Combo Treatment Works Best for COPD

Only Small Benefit Seen With Chronic Obstructive Pulmonary Disease Treatment

Medically Reviewed by Louise Chang, MD on February 21, 2007
From the WebMD Archives

Feb. 21, 2007-- A promising treatment for chronic obstructive pulmonary disease (COPD) failed to show a clear survival benefit in a large international trial, but improvements were seen in patient lung function and overall health.

The study looked at treatment with Advair Diskus 500/50, which combines an inhaled corticosteroid (Flovent) and a long-acting beta-agonist (Serevent).

Researchers compared treatment with the combination drug Advair with each of the therapies alone, and with no treatment, in patients with chronic obstructive pulmonary disease.

Compared with untreated patients, Advair-treated patients were 17.5% less likely to die of all causes during the three-year study.

While the reduction fell just short of reaching statistical significance, the trial’s author tells WebMD he believes the combined therapy can help patients live longer.

The study is published in the Feb. 22 issue of The New England Journal of Medicine.

“We came very close [to showing a survival advantage], but we didn’t quite make it,” says Peter M.A. Calverley, MD.

“We clearly showed that the combined treatment helps prevent disease-related exacerbations and helps people feel better," he says. "But does it help them live longer? We can’t say for sure; but we think it does.”

A Leading Killer

COPD, which includes emphysema and chronic bronchitis, is the fourth leading cause of death in the U.S.

The disease hampers the airflow of the airways, making it hard to breathe. It generally worsens over time.

Nearly 11 million American have been diagnosed with COPD, but it is widely believed millions more may have it.

The international study, known as the TORCH trial, included 6,112 patients in 42 countries who had moderate to severe COPD.

Roughly a quarter of the patients took Advair, which contains the corticosteroid, fluticasone propionate, and a long-acting beta-antagonist, salmeterol.

The remaining patients were treated with either the inhaled corticosteroid alone, the long-acting beta-agonist alone, or a placebo.

Beta-agonists like salmeterol work by relaxing the smooth muscles of the airways, which improves airflow.

Inhaled corticosteroids reduce inflammation, which is thought to play a role in COPD.

Study Results

A total of 875 patients died during the three-year study.

Deaths from all causes occurred in 12.6% of the combination treatment group, 13.5% of the group treated with the long-acting beta-agonist alone, 16% of those treated with the inhaled corticosteroid alone, and 15.2% of the placebo group.

Compared with no treatment, the combination treatment resulted in statistically meaningful improvements in lung function and less worsening of COPD-related symptoms.

Treatment with inhaled corticosteroids -- either alone or as part of the combination therapy -- was associated with an increase in pneumonia in the newly reported study.

Patients treated with either the combination therapy or the inhaled steroids alone were 60% more likely to be diagnosed with pneumonia. But, surprisingly, they were no more likely to die or be hospitalized than patients who did not receive corticosteroids.

“We don’t really know what this means,” Calverley says. “These patients had more pneumonias, but on average they felt better and had fewer flare-ups of their disease than [untreated] patients.”

Survival Advantage Probably Small

Calverley says the high dropout rate in the untreated (placebo) patients -- 44% compared with 34% of the Advair-treated patients -- could help explain the failure to show a clear survival advantage in patients with the combination treatment.

But pulmonary disease expert Klaus F. Rabe, MD, PhD, tells WebMD the new findings suggest that if a survival advantage exists, it is probably a small one.

Rabe, a professor of medicine at Leiden University Medical Center in the Netherlands, is chairman of the science committee of the Global Initiative for Obstructive Lung Disease.

“The hope had been that this would be a wonder drug that would stop people from dying of this disease, but that does not appear to be the case,” he says.

In an editorial accompanying the study, Rabe concludes that COPD patients should not be treated with inhaled corticosteroids alone.

“Combination therapy, as compared with monotherapy with long-acting beta-agonists or inhaled corticosteroids, offers statistically significant advantages for health status, frequency of exacerbations, use of oral steroids, and -- probably most important clinically -- protection against a decline in lung function,” he wrote.

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SOURCES: Calverley, P. New England Journal of Medicine, Feb. 22, 2007; vol 356: pp 775-789. Peter M.A. Calverley, MD, University Hospital Aintree, Liverpool, England. Klaus F. Rabe, MD, PhD, professor of medicine, Leiden University Medical Center, Leiden, the Netherlands. American Lung Association web site.

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