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

Richard ZuWallack, Lisa Allen, Gemzel Hernandez, Naitee Ting, Roger Abrahams, Richard ZuWallack, Lisa Allen, Gemzel Hernandez, Naitee Ting, Roger Abrahams

Abstract

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®.

Figures

Figure 1
Figure 1
Design of ANHELTO 1 and ANHELTO 2.
Figure 2
Figure 2
Patient disposition (A) ANHELTO 1; (B) ANHELTO 2. Abbreviation: AE, adverse event.
Figure 3
Figure 3
FEV1 on day 1 in (A) ANHELTO 1; (B) ANHELTO 2, and at week 12 in (C) ANHELTO 1; (D) ANHELTO 2. Abbreviations: FEV1, forced expiratory volume in 1 second; h, hours.
Figure 4
Figure 4
FEV1 AUC0–3 response to treatment in (A) ANHELTO 1; (B) ANHELTO 2. Notes: ****P<0.0001 (olodaterol + tiotropium versus tiotropium + placebo); n=1,132 (ANHELTO 1), n=1,135 (ANHELTO 2). Abbreviation: FEV1 AUC0–3, area under the curve from 0–3 hours of forced expiratory volume in 1 second.
Figure 5
Figure 5
Trough FEV1 response to treatment in (A) ANHELTO 1; (B) ANHELTO 2. Notes: **P<0.01 (olodaterol + tiotropium versus tiotropium + placebo); n=1,132 (ANHELTO 1), n=1,135 (ANHELTO 2). Abbreviation: FEV1, forced expiratory volume in 1 second.

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Source: PubMed

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