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

Abstract

BackgroundThe 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 methodsEnrolled 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.ResultsCombination 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.ConclusionIn 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.

Comparison of Effectiveness Using Different Dual Broncho- dilator Agents in Chronic Obstructive Pulmonary Disease Treatment

“…[27][28][29] The DYNAGITO study was performed to compare the safety and efficacy of TIO/OLO dual therapy versus TIO monotherapy in reducing exacerbations in COPD patients with a history of at least one exacerbation in the previous 12 months and TIO+OLO combination therapy provided a numerically greater reduction in moderate-to-severe exacerbations than TIO monotherapy. [15] Besides, anti-inflammatory effects were the central role for reducing AE and combined with TIO plus OLO had the synergistic effect for reducing neutrophils inflammation in vitro study. [30] In fact, ideal dual bronchodilator agents should have these efficacy including: the decrease in hyperinflation and mechanical stress, the modulation of mucus production and mucociliary clearance, the improvement of symptoms fluctuation and severity, and some potential direct and indirect anti-inflammatory properties.…”

“…Tiotropium/olodaterol consistently improved 24-h lung function in 6-week studies, providing greater benefits than the monotherapies, placebo or twice-daily fixeddose fluticasone propionate/salmeterol. Worth noting, in the subgroup analysis from Tonado [14] and DYNAGITO study [15], combination therapy with TIO+OLO was more effective than TIO in reducing exacerbations in Japanese population compared with other races. Taken together including our results, TIO+OLO combination therapy may have a superior treatment efficacy in Asian population.…”

Reducing and managing chronic obstructive pulmonary disease exacerbations with tiotropium + olodaterol

“…Interestingly, a pre-specified subgroup analysis of Japanese patients in the DYNAGITO ® trial, FDC T+O reduced moderate-to-severe COPD exacerbations by 29% vs tiotropium monotherapy 64 .…”

The once-daily fixed-dose combination of olodaterol and tiotropium in the management of COPD: current evidence and future prospects

“…A total of 21% of the Japanese patients randomized in the TIO 5 µg discontinued the study versus 10% in the TIO/OLO 5/5 µg arm (discontinuation HR: 0.45; 95% CI: 0.27, 0.73), contrasting with the 16% versus 12% in the overall population (discontinuation HR: 0.73, 95% CI 0.65, 0.82). 65…”

“…Within the limitations of this exploratory analysis, it thus appears that TIO/OLO 5/5 µg exerted numerically larger effects on moderate-to-severe exacerbations in the Japanese subgroup, compared with the overall study population, an observation potentially related to differences in clinical characteristics between the two populations. 65…”