2007 OPEN FORUM Abstracts
SUSTAINED IMPROVEMENTS IN LUNG FUNCTION WITH FORMOTEROL PLUS TIOTROPIUM VS TIOTROPIUM ALONE DURING 12 WEEKS OF TREATMENT IN PATIENTS WITH STABLE COPD
D. Tashkin1, S. Varghese2
Background: Formoterol (FORM) and tiotropium (TIO) are long-acting bronchodilators that have different mechanisms of action in patients with chronic obstructive pulmonary disease (COPD). Previous studies in patients with stable COPD compared FORM and TIO with each other and with FORM+TIO combinations,1-3 but were of short duration. Two previous studies found that maximum improvements in forced expiratory volume in 1 second (FEV1) were greater with FORM alone than with TIO alone.1,3 We performed a longer term study to compare FORM+TIO with TIO alone in patients with stable COPD.
Methods: This was a 12-week, randomized, placebo-controlled, double-blind, multicenter study in COPD patients aged â¥40 years treated with FORM 12Î¼g BID and TIO 18Î¼g QD (n=116) or TIO 18Î¼g QD and placebo (n=124). The change from baseline in the area under the curve (AUC) for FEV1 measured 0 to 4 hours postmorning dose (FEV1 AUC0â4h) was the primary efficacy variable. Secondary efficacy variables included trough effects on FEV1 and effects on COPD symptoms.
Results: Significantly greater increases in FEV1 AUC0-4h were seen with FORM+TIO than with TIO alone at all time points postbaseline (P<0.001). After 12 weeks of treatment, the mean increase from baseline in the FEV1 AUC0-4h was 340 mL with FORM+TIO vs 170 mL with TIO. In addition, the increase from baseline in trough FEV1 was 180 mL with FORM+TIO vs 100 mL with TIO (P=0.004). The increases in lung function were accompanied by improvements in symptom scores that were sustained over 12 weeks with FORM+TIO (20%â32%) and significantly greater than improvements with TIO (9%â17%) at most study weeks. Both treatments were similarly well tolerated. These results expand on those of the earlier shorter-term studies of FORM+TIO combinations.1,2
Conclusions: In patients with stable COPD, combined treatment with FORM+TIO has greater therapeutic effects than treatment with TIO alone.
1 Cazzola M, Di Marco F, Santus P, et al. The pharmacodynamic effects of single inhaled doses of formoterol, tiotropium and their combination in patients with COPD. Pulm Pharmacol Ther 2004; 17:35-39
2 van Noord JA, Aumann JL, Janssens E, et al. Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD. Eur Respir J 2005; 26:214-222
3 Richter K, Stenglein S, Mucke M, et al. Onset and duration of action of formoterol and tiotropium in patients with moderate to severe COPD. Respiration 2006; 73:414-419