PURPOSE:Previous studies in subjects with COPD suggest that combined therapy with inhaled β2-agonist and anticholinergics provide increased bronchodilation compared with monotherapies. This was a 2-week, multi-center, randomized, parallel group study designed to evaluate the efficacy and safety of concomitant treatment with nebulized arformoterol (the R,R-isomer of formoterol) and tiotropium DPI.
METHODS:COPD subjects (mean FEV1 1.37 L, ∼45.4 % predicted, ∼53% males) were randomized to receive monotherapy (either arformoterol 15μg BID [n=76] or tiotropium 18 μg DPI QD [n=80]), or concomitant therapy (nebulized arformoterol 15μg BID and tiotropium 18μg DPI QD [n=78]). Pulmonary function and other outcomes were examined, including time normalized FEV1AUC over 24 hours (primary endpoint) at week 2 compared to the study baseline.
RESULTS:The LSmean (±SE) FEV1AUC0–24 demonstrated greater improvement with combined therapy (0.22±0.2L) than with arformoterol (0.10±0.03L) or tiotropium (0.08±0.02L) alone (p-values <0.001). LSmean peak change in FEV1 was also greater for combined therapy (0.38±0.03L) than with either monotherapy (both 0.27±0.03L; p-values <0.05). The 24 hour trough FEV1 improved for all treatments, but was greatest with combined therapy (0.15±0.03L versus 0.08±0.03L [p= 0.07] for arformoterol and 0.09±0.02L [p= 0.05] for tiotropium alone). Mean levalbuterol use decreased for all treatment groups (combined therapy -2.5±2.3 actuations/day; -1.8±2.2 and -1.8±2.8 actuations/day for arformoterol and tiotropium, respectively). Dyspnea improvements (transition dyspnea index) were significantly greater with combined therapy (mean: +3.1±2.4 versus +2.3±2.4 for arformoterol and +1.8±2.8 for tiotropium; p ≤; 0.05). All treatments were well tolerated; with similar overall frequency of adverse events.
CONCLUSION:In subjects with COPD, pulmonary function, rescue medication use, and dyspnea were improved to a greater extent after combined treatment with arformoterol 15μg BID and tiotropium 18μg QD compared to monotherapy.
CLINICAL IMPLICATIONS:These results support greater improvement in pulmonary function, dyspnea, and reduced short acting bronchodilator use with combined treatment with arformoterol 15μg QD and tiotropium 18μg QD over either therapy alone among subjects with COPD.Study supported by Sepracor Inc.
DISCLOSURE:Donald Tashkin, Consultant fee, speaker bureau, advisory committee, etc. Dr. Tashkin participated in an Advisory Board meeting sponsored by Sepracor Inc.; No Product/Research Disclosure Information