New therapy reduces mortality in patients with severe COPD

Jan 2 2008

Patients with severe COPD may benefit more from therapy that combines salmeterol and fluticasone [SFC] than treatment with tiotropium, according to results from a long-term, multi-center study, "Investigating New Standards for Prophylaxis in Reducing Exacerbations" (INSPIRE) that directly compared the two therapies.

“Although we found no difference in the overall rate of exacerbations between treatment groups, SFC treatment was associated with better health status, fewer patient withdrawals, and a lower mortality rate than occurred during tiotropium therapy,” said lead author if the study, Jadwiga Wedzicha, M.D., of the Royal Free & University College Medical School in London

This was the first large-scale trial to directly compare the two different treatment approaches. The results appeared in the first issue for January of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

The researchers recruited 1,323 patients with severe COPD and randomized them to receive one of two treatments—either SFC or tiotropium—for two years. They analyzed number and type of exacerbations, health status as measured by the St. George's Respiratory Questionnaire (SGRQ), lung function (post-dose forced expiratory volume in one second) and study withdrawal rate. The study was double-blinded and double-dummy controlled, and all patients underwent identical intensification of treatment before beginning the trial to standardize their clinical conditions.

While exacerbation rates between the two treatment groups were statistically indistinguishable, there were differences in the treatment that the exacerbations required. Oral corticosteroids were used more often to treat the tiotropium group, whereas patients on SFC required antibiotics more frequently.

“This finding provides indirect evidence that these treatments affect apparently similar patients in different ways that affect clinical judgment,” wrote Dr. Wedzicha in the article. “This difference warrants further study to determine the factors that affect therapeutic choice.”

There was also a small but statistically significant improvement in the SGRQ scores for patients on SFC. While this difference did not reach the standard of clinical significance, it did indicate that overall, SFC patients experienced a slightly higher overall quality of life and a post-hoc analysis revealed that more patients on SFC had a clinically significant improvement in health status than those on tiotropium therapy

Most strikingly, mortality was significantly lower in the SFC group during the study period, even though the trial was not powered to detect such a difference. There was more than a 50 percent reduction in the risk of on-therapy all-cause death at any time during the study period for the SFC patients. Patients undergoing SFC treatment were also significantly less likely to withdraw from the trial than others.

“Our study raises several important questions,” noted Dr. Wedzicha. “Why is there a difference between treatments" What is the biological basis of the differential effect on exacerbations, and is it related to the difference in mortality between the two treatments"”

Despite no difference in the overall rate of exacerbations between treatment groups, SFC treatment was associated with better health status, fewer patient withdrawals, and a lower mortality rate than occurred during tiotropium therapy and this may have important implications for the clinical management of COPD.

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