Combined treatment with formoterol and tiotropium is more efficacious than treatment with tiotropium alone in patients with chronic obstructive pulmonary disease, regardless of smoking status, inhaled corticosteroid use, baseline severity, or gender

Abstract

A recent randomized, double-blind, parallel-group, active-controlled, multicenter study of 255 patients ≥ 40 years of age with chronic obstructive pulmonary disease (COPD) showed that combined formoterol (FOR) and tiotropium (TIO) treatment in patients with COPD significantly improved lung function as well as symptoms and other patient-reported outcomes compared with TIO alone. FOR and TIO are long-acting bronchodilators that represent the β₂-adrenergic agonist and anticholinergic classes, respectively. However, the possible influence of smoking status, inhaled corticosteroid (ICS) use, baseline disease severity, and gender differences on bronchodilator efficacy requires further investigation. Using data from the previously published study mentioned above, a post hoc analysis was performed to examine the efficacy of combined FOR + TIO treatment compared with TIO monotherapy in subgroup analyses of men and women, current and ex-smokers, ICS users and non-ICS users, and patients with moderate and severe/very severe COPD. Efficacy comparisons were based on the changes in forced expiratory volume in 1 s measured 0-4 h after the morning dose (FEV₁ AUC₀₋₄h). After a run-in period, patients were treated for 12 weeks with either FOR 12 μg twice daily (BID) plus TIO 18 μg once daily (QD) in the morning (AM, n = 124) or with FOR placebo BID plus TIO 18 μg QD AM (n = 131). The least squares mean change from baseline in the normalized FEV₁ AUC₀₋₄h was assessed using analysis of covariance. With the exception of treatment differences at week 4 in smokers and subjects with "very severe" COPD, and at weeks 4, 8, and 12 for ICS users and non-ICS users (p values not determined), FOR + TIO was significantly superior (P < 0.05) to TIO alone at all time points (weeks 4, 8, 12, and endpoint), regardless of gender, smoking status, ICS use, or COPD severity. We conclude that coadministered FOR + TIO significantly improves lung function compared with TIO treatment alone in COPD patients regardless of differences in patient subgroups.