Effects of arformoterol twice daily, tiotropium once daily, and their combination in patients with COPD

SummaryPurposeCurrent guidelines support using in combination more than one class of long-acting bronchodilator for COPD patients whose symptoms are not controlled by mono-therapy. This 2-week, multi-center (34 sites), randomized, modified-blind, parallel group study evaluated the efficacy and safety of concomitant treatment with nebulized arformoterol (the formoterol(R,R)-isomer) BID and tiotropium DPI QD.MethodsCOPD patients (mean FEV1 1.37 L, 45.4% predicted) were randomized to receive mono-therapy (either arformoterol 15 μg BID [n = 76] or tiotropium 18 μg QD [n = 80]), or combined therapy (sequential dosing of arformoterol 15 μg BID and tiotropium 18 μg QD [n = 78]). Changes in pulmonary function, dyspnea, and rescue levalbuterol use were evaluated, as were safety outcomes.ResultsMean FEV1AUC0–24 (the primary endpoint) improved similarly from baseline for arformoterol (0.10 L) and tiotropium (0.08 L) treatment groups and greater for the combined therapy group (0.22 L; all p-values <0.005). Peak FEV1, peak FVC, 24-h trough FEV1, and inspiratory capacity also improved similarly for the mono-therapies and greatest for the combined therapy. Dyspnea (mean transition dyspnea index) improved similarly for arformoterol (+2.3) and tiotropium (+1.8) and greatest with combined therapy (+3.1; p-values <0.05). Levalbuterol use decreased for all treatment groups (range −1.8 to −2.5 actuations/day). All treatments had similar frequency of adverse events.ConclusionIn this study, the combination of nebulized arformoterol 15 μg BID plus tiotropium 18 μg DPI QD was the most effective in improving pulmonary function and disease symptoms. Mono-therapy improvement with arformoterol or tiotropium was similar. All three treatments were well tolerated.