Triple therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD

¹ Medicines Evaluation Unit, University of Manchester, United Kingdom
² GlaxoSmithKline R&D, United Kingdom
³ Guy's, King's and St. thomas' School of Medicine, United Kingdom

^* To whom correspondence should be addressed. E-mail: dsingh{at}meu.org.uk.

Accepted 23 December 2007

	Abstract

Background: The combination of salmeterol and fluticasone propionate (SFC) and tiotropium bromide (TIO) are commonly used treatments in COPD but there is little data on their effectiveness when used together. We compared the effects of SFC 50/500mcg bd plus TIO 18mcg od with the individual treatments alone.

Methods: 41 COPD patients participated in a randomised, double-blind, double-dummy, 3-way cross-over study with 2-week wash-out periods between treatments. Lung function assessment included plethysmography and spirometry. The primary endpoint was post-dose specific airways conductance (sGaw) area-under the curve (AUC_0-4hr) on day 14.

Results: AUC_0-4hr sGaw was significantly higher on day 14 after SFC+TIO compared to TIO (22%) or SFC alone (27%), both p<0.001. SFC+TIO significantly improved trough FEV₁ compared with TIO alone (212mL, p<0.001) and SFC alone (110mL, p=0.017) on Day 14. Inspiratory capacity measurements also showed significant benefits for triple therapy over individual components on day 14. Subjects receiving SFC+TIO had clinically relevant improvements in TDI total score of 2.2 compared with TIO alone (p<0.001) (but not SFC alone, 0.7; p=ns) and used significantly less rescue medication (1.0 occasion less daily than TIO (p<0.001) and 0.6 less than SFC (p=0.01)).

Conclusion: SFC+TIO triple therapy led to greater improvements in bronchodilation compared with TIO and SFC alone. The advantages of triple therapy are observed across a range of physiologically important parameters, including airway conductance and lung volumes. Triple therapy also led to patient-related benefits by improving TDI and use of rescue medication.

Keywords: Chronic obstructive pulmonary disease, bronchodilation, combination therapy, salmeterol/fluticasone propionate, tiotropium