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

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 beta(2)-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 mu g once daily (via Respimat (R)) combined with tiotropium 18 mu g once daily (via HandiHaler (R)) versus tiotropium 18 mu g once daily (via HandiHaler (R)) combined with placebo (via Respimat (R)) 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 AUC(0-3)) 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 AUC(0-3) (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 (R)) and tiotropium (HandiHaler (R)) provided bronchodilatory effects above tiotropium alone in patients with COPD. In general, both treatments were well tolerated.