The American Thoracic Society (ATS) has released a new clinical practice guideline on the pharmacologic management of chronic obstructive pulmonary disease (COPD). The guideline, published in the Annals of the American Thoracic Society, provides evidence-based recommendations on the use of long-acting beta-2 agonist (LABA)/long-acting muscarinic antagonist (LAMA) therapy, inhaled corticosteroids (ICS), and oral steroid therapies in patients with COPD.

Recommendations on LABAs/LAMAs

Based on current evidence with moderate certainty, the ATS panel made a strong recommendation for LABA/LAMA combination therapy vs LABA or LAMA monotherapy in patients with COPD who complain of dyspnea or exercise intolerance. The evidence stems from data from 24 randomized controlled trials of 45,441 participants with COPD. In these studies, dual LABA/LAMA therapy was associated with improvements in quality of life (QoL), significantly greater reductions in exacerbations, less overall breathlessness, and fewer hospitalizations compared with monotherapy. No differences were found between combination and monotherapy in terms of treatment-related adverse events.

A conditional recommendation was also made in the guideline which supports consideration of triple therapy with ICS/LABA/LAMA vs dual LABA/LAMA therapy in patients with COPD who complain of dyspnea or exercise intolerance despite treatment with LABA/LAMA. In particular, this recommendation is made for patients with COPD who have a history of at least 1 exacerbation in the past year that required antibiotics, oral steroids, or hospitalization. The recommendation was made based on 4 multicenter randomized trials with 9313 participants. Triple therapy in these studies resulted in fewer exacerbations and improvements in health-related QoL (HRQoL) but no significant improvements in dyspnea.


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Recommendations on ICS

The panel made another conditional recommendation with regard to ICS withdrawal in patients with COPD who are receiving triple ICS/LABA/LAMA therapy. Based on data from 2 large multicenter, randomized controlled trials, the ATS panel recommends withdrawing ICS in these patients if they have had no exacerbations in the past year. The evidence suggests that withdrawal does not reduce the risk of pneumonia, frequency of hospital admissions, COPD exacerbations, or death. Despite these findings, the panel suggests that ICS withdrawal could reduce costs, but no cost-effectiveness analyses were available to confirm this theory. Further research is needed on ICS withdrawal in patients with COPD who are receiving triple therapy, especially for specific subgroups.

In patients with blood eosinophilia (≥2% blood eosinophils or ≥150 cells/μl) and a history of at least 1 exacerbation in the past year that required antibiotics, oral steroids, or hospitalization, the panel suggests ICS could be considered as an additive therapy to a long-acting bronchodilator. No recommendation was made for or against ICS as an add-on therapy to long-acting bronchodilators in patients with COPD and without requirements for antibiotics, steroids, or hospitalization. This recommendation was based on results from 8 randomized controlled trials that showed a reduction in COPD exacerbation rates with ICS add-on in patients with blood eosinophils ≥2% or ≥150 cells/μl. No improvements were observed in dyspnea scores or HRQoL with the addition of ICS to long-acting bronchodilator therapy, however, and the addition of ICS may increase costs for patients.

Recommendations on Oral Steroid Therapy

Based on low certainty evidence from 4 trials, the ATS panel made a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations despite otherwise optimal therapy. The studies that provided the evidence for this recommendation did not demonstrate an improvement in clinical outcomes with maintenance oral steroid treatment. These studies, however, featured small sample sizes and were conducted over short periods of time.

Recommendations on Opioid-Based Therapy

Opioid therapy was associated with significant and clinically meaningful improvements in dyspnea in 14 randomized clinical trials of patients with COPD and advanced refractory dyspnea, according to the panel’s review of the literature. Thus, based on the very low certainty evidence available, the ATS recommended that opioid-based therapy could be considered for dyspnea management in patients with COPD who have advanced refractory dyspnea despite otherwise optimal therapy. The panel noted that this treatment should be based on a personalized approach of shared decision making.

Future Directions

In their conclusions, the ATS panel emphasized the need for shared decision making when applying these recommendations as a means of optimizing clinical care. Additionally, the panel wrote that more research is needed to form concrete recommendations on optimal pharmacologic therapy for patients with COPD and varying degrees of eosinophilia as well as for patients who are current and former smokers.

“The panel hopes that the research priorities outlined in this document will prompt new research needed to identify more specific patient profiles in order to provide personalized, patient-centered care,” the guideline committee wrote.

Reference

Gartman EJ, Mulpuru SS, Mammen MJ, et al. Summary for clinicians: clinical practice guideline on pharmacologic management of chronic obstructive pulmonary disease. Published online September 3, 2020. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.202007-880CME