European researchers are questioning the benefits of inhaled glucocorticoids in reducing the risk of exacerbations among patients with severe or very severe COPD. A double-blind study of nearly 2,500 patients found that glucocorticoids do not have a significant impact on reducing COPD exacerbations.
An inhaled glucocorticoid is commonly prescribed as an adjunct to LAMA (tiotropium) and LABA (salmeterol) combination therapy for patients with severe or very severe COPD with a history of exacerbations.
The study, published in the New England Journal of Medicine, found the patients that underwent a phased withdrawal of inhaled glucocorticoids over 18 weeks did not have a significantly greater risk of exacerbations.
All patients started out with 18 μg of tiotropium delivered once daily, 50 μg of salmeterol xinafoate twice daily and 500 μg of fluticasone propionate twice daily by a metered-dose inhaler. Over 18 weeks, a group of patients, went from 1,000 μg of inhaled glucocorticoids to 500 μg, to 200 μg and then to 0 μg.
When the phased withdrawal was complete at week 18, those patients had a slight drop in FEV1 (38 mL) when compared to those who continued the inhaled glucocorticoid regimen. At the conclusion of the study, at 52 weeks, a similar difference (52 mL) was seen between the groups. However, the larger reduction of FEV1 from baseline “does not seem to be associated exacerbations,” the authors wrote.
Overall “the stepwise withdrawal of glucocorticoids was noninferior to the continuation of such therapy, with respect to the risk of moderate or severe exacerbations,” the authors concluded.
The study challenges current treatment guidelines which call for a triple therapy, including inhaled corticosteroids, for patients with severe COPD. It is unclear what immediate impact the European study might have on established therapies. (Learn more about the current recommended guidelines at the Global Initiative for Chronic Obstructive Lung Disease, or GOLD.
In a separate study of patients who were 66 years or older, Canadian researchers found that a combination therapy of long-acting β-agonists and inhaled corticosteroids (ICS) was associated with a modestly reduced risk of death (36.4% vs 37.3%) or COPD-related hospitalizations (27.8% vs. 30.1%).
The benefits of the LABA-ICS combination therapy was greater in patients with a comorbidity of asthma with a difference in composite outcome at 5 years reaching -6.5% (at 95% confidence internal, and a hazard ratio of 0.84 at 95% CI) and those who were not receiving inhaled long-acting anticholinergic (LAA) drugs (-8.4%, 95% CI with HR of 0.79 at 95% CI).
Dr. Andrea Gershon, at the Sunnybrook Health Sciences Centre and Institute for Clinical Evaluative Sciences in Toronto, and her colleagues followed nearly 12,000 patients over eight years for the real-world, population-based study.
“Our finding of an association between LABAs and ICSs and outcomes helps clarify the management of patients with COPD and asthma, as many studies of COPD medications have excluded people with asthma and vice versa,” Dr. Gershon was quoted as saying by the Journal of the American Medical Association.
“In addition, practice guidelines for COPD recommend that LABAs be considered first-line treatment while asthma guidelines warn against use of LABAs without ICSs. Our findings also offer insight into the optimal treatment of COPD patients without asthma—those who would not be considered especially corticosteroid responsive.”