Umeclidinium-Vilanterol and Beclomethasone-Glycopyrronium-Formoterol Single-Inhaler Triple Therapies for COPD: Real-World Observational Study

Purpose: Multiple guidelines recommend single-inhaler triple therapy (SITT) for some patients with COPD. The first two SITTs approved for COPD were beclomethasone-glycopyrronium-formoterol (BEGF, twice daily) and fluticasone-umeclidinium-vilanterol (FUV, once daily). No study has compared the effectiveness and safety of these SITTs on major outcomes. Patients and Methods: We identified a cohort of patients with COPD, 40 years of age or older, from the United Kingdom’s Clinical Practice Research Datalink. The patients who initiated treatment with FUV or BEGF were compared on the incidence of moderate or severe COPD exacerbations, and of pneumonia, over one year, after balancing baseline characteristics by propensity score weighting. Results: The study cohort included 34,825 initiators of FUV and 39,288 initiators of BEGF, well balanced after weighing. The adjusted hazard ratio (HR) of a first moderate or severe exacerbation with FUV compared with BEGF was 0.91 (95% CI: 0.89– 0.93), while for severe exacerbation it was 0.92 (95% CI: 0.86– 0.97), corresponding to 27.9 fewer subjects with a moderate or severe exacerbation and 1.0 fewer with a severe exacerbation per 100 treated with FUV for one year. The HR of pneumonia requiring hospitalisation, comparing FUV with BEGF, was 1.06 (95% CI 0.99– 1.13), over all patients. It was 1.14 (95% CI 1.06– 1.24) among those classified as GOLD Group E, and 1.10 (95% CI 1.02– 1.19) among those with a blood eosinophil count ≤ 300 cells/μL, corresponding to increases of 1.7 and 1.0 more subjects with a severe pneumonia per 100 treated with FUV for one year, respectively. Conclusion: In a real-world clinical practice setting of COPD treatment, initiating triple therapy with FUV was associated with a lower incidence of moderate and severe exacerbations than with BEGF. On the other hand, the incidence of a severe pneumonia requiring hospitalisation was higher with FUV among GOLD Group E subjects or those whose blood eosinophil count is not elevated. Keywords: cohort studies, COPD exacerbations, new-user design, observational study, pneumonia