May 29, 2013
COPD Re-Exacerbation No Greater on Short-Course Steroids

Philadelphia—A 5-day glucocorticoid course of treatment for hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) was no less effective than a 14-day course for avoiding re-exacerbation during 6 months of follow-up, according to a new study.

The study, published early online by the Journal of the American Medical Association and presented simultaneously at the American Thoracic Society international conference, offers support for reducing glucocorticoid exposure and the risk of possible adverse effects, according to the authors.

“Acute exacerbations of COPD are a risk factor for disease deterioration, and patients with frequent exacerbations have an increased mortality,” according to background information in the article. “International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of COPD. However, the optimal dose and duration of therapy are unknown. … Given the adverse effects of glucocorticoids and the potentially large number of exacerbations occurring in patients with COPD, glucocorticoid exposure should be minimized.”

Researchers from the University Hospital of Basel, Switzerland, examined whether a short-term, 5-day, systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to the conventional 14-day treatment in reference to clinical outcomes and exposure to steroids.

Conducted from March 2006 through February 2011 at five Swiss teaching hospitals, the randomized trial enrolled 314 patients presenting to the emergency department with acute COPD exacerbation, all past or present smokers without a history of asthma. Patients, almost all of whom were admitted to the hospital, received treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled fashion, with the predefined noninferiority criterion being an absolute increase in exacerbations of at most 15%. The primary measured outcome was time to next exacerbation within 180 days.

Of the 314 randomized patients, 289 were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. In the short-term treatment group, 35.9% of patients reached the primary end point of COPD exacerbation compared with 36.8% in the conventional treatment group. Time to re-exacerbation did not differ between groups.

Among patients experiencing re-exacerbation during follow-up, the median time to event was 43.5 days in the short-term group and 29 days in the conventional treatment group. Estimates of re-exacerbation rates were 37.2% in the short-term and 38.4% in the conventional treatment group.

“There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean (average) cumulative prednisone dose was significantly higher (793 mg vs. 379 mg), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently,” the authors wrote.

The need for mechanical ventilation also did not increase with the short-term treatment regimen.

“There was no significant difference in recovery of lung function and disease-related symptoms, but the shorter course resulted in a significantly reduced glucocorticoid exposure,” according to the authors. “These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.”

An accompanying editorial from Don D. Sin, MD, and Hye Yun Park, MD, PhD, of the University of British Columbia James Hogg Research Centre and the Institute for Heart and Lung Health, St. Paul's Hospital, Vancouver, British Columbia, Canada, suggested that “the clinical implications of this study are clear.”

"Most patients with acute COPD exacerbations can be treated with a 5-day course of prednisone or equivalent (40 mg daily). Furthermore, this regimen can be applied across all GOLD (Global Initiative for Chronic Obstructive Lung Disease) categories of disease severity,” according to the commentary. “This is welcome news for patients with COPD who experience multiple exacerbations annually and are exposed to repeated courses of systemic corticosteroids. These findings will enable clinicians to minimize steroid exposure and reduce the risk of steroid-related toxicity in these patients."

U.S. Pharmacist Social Connect