What Corticosteroid is Most Appropriate for treating Acute Exacerbations of CoPD?

Review of the Data

Administration route: intravenous (IV) vs. oral. The use of steroids in AECOPD began with such IV formulations as methylprednisolone, and this became the typical method of treating hospitalized patients. This practice was validated in a multicenter Veterans Affairs trial, which demonstrated decreased risk of treatment failure (defined as all-cause mortality, need for intubation, readmission for COPD, or intensification of pharmacologic therapy) for patients randomized to receive an IV-to-oral steroid regimen compared with those randomized to placebo.5 Patients receiving steroids also had shorter LOS and improvements in FEV1 after the first day of treatment. Subsequent randomized controlled trials in patients with AECOPD demonstrated the benefit of oral regimens compared with placebo with regard to FEV1, LOS, and risk of treatment failure.^6,7,8

Similarities in the bioavailability of oral and IV steroids have been known for a long time.⁹ Comparisons in efficacy initially were completed in the management of acute asthma exacerbations, with increasing evidence, including a meta-analysis, demonstrating no difference in improvement in pulmonary function and in preventing relapse of exacerbations for oral compared with IV steroids.¹⁰ However, only recently have oral and IV steroids been compared in the treatment of AECOPD. De Jong et al randomized more than 200 patients hospitalized for AECOPD to 60 mg of either IV or oral prednisolone for five days, followed by a week of an oral taper.¹¹ There were no significant differences in treatment failure between the IV and oral groups (62% vs. 56%, respectively, at 90 days; one-sided lower bound of the 95% confidence interval [CI], −5.8%).

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Table 1. Benefits and risks of steroid use in AECOPD

A large observational study by Lindenauer et al, including nearly 80,000 AECOPD patients admitted at more than 400 hospitals, added further support to the idea that oral and IV steroids were comparable in efficacy.¹² In this study, multivariate analysis found no difference in treatment failure between oral and IV groups (odds ratio [OR] 0.93; 95% CI, 0.84-1.02). The authors also found, however, that current clinical practice still overwhelmingly favors intravenous steroids, with 92% of study patients initially being administered IV steroids.¹²

Based on the evidence from de Jong and Lindenauer, it appears that there is no significant benefit to the use of IV over oral steroids. Additionally, there is evidence for oral administration being associated with beneficial effects on cost and hospital LOS.¹² Oral steroids, therefore, are the preferred route of administration to treat a hospitalized patient with AECOPD, unless the patient is unable to tolerate oral medications. Current guidelines support the practice of giving oral steroids as first-line treatment for AECOPD (see Table 2, above).

High dose vs. low dose. Another important clinical issue concerns the dosing of steroids. The randomized trials examining the use of corticosteroids in AECOPD vary widely in the dosages studied. Further, the majority of these trials have compared steroids to placebo, rather than comparing different dosage regimens. The agents studied have included prednisone, prednisolone, methylprednisolone, and hydrocortisone, or combinations thereof. In order to compare regimens of these different drugs, steroid doses often are converted into prednisone equivalents (see Table 3, below). Though no guidelines define “high dose” and “low dose,” some studies have designated doses of >80 mg prednisone equivalents daily as high-dose and prednisone equivalents of ≤80 mg daily as low-dose.^13,14

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Table 2. Comparison of recommendations from professional societies

Starting doses of systemic corticosteroids in the treatment of AECOPD in clinical studies range from prednisone equivalents of 30 mg daily to 625 mg on the first day of treatment.^5,8 No randomized studies of high- versus low-dose steroid regimens have been conducted. One retrospective chart review of 145 AECOPD admissions evaluated outcomes among patients who were given higher (mean daily dose >80 mg prednisone equivalent) and lower (mean daily dose of ≤80 mg prednisone) doses.¹⁴ The authors found that patients who received higher doses of steroids had significantly longer LOS compared with those who received lower doses, especially among the subset of patients who were admitted to the floor rather than the ICU, though this analysis did not adjust for severity of illness. In this study, the most striking finding noted by the authors was the wide variability in the steroid doses prescribed for the inpatient treatment of AECOPD.