Exacerbations of chronic obstructive pulmonary disease (COPD) are common and usually present as progressive dyspnea that often produces worsened lung function and can lead to fatal respiratory failure. Moreover, COPD exacerbations account for a significant proportion of healthcare expenditures. Prolonged courses of glucocorticoids for exacerbations can lead to additional complications such as worsened glycemic control, weight gain, and osteoporosis. Randomized controlled trials have supported the benefit of systemic glucocorticoids for COPD exacerbations, but the optimal dose and duration are not known, with current guidelines and practice patterns supporting moderate doses (e.g., 30–40 mg oral prednisone) for 10–14 days. Leuppi and colleagues (2013), therefore, carried out a randomized, double-blind, placebo-controlled trial to test the hypothesis that a shorter (5-day) course of steroids would be noninferior to a 14-day steroid course.
The Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE) study was carried out in 5 Swiss teaching hospitals, and 314 subjects (prior or current smokers without asthma) with acute COPD exacerbations presenting to the emergency department were enrolled over a 5-year period. Subjects were randomized to 5 or 14 days of oral prednisone (40 mg daily from day 2 onward after an initial IV dose of 40 mg methylprednisolone on day 1) or placebo and were followed for 180 days for the primary outcome of time to next exacerbation. All subjects received 7 days of broad-spectrum antibiotics, as well as inhaled steroids and beta-agonists and an inhaled long-acting anticholinergic. There was no significant difference in rates of re-exacerbation between the two treatment groups (37.2% short term vs 38.4% long term over 180 days), nor was there a significant difference in mortality or recovery of lung function. The 14-day treatment group experienced significantly higher (65%) prednisone exposure than the 5-day group, although there was no significant difference in treatment-related adverse events (e.g., hyperglycemia or hypertension) between the two groups. These findings met prespecified criteria for noninferiority of the 5-day steroid course compared with the 14-day course.
The authors acknowledge a number of limitations in their study, including lack of a standardized treatment protocol for COPD exacerbations at the time of trial design that they could employ in the study; the fact that all patients received antibiotics and a full range of inhaler therapy, perhaps leading to overtreatment of some patients with exacerbations; and a limitation in detecting development of glucocorticoid-related hypertension and/or hyperglycemia given that these events were monitored primarily in hospital and the length of hospitalization may have been insufficient to detect these outcomes. Furthermore, as recruited subjects were current or past smokers with severe or very severe COPD, the findings may not apply to all patients with COPD. Strengths of the study include the randomized, double-blind, placebo-controlled design and the rigorous statistical analysis that was carried out. In conclusion, the authors found that a shorter course of steroids (5 days) was noninferior to a longer steroid course (14 days) and furthermore that the short-term treatment group experienced significantly lower cumulative steroid exposure. While additional confirmative trials will be helpful, this study suggests that a shorter course of steroids may be sufficient for many patients with COPD exacerbations.
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