Prescribing Corticosteroids for COPD Exacerbations: Conservative and Short Trumps Liberal and Long

What is the optimal duration of corticosteroid therapy for COPD exacerbations?

Throughout their therapeutic lifetime, corticosteroids have proven to be a “double-edged sword.” Yes, they provide benefit (and may be lifesaving) in many diseases (a non-exhaustive list includes asthma, Crohn’s disease, systemic lupus erythematosus [SLE], and vasculitis), but they have serious downsides (another non-exhaustive list includes osteopenia, diabetes, cataracts, and infections). Another disease for which they provide benefit is chronic obstructive pulmonary disease (COPD) exacerbations. A lingering question in this regard persists, however. What is an optimum steroid dose, route of administration, and duration that provides positive therapeutic responses with a minimum of side effects?

EVIDENCE SHOWS LESS IS MORE

Leuppi and coworkers¹ attempted to answer these questions. First, they provided background. International guidelines suggest a 7- to 14-day course of systemic corticosteroids to treat exacerbations of COPD. The dose has varied between 30 and 40 mg of prednisone orally. However, lower doses have been tried, and in fact, also administered orally rather than parenterally. Importantly, outcomes were not worse with the conservative approach (a Cochrane review of 7 studies with an “n” of 280 patients was provided as proof in the paper). Enter the REDUCE trial which tested the hypothesis that a 5 day course of oral steroids (40 mg/day) would not be inferior to a 14 day course at the same dose.

Three hundred fourteen patients were randomized. Hazard ratios for the short-term versus conventional treatment group were 0.95; P = .006 for non-inferiority. This means that shorter treatment was not worse than longer. Time to next exacerbation was the hard end point. There were no differences between the conventionally treated versus conservatively treated groups regarding re-exacerbation rates, time to death, number of deaths, or recovery of lung function. Improvement in FEV₁ was present early, that is, for one third of those enrolled, within 5 days of treatment initiation. Most of the entrants in the study had severe COPD by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. This was not a group with mild disease for the most part.

The editorial commentary chose an appropriate title, “Steroids for Treatment of COPD Exacerbations: Less Is Clearly More.”²

A FEW CAVEATS ABOUT QUALITY

I grapple with 3 quality issues here. First, the prednisone works orally and does not require parenteral dosing. Second, the doses are not excessive, and when parenteral steroids are given, therapeutic doses as are prescribed in asthma or SLE are unnecessary and unsafe. Finally, prolonged or 2-week coverage is also unnecessary and not superior to shorter dosing periods. The message has to get to emergency departments and primary care offices that are still prescribing initial parenteral then oral steroids for 2 weeks. ■

REFERENCES:

1.Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease. The REDUCE Randomized Clinical Trial. JAMA. 2013;309(21):2223-2231. doi:10.1001/jama.2013.5023.

2.Sin DD, Park HY. Steroids for treatment of COPD exacerbations: less is clearly more. JAMA. 2013;309(21):2272-2273. doi. 10.1001/jama 2013.5644.