For the first time, a drug therapy appears to reduce lung function loss in patients with moderate to severe chronic obstructive pulmonary disease (COPD), according to the results of a randomized, double-blind, placebo-controlled trial in 42 countries.
The Toward a Revolution in COPD Health (TORCH) study investigated the effects of combined salmeterol, a ß-agonist, and fluticasone propiniate, an inhaled cortical steroid, either alone or in combination, on mortality, exacerbations, health-related quality of life and rate of decline in lung function as measure by forced expiratory volume in one second (FEV1) in patients with COPD.
The results are published in the second issue for August of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
"Pharmacotherapy with salmeterol plus fluticasone propionate, or the components, reduces the rate of decline on FEV1 in patients with moderate to severe COPD, thus slowing disease progression," wrote Bartolome R. Celli, M.D., lead author of the study and professor at Tufts University School of Medicine. "To date, smoking cessation is the only intervention that has conclusively been shown to alter the rate of decline in FEV1," remarked Dr. Celli. This is the first demonstration of an effective pharmacothrerapy in COPD.
The TORCH study randomized more than 6,000 patients with moderate to severe COPD from 42 countries to receive either salmeterol (SAL; 50 g), fluticasone propionate (FP; 500 g), the two in combination (SFC; 50/500g), or placebo. After baseline FEV1 was recorded, patients were re-evaluated every 24 weeks to determine the rate of decline in FEV1.
"The rate of decline in FEV1 was slowest in patients on SFC and fastest in those randomized to the placebo arm," wrote Dr. Celli. "From week 24 onward, the adjusted rate of decline in FEV1 was 39ml/year for SFC, 42 ml/year for both SAL and FP and 55 ml/year for placebo."
Although the study was not formally powered to detect differences in rate of decline of FEV1, the results were highly significant (p<0.001.) The rate of decline in treatment groups was similar across a number of variables, including sex, age, ethnicity and body mass index. Furthermore, the slower rate of decline in FEV1 appeared to be associated with a lower risk of exacerbation.
"Although treatment did not abolish the accelerated decline in lung function [that occurs with COPD], it did ameliorate it substantially," wrote Dr. Celli, while noting that "the mechanism responsible for the effect on rate of decline is not clear, as all treatments have potentially significant nonbronchodilator effects." Clarifying those mechanisms is the goal of the next phase of the research, with the comparison between a long-acting bronchodilator drug and placebo with respect to FEV1 decline.
In the meantime, "the TORCH study brings some clarity to the treatment picture and provides some hopeful signs for patients with COPD," wrote Samy Suissa, Ph.D., of McGill University, in the accompanying editorial. "This study also demonstrates that no treatment [placebo] is not an option for patients with moderate to severe COPD."