Journal Article

Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study

Ferguson, Gary T, Calverley, Peter MA, Celli, Bartolome, Jones, Paul W, Yates, Julie C, Vestbo, Jörgen, Willits, Lisa R, Jenkins, Christine R, Anderson, Julie A

2009

Overview

Background The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented. However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease. Methods TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV 1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV 1 , 43% current smokers). To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV 1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937). Results Compared with placebo, SFC improved post-bronchodilator FEV 1 : 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV. SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage. Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV. The rates of adverse events were similar across treatment arms and increased with disease severity. Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages. Conclusion In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV 1 across GOLD stages. Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease. The effects were similar to those reported for the study as a whole. Thus, SFC is an effective treatment option for patients with GOLD stage II COPD. Trial registration Clinicaltrial.gov registration NCT00268216; Study number: SCO30003

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Aged / Albuterol - adverse effects / Albuterol - analogs & derivatives / Albuterol - therapeutic use / Analysis / Androstadienes - adverse effects / Androstadienes - therapeutic use / Bronchodilator Agents - adverse effects / Bronchodilator Agents - therapeutic use / Chronic obstructive lung disease / Clinical trials / Complications and side effects / Disease Progression / Dosage and administration / Double-Blind Method / Drug Combinations / Drug therapy / Drug therapy, Combination / Female / Fluticasone / Forced Expiratory Volume - physiology / Health aspects / Humans / Lung diseases, Obstructive / Male / Medical research / Medicine / Medicine & Public Health / Middle Aged / Mortality / Patient outcomes / Pneumology/Respiratory System / Pneumonia / Pneumonia - epidemiology / Pneumonia - physiopathology / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - mortality / Pulmonary Disease, Chronic Obstructive - pathology / Respiratory Function Tests / Salmeterol / Salmeterol Xinafoate / Smokers / Smoking - pathology