Tiotropium/olodaterol versus tiotropium in Japanese patients with COPD: results from the DYNAGITO study

Abstract

Masakazu Ichinose,1 Masaharu Nishimura,2 Manabu Akimoto,3 Yasuhiro Kurotori,3 Yihua Zhao,4 Alberto de la Hoz,5 Michiaki Mishima6 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Department of Pulmonary Medicine, Faculty School of Medicine, Hokkaido University, Sapporo, Japan; 3Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan; 4Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 5Boehringer Ingelheim International GmbH, Ingelheim, Germany; 6Osaka Saiseikai Noe Hospital, Osaka, Japan Background: The DYNAGITO study was a Phase IIIb, randomized, double-blind, multicenter, active-controlled, parallel-group, 52-week study designed to determine the efficacy and safety of tiotropium and olodaterol combination therapy (TIO+OLO 5/5 μg) versus tiotropium monotherapy (TIO 5 μg) for reducing moderate-to-severe exacerbations of COPD. This is a prespecified analysis of the DYNAGITO data in Japanese patients. Patients and methods: Enrolled patients had a diagnosis of COPD with at least one moderate-to-severe exacerbation in the previous 12 months. Of the total 7,880 treated patients in the DYNAGITO study, 461 (TIO+OLO 5/5 μg: n=226, TIO 5 μg: n=235) were Japanese. The primary endpoint was the annualized rate of moderate-to-severe COPD exacerbations. The key secondary endpoint was the time to first moderate-to-severe COPD exacerbation, and other secondary endpoints included the annualized rate of exacerbations leading to hospitalization, time to first COPD exacerbation leading to hospitalization, and all-cause mortality. Safety data were analyzed descriptively. Results: Combination therapy with TIO+OLO resulted in a 29% lower rate of moderate-to-severe COPD exacerbations relative to TIO monotherapy (rate ratio 0.71; 99% CI: 0.46, 1.10; p=0.0434). The risk of a first moderate-to-severe COPD exacerbation was 19% lower with TIO+OLO combination therapy than with TIO monotherapy (HR 0.81; 99% CI: 0.57, 1.17; p=0.1379), although this difference was not statistically significant. The annualized rate of COPD exacerbations requiring hospitalization was 14% lower in the TIO+OLO arm than in the TIO arm (rate ratio 0.86; 95% CI: 0.52, 1.42; p=0.5654). The adverse event incidence was balanced between treatment arms. Conclusion: In a prespecified subgroup analysis of Japanese patients in the DYNAGITO study, combination therapy with TIO+OLO was more effective than TIO in reducing exacerbations. Both treatments were well tolerated. Keywords: all-cause mortality, COPD, fixed-dose combination therapy, hospitalization, moderate-to-severe exacerbations, monotherapy

Keywords

• all-cause mortality
• COPD
• fixed-dose combination therapy
• hospitalization
• moderate-to-severe exacerbations
• monotherapy