(A-075) Comparative effectiveness and safety of fixed-dose combination inhaled triple therapies in patients with chronic obstructive pulmonary disease: a population-based cohort study

Background: International guidelines recommend inhaled triple therapies of long-acting β2 agonists, long-acting muscarinic antagonists, and inhaled corticosteroids for patients with chronic obstructive pulmonary disease (COPD) who are at a higher risk of exacerbations or have suboptimal response to mono or dual maintenance therapies. There has been increasing use of triple therapies with fixed-dose combination (FDC) dosage. However, real-world evidence comparing different types of FDC triple therapies remain limited.

Objectives: This cohort study compared clinical outcomes of fluticasone-based and beclomethasone-based FDC triple therapies in patients with COPD and addressed a potential impact from medication adherence.

Methods: We identified patients with COPD who initiated fluticasone-based (vilanterol/umeclidinium/fluticasone once daily via a dry powder inhaler) or beclomethasone-based (formoterol/glycopyrronium/beclomethasone twice daily via a metered dose inhaler) FDC triple therapies from a nationwide Taiwanese database between 2019 and 2022. The study outcome included severe exacerbations, pneumonia, and cardiovascular events within one year of follow-up. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of individual outcomes comparing fluticasone-based versus beclomethasone-based FDC triple therapies after variable-ratio high dimensional propensity score (hd-PS) matching.

Results: A total of 12,600 patients were included in the hd-PS matched cohort (8,888 fluticasone-based FDC initiators, 3,712 beclomethasone-based FDC initiators). The HR comparing fluticasone-based FDC versus beclomethasone-based FDC was 0.79 (95% CI, 0.68-0.92) for exacerbations, 0.78 (0.64-0.94) for pneumonia, and 0.93 (0.66-1.32) for cardiovascular events. However, among patients who adhered to medications after treatment initiation (n=8,953; 6,439 fluticasone-based FDC adherents, 2,514 beclomethasone-based FDC adherents), both treatments showed similar effectiveness and safety profiles (HR of 1.00 [0.78-1.26] for exacerbations, 0.89 [0.68-1.16] for pneumonia, and 0.96 [0.59-1.56) for cardiovascular events]. The results did not change materially in several pre-specified sensitivity analyses.

Conclusions: This population-based cohort study found that fluticasone-based and beclomethasone-based FDC triple therapies may have comparable effectiveness and safety when patients adhere to their treatments.