Efficacy and safety of combining olodaterol Respimat? and tiotropium HandiHaler? in patients with COPD: results of two randomized, double-blind, active-controlled studies

摘要

Background: Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD). We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.Methods: Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat?) combined with tiotropium 18 μg once daily (via HandiHaler?) versus tiotropium 18 μg once daily (via HandiHaler?) combined with placebo (via Respimat?) in patients with moderate to severe COPD. Primary efficacy end points were area under the curve from 0–3 hours of forced expiratory volume in 1 second (FEV1 AUC0–3) and trough FEV1 after 12 weeks (for the individual trials). A key secondary end point was health status by St George's Respiratory Questionnaire (SGRQ) total score (combined data set).Results: Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0–3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points. These effects translated to improvements in SGRQ total scores (treatment difference –1.85; P<0.0001). The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.Conclusion: These studies demonstrated that olodaterol (Respimat?) and tiotropium (HandiHaler?) provided bronchodilatory effects above tiotropium alone in patients with COPD. In general, both treatments were well tolerated.