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

Eric Bateman1, Dave Singh2, David Smith3, Bernd Disse4, Lesley Towse5, Dan Massey5, Jon Blatchford5, Demetri Pavia5, Rick Hodder61Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa; 2University Hospital of South Manchester Foundation Trust, University of Manchester, Manchester, UK; 3North Bristol Lung Centre, Southmead Hospital, Bristol, UK; 4Boehringer Ingelheim, GmbH, Ingelheim, Germany; 5Boehringer Ingelheim, Ltd., Bracknell, Berkshire, UK; 6Divisions of Pulmonary and Critical Care Medicine, University of Ottawa, Ottawa, Ontario, CanadaAbstract: Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 μg versus placebo, inhaled via the Respimat® Soft MistTM 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.Keywords: COPD, exacerbations, FEV1, quality of life, Respimat®, tiotropiu