In patients with acute COPD exacerbations, 5-day systemic glucocorticoid therapy was as effective as a conventional 14-day course of the drugs at preventing further exacerbations, according to a report published online May 21 in JAMA.
In a multicenter, randomized clinical trial, the 6-month rate of recurrent COPD exacerbation was 35.9% among patients who received the short course of systemic glucocorticoids, which was noninferior to the 36.8% rate among those who received the usual 2-week course, said Dr. Jörg D. Leuppi of the University Hospital of Basel (Switzerland) and his associates (JAMA 2013 May 21 [doi:10.1001/jama.2013.5023]).
The short-term approach’s main advantage is its significant reduction of patients’ exposure to glucocorticoids, which in turn will likely decrease short-term adverse effects such as hyperglycemia, weight gain, increased blood pressure, and insomnia, the investigators said. The short course also should prevent or delay longer-term steroid toxicities such as diabetes, osteoporosis, bone fractures, adrenal suppression, and ocular complications.
The investigators performed the noninferiority trial, known as the REDUCE (Reduction in the Use of Corticosteroids in Exacerbated COPD) study, because no adequately powered, randomized clinical trial has compared directly the outcomes of these two treatment durations. Despite that, "it has become quite common clinical practice to administer glucocorticoids in COPD exacerbations for shorter periods," the study authors noted.
The REDUCE trial’s results were published online and simultaneously reported at the annual meeting of the American Thoracic Society.
The study included 311 consecutive patients who presented with COPD exacerbations to emergency departments at five Swiss teaching hospitals during a 5-year period. All patients were older than 40 years, were current or past smokers, and had a smoking history of 20 or more pack-years.
All the study subjects received 40 mg of IV methylprednisolone on day 1, followed by 40 mg of oral prednisone on days 2-5. On days 6-14, 155 patients were randomly assigned to continue receiving oral prednisone (conventional therapy) and 156 to receive a matching placebo (short-course therapy). Patients, caregivers, and researchers were blinded to group assignment.
All the patients also received a broad-spectrum antibiotic for 7 days to prevent pneumonia; nebulized short-acting bronchodilators as needed while hospitalized; inhaled glucocorticoids combined with an inhaled beta-agonist twice daily; and inhaled tiotropium once daily. They all also received physiotherapy, supplemental oxygen, and ventilatory support according to accepted guidelines.
Patients who received short-course glucocorticoid therapy had a median cumulative prednisone dose of 200 mg and a mean cumulative dose of 379 mg. In contrast, those who received a longer duration of treatment had a median cumulative prednisone dose of 560 mg and a mean cumulative dose of 793 mg.
After 180 days of follow-up, 56 (35.9%) of patients in the short-course therapy group and 57 (36.8%) in the conventional therapy group reached the primary endpoint of a recurrent COPD exacerbation. The time to recurrence did not differ between the two groups.
In addition, the hazard ratios for experiencing a recurrence were nearly identical between the two study groups in both an intention-to-treat analysis and a per-protocol analysis, "meeting our noninferiority criterion," Dr. Leuppi and his colleagues said.
The findings remained robust in sensitivity analyses that adjusted for variables such as patient age and sex. They also persisted in subgroup analyses that compared patients who had different severities of underlying COPD and different past histories of glucocorticoid use.
Overall survival was not significantly different between patients who received 5 days and those who received 14 days of systemic glucocorticoids. The short-course therapy group also showed no increase in the need for mechanical ventilation during hospitalization.
Measures of forced expiratory volume in 1 second improved significantly in both groups by day 6 and remained stable thereafter, with "almost no differences" between groups. Patients in both groups reported significantly ameliorated dyspnea, as well as similarly improved bronchitis-related quality of life and overall performance.
Regarding short-term adverse effects of exposure to glucocorticoids, rates of new or worsening hypertension and new or worsening hyperglycemia were comparable between the two study groups. "We surmise that the length of hospital stay was insufficient to detect significant differences in blood pressure and blood glucose levels between groups, because these glucocorticoid adverse effects do not develop immediately after initiation of treatment," the researchers said.
There also were no differences in longer-term toxicities such as rates of infection, gastrointestinal bleeding, insomnia, fractures, psychiatric symptoms, or heart failure.
A surprising finding was that patients who received short-term glucocorticoids had a significantly shorter hospital stay (median, 8 days) than did those who received conventional glucocorticoids (median, 9 days). "Because we did not observe significant differences in glucocorticoid-related, short-term adverse effects, we cannot readily explain this observation, which might be a chance finding," Dr. Leuppi and his associates said.