Short-Term Glucocorticoid Therapy for COPD
Exacerbations of chronic obstructive pulmonary disease (COPD) are risk factors for disease progression. Patients with COPD who experience frequent acute exacerbations are at increased risk for death. In a study cohort in Switzerland, 23% to 25% of patients with COPD experienced exacerbations that required pharmacologic treatment within 1 year.
International guidelines recommend a 7- to 14-day course of systemic glucocorticoid therapy (eg, 30-40 mg of oral prednisolone for 10-14 days) to manage acute exacerbations of COPD. Studies have demonstrated the clinical benefits of glucocorticoid therapy (improved outcome, reduced length of hospital stay, and accelerated recovery of FEV1 [forced expiratory volume in the first second]). The optimal dose and duration of systemic glucocorticoids have not been widely studied, however.
Noting that long-term use of systemic glucocorticoids is an independent risk factor for increased mortality in COPD, researchers recently conducted the REDUCE (Reduction in the Use of Corticosteroids in Exacerbated COPD) trial to determine whether short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbations is noninferior to conventional (14 day) treatment in clinical outcome and whether it decreases exposure to steroids. Trial results were reported online in JAMA [2013;309(21):doi:10.1001/jama.2013.5023].
The REDUCE trial was conducted at 5 teaching hospitals in Switzerland. The study cohort included 314 patients who presented to the emergency department from March 2006 through February 2011 with acute COPD exacerbation. The patients were past or present smokers (≥20 pack-years) with no history of asthma.
Patients were randomly assigned to either 5 or 14 days of systemic glucocorticoids
(40 mg of prednisone daily). The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15% (critical hazard ratio of 1.515 for a reference event rate of 50%). The primary outcome measure was time to the next exacerbation within 180 days.
The study included 314 patients who underwent randomization; of those, 3 were excluded due to incorrect initial COPD diagnosis. Of the remaining 311, 292 completed the 14-day treatment period and were included in the per-protocol analysis. Of the 311 eligible patients, 155 were assigned to conventional treatment and 156 to short-term treatment. The 2 cohorts were well matched in age, severity of airway obstruction, and pretreatment with glucocorticoids. The conventional group had more women compared with the short-term group (46.5% vs 32.7%; P=.02), but other baseline characteristics did not differ significantly between the 2 groups.
In the 180-day follow-up period, 35.9% (n=56) of patients in the short-term treatment group reached the primary end point of COPD exacerbation compared with 36.8% (n=57) in the conventional treatment group. There was no difference in time to re-exacerbation between the groups. There was no difference between the groups in time to death, the combined end point of exacerbation, death, or both, and recovery of lung function.
In the conventional treatment group, mean cumulative prednisone dose was significantly higher, but treatment-associated adverse events, including hyperglycemia and hypertension, did not occur more frequently.
The researchers summarized: “In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to re-exacerbation within 6 months of follow-up, but significantly reduced glucocorticoid exposure.”
