The efficacy and safety of combined tiotropium and olodaterol via the Respimat® inhaler in patients with COPD: results from the Japanese sub-population of the Tonado® studies

Background: The efficacy and safety of once-daily tiotropium + olodaterol (T+O) maintenance treatment was demonstrated in the large, multinational, replicate, randomized, Phase III, Tonado (R) 1 (NCT01431274) and 2 (NCT01431287) studies in patients with moderate to very severe COPD. However, there may be racial differences in the effects of T+O on lung function in patients with COPD. Methods: In this Tonado (R) subgroup analysis, we assessed efficacy and safety of T+O in Japanese participants. Results: Versus the overall population, the 413 Japanese patients randomized and treated were slightly older, with more men, lower body mass index, lower baseline St George's Respiratory Questionnaire (SGRQ) scores, fewer current smokers, but with higher pack-year smoking history. A lower proportion of Japanese patients used inhaled corticosteroids, short-acting muscarinic antagonists, or short-or long-acting beta-adrenergic agonists at baseline, but use of long-acting muscarinic antagonists was higher. At Week 24, mean improvements with T+O 5/5 mu g in forced expiratory volume in 1 second area under the curve from 0-3 hours response were 151 mL versus olodaterol and 134 mL versus tiotropium 5 mu g; mean improvements with T+O 2.5/5 mu g were 87 mL versus olodaterol and 70 mL versus tiotropium 2.5 mu g. Mean improvements with T+O 5/5 mu g in trough forced expiratory volume in 1 second were 131 mL versus olodaterol and 108 mL versus tiotropium 5 mu g; mean improvements with T+O 2.5/5 mu g were 60 mL versus olodaterol and 47 mL versus tiotropium 2.5 mu g. SGRQ scores improved from baseline to a greater extent with both doses of T+O versus monotherapies. Responses were similar in the overall population. Adverse-event incidence was generally balanced across treatment groups. Conclusion: Consistent with results from the overall population, T+O 5/5 mu g was superior to each monotherapy for lung function and SGRQ in the Japanese sub-population of patients with COPD in Tonado (R).