Triple therapy for COPD demonstrates benefit, fails to meet end point in randomized study

Key Points

In a randomized, double-blind, parallel-group trial published in the Annals of Internal Medicine, triple therapy with tiotropium plus salmeterol (SAL) and fluticasone failed to reduce the proportion of patients with chronic obstructive pulmonary disease (COPD) experiencing exacerbations requiring treatment with systemic corticosteroids and/or antibiotics (the primary end point) compared with tiotropium plus salmeterol or tiotropium alone. However, the triple inhaled-drug regimen was associated with improvements in lung function and quality of life and decreased the number of COPD exacerbations requiring hospital admission.

In this trial, 449 patients with moderate-to-severe COPD (forced expiratory volume in 1 second [FEV₁]<65% of predicted) who had ≥1 COPD exacerbation in the past year were randomized to receive tiotropium 18 mcg once daily plus placebo twice daily (n=156), tiotropium 18 mcg once daily plus salmeterol 25 mcg twice daily (n=148), or triple therapy with tiotropium 18 mcg once daily plus fluticasone 250 mcg and salmeterol 25 mcg twice daily (n=145) for 52 weeks. Patients were selected from 27 Canadian medical centers. Secondary study end points included the number of COPD exacerbations requiring hospitalization, changes in quality of life as determined by the St. George's Respiratory Questionnaire, and improvements in lung function through the measurement of FEV₁.

Although triple therapy failed to achieve the primary end point, the treatment did reduce the number of exacerbations requiring hospitalization (incidence rate ratio=0.53; 95% CI, 0.33–0.86) and all-cause hospitalizations (incidence rate ratio=0.67; 95% CI, 0.45–0.99). Moreover, triple therapy demonstrated improvements in FEV₁ (P=.05) and COPD-related quality of life (P=.01) compared with tiotropium plus placebo.

The authors stated: "The clinical benefits of combining these drug classes must be balanced against the additional expense and potential inconvenience of adding another inhaler to an already complex treatment regimen."

The National Heart Lung and Blood Institute (NHLBI) estimates there are as many as 16 million people in the United States diagnosed with COPD; it is the fourth-leading cause of death in the United States and is estimated to result in nearly 750,000 hospitalizations annually.

SOURCES Aaron SD, Vandemheen KL, Fergusson D, et al; for the Canadian Thoracic Society/Canadian Respiratory Clinical Research Consortium. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: A randomized trial. Ann Intern Med. 2007;146:545–555.

Global initiative for chronic obstructive lung disease. Executive summary: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Available at: http:// http://www.goldcopd.org/guidelineitem.asp?l1=2&l2=1&intid=996. Accessed April 9, 2007.