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TORCH FINDINGS SUPPORT COMBINATION THERAPY FOR COPD
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Key Point
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| Fluticasone/salmeterol combination therapy significantly improved the survival of COPD patients over a three-year interval whereas monotherapy with either drug provided no such benefit. |
SALT LAKE CITY—The results of the Towards a Revolution in COPD Health (TORCH) study, which were summarized and discussed at CHEST 2006, represent a major step forward in COPD management.1 In the study, Peter M.A. Calverley, MB, ChB, and colleagues found that combination therapy with fluticasone and salmeterol reduced all-cause mortality in a large population of COPD patients by 17.5% over three years. By contrast, fluticasone or salmeterol monotherapy did not affect the survival of these patients.
The combination of those drugs also reduced COPD exacerbations and improved the lung function and health-related quality of life of TORCH participants. "The combination therapy ... is the first intervention since oxygen therapy or smoking cessation to show improved survival in patients with COPD," claimed Bartolome R. Celli, MD, a principal study author and Chief of the Pulmonary, Critical Care, and Sleep Medicine Division of the Caritas-St. Elizabeth’s Medical Center in Boston.
EFFECTIVE TREATMENT FOR A COMMON CAUSE OF DEATH
The TORCH study was important because COPD is the fourth leading cause of death behind cardiovascular disease, pneumonia, and HIV/AIDS. Furthermore, it is the only major cause of death that is increasing worldwide.2,3
The study population consisted of 6,112 patients with moderate to severe COPD, as shown by an FEV1 of less than 60% predicted and by a mean value of 44% predicted after bronchodilator challenge. This population was 76% male, averaged 65 years of age, and had COPD patients from 46 countries; 43% of the patients were current smokers. The patients’ predicted FEV1 showed a mean improvement of 3.7% in response to albuterol.
In double-blind, randomized fashion, the patients were prospectively divided into four roughly equal groups that received one of the following COPD medication regimens twice daily: 500 mcg of fluticasone, 50 mcg of salmeterol, the combination of those two medications, or placebo.
The primary outcome measure was all-cause mortality at 156 weeks. The secondary end points were lung function, health-related quality of life, and the incidence of COPD exacerbations. Health-related quality of life is typically measured with such questionnaires as the SF-36 Health Survey, the St. George’s Respiratory Questionnaire, and the Chronic Respiratory Questionnaire.
Overall, there were 900 deaths during the three-year study period with mortality rates of 12.6% in the fluticasone/salmeterol group and 15.2% in the placebo group, related Dr. Celli. Compared to placebo, fluticasone/salmeterol combination therapy was associated with a hazard ratio for death from any cause of 0.825 (a 17.5% risk reduction).
The rates of death due specifically to COPD in the combination treatment and placebo groups were 6.0% and 4.7%, respectively. This difference translated to a hazard ratio for COPD-related mortality of 0.78 in the fluticasone/salmeterol group, but this finding was deemed a trend because it did not quite achieve statistical significance./font>
BETTER THAN MONOTHERAPY
In addition to improving the FEV1 and health-related quality of life of COPD patients, combination treatment produced about a 30% reduction in the risk of COPD exacerbations. "That included not just exacerbations where you took medicine but exacerbations that ended up in hospital admission," Dr. Celli pointed out.
When used alone, neither fluticasone nor salmeterol was more effective than placebo for preventing all-cause mortality. Compared to placebo, the hazard ratios for death from any cause with the two drugs were 1.06 and 0.88, respectively, but these differences were not significant.
No relationship was observed between all-cause mortality and baseline FEV1 by disease stage (based on the Global Initiative for Chronic Obstructive Lung Disease classifications). There were no significant interactions by smoking status, age, gender, or body mass index either.
"We do not know the exact mechanism by which this combined therapy works better than the separate therapies," Dr. Celli noted. "We speculate that synergistic action on cell receptors may lead to less muscle contraction or inflammation. Although we do not expect the combination therapy to replace existing therapies, it will allow greater room for intervention for health care providers treating patients with COPD."/font>
COMPLEMENTARY RESEARCH
Kardos and colleagues performed a similar study evaluating the effect of fluticasone/salmeterol combination treatment on moderate to severe exacerbations of COPD.4 Compared to salmeterol monotherapy, combination treatment resulted in a 35% lower incidence of such exacerbations. This study had 994 clinically stable COPD patients who were randomized to combination treatment or salmeterol monotherapy at the same doses and administration schedules used in the TORCH study.
—Timothy Begany
Reference
1. Calverley PM, Celli BR, Anderson JA, et al. The Towards a Revolution in COPD Health (TORCH) study: fluticasone propionate/salmeterol improves survival in COPD over three years. Presented at: annual meeting of the American College of Chest Physicians; October 24, 2006; Salt Lake City, UT.
2. Shahab L, Jarvis M, Britton J, West R. Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive pulmonary disease in a nationally representative population sample. Thorax. 2006; 61:1043-1047.
3. Goodridge D. People with chronic obstructive pulmonary disease at the end of life: a review of the literature. Int J Palliat Nurs. 2006;12:390-396.
4. Kardos P, Wencker M, Glaab T, Vogelmeier C. Impact of salmeterol/fluticasone propionate versus salmeterol on exacerbations in severe COPD. Am J Respir Crit Care Med. 2006; [Epub ahead of print].
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