Updates in the Pharmacological Management of COPD
Updates in the Pharmacological Management of COPD
Anh Nguyen, Pharm.D., Walgreens | M Health Fairview Bethesda
Background: Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death in the United States with more than 140,000 deaths each year. Although there is currently no cure for COPD, both pharmacological and non-pharmacological treatments can control symptoms, reduce frequency of exacerbations and improve quality of life (QOL). In April 2020, the American Thoracic Society (ATS) published updated guidelines on the pharmacologic management of COPD. Their recommendations resulted from a comprehensive literature review of studies between 1990 and July 2019. The ATS guidelines convey similar guidance as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 report, however there are some key features that differentiate between guidelines.
Evidence: The purpose of the ATS guideline update was to address six specific questions related to pharmacological management of COPD. In question number one, ATS analyzed whether long-acting beta agonists (LABA) in combination with long-acting muscarinic antagonists (LAMA) was more effective than and as safe as either agent alone in patients with COPD who complain of dyspnea or exercise intolerance. The ATS strongly recommends the use of a LABA/LAMA in combination and concluded that dual therapy significantly reduces exacerbations and hospital admissions while also improving dyspnea and QOL. Additionally, ATS did not reveal any evidence of harm from dual therapy compared to monotherapy. The GOLD report also strongly recommends combination treatment with LABA/LAMA including evidence of increasing forced expiratory volume in one second (FEV1).
For question number two, ATS investigated if triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA was more effective than and as safe as dual therapy with LABA/LAMA in patients who complain of dyspnea or exercise intolerance despite the use of dual therapy. In patients who have a history of >1 exacerbations in the past year requiring antibiotics, oral steroids or hospitalization, ATS suggests the use of triple therapy with ICS/LABA/LAMA over dual therapy with LABA/LAMA. The ATS noted although triple therapy increases the risk of pneumonia, the benefits of exacerbation reduction outweighs this risk.The GOLD guidelines also endorse triple therapy with ICS/LABA/LAMA and report evidence of improved lung function, increased health status and reduction of exacerbations compared to ICS/LABA, LABA/LAMA or LAMA alone.GOLD also mentions these effects are more prominent in patients “who are severely symptomatic, have moderate to very severe airflow obstruction, and a history of frequent and/or severe exacerbations.”
In question number three, ATS examined whether the ICS should be withdrawn in patients with COPD who are on triple therapy with ICS/LABA/LAMA. The ATS recommends ICS can be withdrawn in patients with no exacerbations in the past year, conveying there was no statistically significant difference in risk of pneumonia, all-cause mortality, or risk of exacerbation. On the other hand, the GOLD guidelines caution against de-escalating ICS in patients who were severely symptomatic, with moderate to severe airflow obstruction, and had a history of frequent and/or severe exacerbations before disease state stability. The studies in the GOLD guidelines report decreased FEV1 and increased exacerbations among patients with eosinophils >300 cells/uL.
For question number four, ATS evaluated whether treatment in patients with COPD and blood eosinophilia (>150 cells/uL) should include an ICS in addition to a long-acting bronchodilator. The ATS recommends ICS as additive therapy to a long-acting bronchodilator in patients with blood eosinophilia and a history of >1 exacerbation per year requiring antibiotics, oral steroids or hospitalization. On the contrary, the GOLD report suggests use of ICS may be considered in patients with one moderate COPD exacerbation per year or blood eosinophils 100-300 cells/uL. The GOLD guidelines more strongly supports the addition of an ICS with one or two long-acting bronchodilators in patients with a history of hospitalizations for COPD exacerbations, >2 moderate exacerbations of COPD per year, blood eosinophils >300 cells/uL, or history of, or concomitant, asthma.
In question number five and six, ATS explored if maintenance oral steroid therapy or opioid-based therapy is more effective than and as safe as no additional therapy in patients with COPD who have a history of severe and frequent exacerbations regardless of optimal therapy. ATS and GOLD both recommend against the use of maintenance oral corticosteroids, suggesting lack of benefit and increased harm such as side effects and steroid myopathy. In regards to opioid therapy, ATS suggests evidence of dyspnea improvement with opioid treatment and recommends treatment to be considered through shared-decision making. The GOLD report specifically mentions opiates, such as immediate-release morphine rather than synthetic opioids, along with neuromuscular electrical stimulation, oxygen and fans blowing air on to the face for palliative treatment of dyspnea.
Discussion and Clinical Impact: While the majority of the ATS recommendations for pharmacologic management of COPD were similar to the previously published GOLD 2020 report, the main difference was the blood eosinophils cut-offs for addition of an ICS. Both guidelines recommend the option to withdraw an ICS from treatment however the GOLD recommendations are more reserved. Although pharmacological therapy for COPD can control symptoms, reduce frequency of exacerbations and improve QOL, treatments have not been proven to prevent progression of disease or reduce mortality. When determining treatment for COPD, patient involvement through shared-decision making may be as important as safety, efficacy, and convenience.
Centers for Disease Control and Prevention. Disease of the week: COPD. Date last modified November 5th, 2019. https://www.cdc.gov/dotw/copd/index.html. Accessed May 25th, 2020.
Nici L, Mammen MJ, Charbek E, et al. Pharmacologic Management Of Chronic Obstructive Pulmonary Disease: An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;201(9):356-e69.
Global Initiative for Chronic Obstructive Lung Disease. Global Strategy For Diagnosis, Management, And Prevention Of Chronic Obstructive Pulmonary Disease 2020 Report.https://goldcopd.org/wp-content/uploads/2019/11/GOLD-2020-REPORT-ver1.0wms.pdf. Accessed May 6, 2020.