Comparable spirometric efficacy of tiotropium compared with salmeterol plus fluticasone in patients with COPD: A pilot study

Abstract

Background International guidelines recommend the long-acting anticholinergic, tiotropium, or long-acting β 2-agonists as maintenance therapy in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). The efficacy of long-acting β 2-agonists combined with inhaled corticosteroids (ICS) in the treatment of COPD has also been confirmed for severe and very severe COPD, but data comparing tiotropium with the combination of a long-acting β 2-agonist and an ICS are lacking. Methods This 6-week multicentre, randomised, double-blind, triple-dummy pilot study compared the bronchodilator effects of tiotropium 18 μg once daily ( n=56) vs. the combination of salmeterol 50 μg plus fluticasone 250 μg twice daily ( n=51) in patients with moderate-to-very severe COPD. Serial spirometry was performed over 12 h after 6 weeks of treatment. The primary endpoint was forced expiratory volume in 1 s (FEV 1) area under the curve from 0 to 12 h (AUC 0−12 h ) on Day 43. Results Randomization failed to provide treatment groups with comparable baseline characteristics for smoking history, current smokers, duration of COPD, FEV 1, forced vital capacity (FVC) and reversibility. Mean±SD FEV 1 was 1.31±0.47 l in the tiotropium group vs. 1.46±0.53 l in the salmeterol plus fluticasone group. Fewer patients in the tiotropium showed a 12% and 200 ml acute increase to short-acting bronchodilators at baseline. However, treatment with tiotropium alone resulted in comparable bronchodilation compared with salmeterol plus fluticasone, as measured by all the spirometric parameters at the end of the 6-week study period. FEV 1 AUC 0–12 h was 1.55±0.03 l in the tiotropium group vs. 1.57±0.04 l in the salmeterol plus fluticasone groups ( p=0.63). Trough (predose) FEV 1 was 1.54±0.03 l in the tiotropium group vs. 1.46±0.03 l in the combination group ( p=0.07), and peak FEV 1 was 1.68±0.04 l vs. 1.66±0.04 l, respectively, ( p=0.77). FVC AUC 0–12 h , trough and peak were also comparable between groups at study end ( p>0.05, for all). Further, rescue salbutamol use was similar in the tiotropium and combination groups and both treatment regimens were well tolerated. Conclusions Six weeks of treatment with tiotropium resulted in comparable bronchodilation compared with salmeterol plus fluticasone in patients with moderate-to-very severe COPD, despite tiotropium patients having lower lung function and fewer patients considered reversible at baseline. The results of this pilot study will aid planning for further large-scale comparative studies.