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

Abstract

BackgroundCombining 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.MethodsTwo 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).ResultsOlodaterol + 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.ConclusionThese 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.

Efficacy and safety of long-acting β-agonist/long-acting muscarinic antagonist combinations in COPD: a network meta-analysis

“…Allocation concealment was appropriate in 16 studies, and unclear in 3 studies. All trials presented intention-to-treat analyses except for two trials which excluded 2 patients out of 1134 and 1137 patients who did not receive the study treatment 26. Nineteen studies were double blinded (see online supplementary table S3).…”

“…Patients with asthma and other respiratory or cardiovascular disease were excluded in all trials. The concomitant use of a fixed dose of inhaled corticosteroids (ICS) was allowed in most studies, prohibited in two studies26 38 and unclear in one study35 which was addressed in a sensitivity analysis. A recent COPD exacerbation within a month of study entry was usually excluded from the study.…”

“…Two studies included a randomly assigned group that received tiotropium as an open-label treatment 30 37. The concomitant use of ICS was prohibited in two studies26 38 and unclear in one study 30. We performed a sensitivity analysis excluding these studies and the results were essentially unchanged.…”

Discovering the Relative Efficacy of Inhaled Medications for Chronic Obstructive Pulmonary Disease: Multiple Treatment Comparisons

“…Also, our study appears to support the above conclusions because patients with ICS+LABA+LAMA were significantly associated with better tFEV 1 , SGRQ and SGRQ Responders in relation to those with other inhaled medications. However, the potential for increased side effects with combining therapies has not been taken into consideration [29,33], and the use of steroids may raise potential risk for pneumonia [37]. As a result, whether the combination of ICS+LABA+LAMA can be a best choice for clinicians still need further proofs.…”

▼Olodaterol—another LABA for COPD

“…Two double-blind randomised studies have investigated the effect of olodaterol in combination with tiotropium 24. A total of 2,267 patients with a similar profile to those in the other trials were randomised to olodaterol 5μg once daily (via Respimat) plus tiotropium 18μg once daily (via HandiHaler) or placebo once daily (via Respimat) plus tiotropium 18μg once daily (via HandiHaler).…”