COPD: Combination Rx May Prolong Life, Improve Lung Function

From The American Thoracic Society

SAN DIEGO—Until recently, long-term oxygen therapy was the main approach to increasing survival for patients with chronic obstructive pulmonary disease (COPD). Now, 2 long-acting bronchodilators, fluticasone propionate/salmeterol (Advair) and tiotropium bromide (Spiriva), may allow patients with this common and debilitating disease to live longer and with improved lung function, according to new reports presented at the American Thoracic Society annual meeting.

“COPD no longer has to be seen as a chronic, relentless, and fatal disease. We can help patients live longer with a better quality of life,” said Claudia Cote, MD, assistant professor of medicine, University of South Florida, Tampa. “We should see COPD as a treatable disease and be aggressive in the management of our patients. Maybe then we’ll be able to impact survival.”

A large, retrospective, follow-up, historical, cohort study showed that patients with COPD lived longer if they used a fixed combination of the long-acting beta agonist salmeterol and the inhaled corticosteroid fluticasone together as 1 inhaler (Advair) or the 2 drugs concomitantly instead of short-acting beta agonist or inhaled corticosteroid monotherapy.

The 2521 COPD patients from 4 large managed care programs had been treated for ≥3 cumulative months. Three different statistical analyses were used to adjust for potential biases, according to Douglas Mapel, MD, MPH, medical director, Lovelace Clinic Foundation, Albuquerque, NM.

“Clearly, the combination of a long-acting beta agonist and inhaled corticosteroids was associated with substantially better survival than either product alone and significantly improved survival compared with short-acting beta agonists,” said Dr Mapel. “No other treatment shows improvement in survival in this disease.”

The survival benefit was attributed to the therapy, not to any clinical differences between treatment populations, he said. “Previously, COPD treatment has been symptomatic relief or palliative care. We now have a treatment that can affect the course of the disease by improving survival,” Dr Mapel added.

When asked whether physicians should therefore consider starting COPD treatment with a long-acting beta agonist/inhaled corticosteroid combination, Donald Tashkin, MD, of the University of California, Los Angeles, said, “We do not have enough data to make that recommendation. We need results from prospective, randomized controlled trials of Advair, not just retrospective data based on registration database criteria.”

The multicenter, multinational, double-blind trial TOwards a Revolution in COPD Health (TORCH) was the first pro-spective study to investigate the effects of pharmacotherapy on all-cause mortality in patients with COPD. Approximately 6200 participants were assigned to 1 of 4 treatments: fluticasone propionate/salmeterol (50/500 µg), salmeterol (Serevent; 50 µg), fluticasone (Flovent; 500 µg), or placebo.

Preliminary data released in March 2006 showed a 17% relative reduction in mortality over 3 years in the fluticasone propionate/salmeterol group versus the placebo group. But the results fell short of the main goal of achieving a statistically significant reduction in mortality.

Until the full results of the trial are available, Dr Tashkin suggests that physicians begin therapy with a long-acting beta agonist and then step-up therapy if needed, based on the patient’s response and severity of symptoms, to using a short-acting beta agonist as rescue medication. An inhaled corticosteroid can also be added for patients with severe disease and exacerbations.

In another study, tiotropium significantly improved pulmonary function and reduced exacerbations in African American COPD patients. This population is underrepresented in clinical trials and may respond differently to COPD treatment than whites, said Gerald Criner, MD, of Temple University, Philadelphia. People of African descent appear to be more susceptible to developing severe disease at a younger age despite similar levels of nicotine use.

The randomized, double-blind trial included 166 African American patients with COPD; 80 received tiotropium 18 µg once daily, while 86 matched controls received a placebo through an inhaler. After 8 weeks, the tiotropium-treated patients had significantly improved forced expiratory volume and forced vital capacity and fewer exacerbations compared with controls. There was no significant difference in the frequency of rescue medication use. Of note, the tiotropium group had a lower overall incidence of adverse events than the placebo group.

“These data are an important contribution establishing tiotropium as an effective treatment in patients of African descent,” said Dr Criner.