Withdrawal of Inhaled Corticosteroids in Patients with Stable Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, contributing to more than 120,000 deaths each year.^1,2 COPD is characterized by chronic airflow obstruction and a chronic inflammatory response that is progressive over time. Mainstays of therapy for COPD focus on reducing symptoms, preventing exacerbations, preventing disease progression, and reducing mortality, and include inhaled bronchodilators (beta₂-agonists and muscarinic antagonists) and inhaled corticosteroids (ICSs). Smoking cessation and vaccinations also play a role in preventing exacerbations and slowing disease progression, and systemic corticosteroids and antibiotics often play a role in the treatment of exacerbations.¹

Due to the progressive nature of COPD, a stepwise approach to escalation of therapy is recommended. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, most recently revised in 2011 and updated yearly, stage the severity of COPD based on 3 criteria: severity of airflow limitation (measured via spirometry as forced expiratory volume [FEV₁]), symptom assessment, and number of exacerbations per year.¹ The stages range from A (low risk, low symptoms) to D (high risk, more symptoms). Short-acting agents (short-acting beta₂-agonists and short-acting muscarinic antagonists) are first-line therapy options for early-stage COPD (GOLD group A). When a patient progresses to a more symptomatic disease (GOLD group B), a long-acting bronchodilator (long-acting beta₂-agonist [LABA] or long-acting muscarinic antagonist [LAMA]) is typically added to the short-acting, rescue therapy previously employed. If a patient begins to experience more exacerbations or a decrease in lung function (GOLD group C), the guidelines currently recommend use of a LABA plus an ICS or a single-agent LAMA.¹ This recommendation is based on data showing comparable efficacy of LABAICS therapy and LAMA therapy in terms of rate of COPD exacerbations.³ When a patient progresses to severe COPD (GOLD group D), LABA—LAMA–ICS triple therapy (or ICS–single bronchodilator therapy) is recommended.^1,4 Typically, once an ICS is added, it is not removed, due to concern for increasing the risk of exacerbations. However, recent data are beginning to shift the thinking on the necessity of continuing ICS therapy for COPD patients with stable disease.

The Case

JH is a 67-year-old woman who was given a diagnosis of COPD, 11 years ago. She has a history of multiple exacerbations and 2 hospitalizations (1 for pneumonia). However, she has not had an exacerbation in more than 1 year, due to successful smoking cessation and pulmonary rehabilitation. Her current COPD medications include Symbicort (160/4.5) 2 puffs twice daily, tiotropium 18 mcg once daily, and albuterol as needed. She is on 1 L of oxygen at home, and her most recent FEV₁ was 45% predicted. She is currently up-to-date on her influenza, PPSV23, and PCV13 vaccinations.

Discussion

Given the stable nature of JH’s COPD and that she currently has a reduced risk of exacerbations, it would be reasonable to consider gradually tapering off her ICS and leaving her on maintenance LABA-LAMA therapy. Doing so would not only be safe in terms of exacerbations, but could reduce her risk for infections and osteoporosis.

This recommendation is based on the 2016 updates to the GOLD guidelines: “Withdrawal of inhaled corticosteroids, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators.”¹ This update is based primarily on the OPTIMO trial and further supported by the WISDOM trial.^5,6 Both trials demonstrated that gradually withdrawing ICS therapy in patients with stable COPD did not increase the risk for exacerbations.

Adding further impetus to this recommendation are the recently published results of the FLAME trial, which demonstrated that indacaterol-glycopyrronium (LABA-LAMA) therapy was more effective than salmeterol-fluticasone (LABA-ICS) therapy in preventing COPD exacerbations in patients with a recent history of exacerbations.⁷ It also showed a decrease in rates of pneumonia in the LABA-LAMA group and similar rates of adverse events and deaths between the 2 groups. Other studies have also demonstrated improved lung function for patients on LABA-LAMA therapy versus LABA-ICS therapy.^8,9

Results from these studies demonstrate that the safe removal of an ICS in stable patients is well supported and can be considered in patients such as JH. Further, the results introduce the possibility of LABA-LAMA therapy becoming an alternative first choice to LABA-ICS therapy for patients with moderate to severe COPD.

Lori T. Armistead, PharmD, is a PGY1 ambulatory care pharmacy resident at the University of North Carolina Medical Center Department of Pharmacy in Chapel Hill.

References

• Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. goldcopd.org. Published December 2015. Updated 2016.
• NIH Fact Sheet: Chronic obstructive pulmonary disease (COPD). NIH Research Portfolio Online Reporting Tools (RePORT) website. report.nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=77. Published March 2013. Accessed July 7, 2016.
• Wedzicha JA, Calverley PM, Seemungal TA, Hagan G, Ansari Z, Stockley RA; INSPIRE Investigators. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177(1):19-26.
• Short PM, Williamson PA, Elder DHJ, Lipworth SIW, Schembri S, Lipworth BJ. The impact of tiotropium on mortality and exacerbations when added to inhaled corticosteroids and long-acting β-agonist therapy in COPD. Chest. 2012;141(1):81-86. doi: 10.1378/chest.11-0038.
• Rossi A, Guerriero M, Corrado A; OPTIMO/AIPO Study Group.. Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment of moderate COPD patients (OPTIMO). Respir Res. 2014;15:77. doi: 10.1186/1465-9921-15-77.
• Magnussen H, Disse B, Rodriguez-Roisin R, et al; WISDOM Investigators. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371(14):1285-1294. doi: 10.1056/NEJMoa1407154.
• Wedzicha JA, Banerji D, Chapman KR, et al; FLAME Investigators. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med. 2016;374(23):2222-2234. doi: 10.1056/NEJMoa1516385.
• Zhong N, Wang C, Zhou X, et al; LANTERN Investigators. LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:1015-1026. doi: 10.2147/COPD.S84436.
• Donohue JF, Worsley S, Zhu CQ, Hardaker L, Church A. Improvements in lung function with umeclidinium/vilanterol versus fluticasone propionate/salmeterol in patients with moderate-to-severe COPD and infrequent exacerbations. Respir Med. 2015;109(7):870-881. doi: 10.1016/j.rmed.2015.04.018.