Efficacy and safety of tiotropium Respimat ® SMI in COPD in two 1-year randomized studies

Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 μg versus placebo, inhaled via the Respimat® Soft Mist™ Inhaler (SMI). The two studies were combined and had 4 co-primary endpoints (trough FEV1 response, Mahler Transition Dyspnea Index [TDI] and St George’s Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year). A total of 1990 patients with COPD participated (mean FEV1: 1.09 L). The mean trough FEV1 response of tiotropium 5 or 10 μg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001). The COPD exacerbation rate was significantly lower with tiotropium 5 μg (RR = 0.78; P = 0.002) and tiotropium 10 μg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001). Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment. Fatal events occurred in 2.4% (5 μg), 2.7% (10 μg), and 1.6% (placebo) of patients; these differences were not significant. Tiotropium Respimat® SMI 5 μg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 μg dose but with a lower frequency of anticholinergic adverse events.