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

Abstract

Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 microg versus placebo, inhaled via the Respimat Soft Mist Inhaler (SMI). The two studies were combined and had 4 co-primary endpoints (trough FEV(1) 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 FEV(1): 1.09 L). The mean trough FEV(1) response of tiotropium 5 or 10 microg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001). The COPD exacerbation rate was significantly lower with tiotropium 5 microg (RR = 0.78; P = 0.002) and tiotropium 10 microg (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 microg), 2.7% (10 microg), and 1.6% (placebo) of patients; these differences were not significant. Tiotropium Respimat SMI 5 microg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 microg dose but with a lower frequency of anticholinergic adverse events.

Keywords: COPD; FEV1; Respimat®; exacerbations; quality of life; tiotropium.

Figure 1

The adjusted mean (SEM) trough (a) FEV₁ (L) response and (b) FVC (L) response during 48 weeks of treatment with tiotropium 5 μg, tiotropium 10 μg, or placebo (n = 1897) (P < 0.0001 for tiotropium 5 μg–placebo and tiotropium 10 μg– placebo for mean improvement in FEV₁and FVC). Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; SMI, Soft Mist™ Inhaler.

Figure 2

Kaplan–Meier plot illustrating probability of remaining exacerbation-free over the 48-week treatment period (N = 1990) (P < 0.0001 for tiotropium 5 μg–placebo and tiotropium 10 μg–placebo for mean time [lower quartile] to first exacerbation). Abbreviations: COPD, chronic obstructive pulmonary disease; SMI, Soft Mist™ Inhaler.