Efficacy and safety of combining olodaterol Respimat® and tiotropium HandiHaler® in patients with COPD: results of two randomized, double-blind, active-controlled studies
Authors ZuWallack R, Allen L, Hernandez G, Ting N, Abrahams R
Received 9 August 2014
Accepted for publication 19 September 2014
Published 14 October 2014 Volume 2014:9(1) Pages 1133—1144
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
Richard ZuWallack,1 Lisa Allen,2 Gemzel Hernandez,2 Naitee Ting,2 Roger Abrahams3
1Saint Francis Hospital and Medical Center, Hartford, CT, USA; 2Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 3Morgantown Pulmonary Associates, Morgantown, WV, USA
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.
Keywords: bronchodilator, long-acting beta2-agonist, long-acting muscarinic antagonist, olodaterol Respimat®, tiotropium HandiHaler®
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]