Drugs Slow COPD Progression

By Michael Smith
BOSTON, 16 aug 2008 -- For the first time, studies have shown that pharmacotherapy can slow the progression of chronic obstructive pulmonary disease, researchers here said.
In a large randomized controlled trial, the combination of fluticasone proprionate and salmeterol (Advair) reduced the decline in one-second forced expiratory volume (FEV1) by 16 mL a year compared with placebo, according to Bartolomé Celli, M.D., of Tufts, and colleagues.
The industry-sponsored study also showed that the inhaled corticosteroid fluticasone (Flonase) and the long-acting ß-agonist bronchodilator salmeterol (Serevent) -- when used alone -- had statistically similar benefits, Dr. Celli and colleagues reported in the second issue for August of the American Journal of Respiratory and Critical Care Medicine.
The finding came from a post-hoc analysis of the Toward a Revolution in COPD Health (TORCH) study, whose primary endpoint was reduction in mortality with the combination drug.
In February 2007, the researchers reported that the combination appeared to improve survival, but the difference from placebo was not significant. On the other hand, it significantly reduced exacerbations and improved overall health and lung function of patients compared with placebo. (See: Drug Combo Improves COPD Symptoms But Misses Mortality Endpoint)
Some details of the current analysis were presented later that year at the meeting of the American Thoracic Society. (See: ATS: COPD Drugs Slow Lung Function Decline)
TORCH was conducted from September 2000 to November 2005 in 42 countries and had 6,112 patients in the efficacy population, of which 5,343 had at least one measurement of FEV1 and were included in this analysis, the researchers said.
They were randomized to twice-daily placebo, 50 mcg of salmeterol, 500 mcg of fluticasone, or the combination medication at the same doses for three years.
Before the trial was unblended, the researchers decided to test the idea that the drugs would reduce the steady decline in FEV1 associated with COPD. They found that, over the three years:
The rate of decline of FEV1 for placebo patients was 55 mL a year, compared with 39 mL a year for those on the combination drug. The difference was significant at P<0.001.
The rate of decline for those on either drug alone was 42 mL a year, which was significantly different from placebo at P=0.003.
Dr. Celli and colleagues concluded that pharmacotherapy with the two drugs can slow the progression of COPD -- the only intervention other than smoking cessation that has been shown to do so.
They noted that the study was limited by a relatively high dropout rate, mainly in the placebo arm, and by the fact that FEV1 was not a primary endpoint of the original protocol.
The study offers "some hopeful signs for patients with COPD," said Samy Suissa, Ph.D., of McGill University in Montreal, writing in an accompanying editorial.
"For the first time, we have possible evidence that medications can modify the decline in lung function in COPD," Dr. Suissa wrote, adding that the study "also demonstrates that no treatment [placebo] is not an option for patients with moderate to severe COPD."
But Dr. Suissa also said the study shows clearly that using corticosteroids in COPD -- either alone or in combination -- "is unnecessary and thus inappropriate."
Since corticosteroids have a range of ill effects, he said, the choice of medication to use in COPD is "quite clear: it must be the long-acting ß-agonist bronchodilator."
The study was supported by GlaxoSmithKline. Dr. Celli reported reimbursement from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, and Almirall for participating in advisory boards and for lectures. Several other authors are employees of GlaxoSmithKline, hold equity in the company, or both.
Dr. Suissa reported financial links with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, and Sepracor.
Primary source: American Journal of Respiratory and Critical Care MedicineSource reference:Celli BR, et al "Effect of Pharmacotherapy on Rate of Decline of Lung Function in Chronic Obstructive Pulmonary Disease: Results from the TORCH Study" Am J Respir Crit Care Med 2008; 178: 332-338. Additional source: American Journal of Respiratory and Critical Care MedicineSource reference: Suissa S "Medications to Modify Lung Function Decline in Chronic Obstructive Pulmonary Disease: Some Hopeful Signs" Am J Respir Crit Care Med 2008; 178: 322-323.