PHARMACOLOGY CONSULT
What is the best way to step down therapy in patients with well-controlled asthma? Wendy Brown, PharmD, PA-C, AE-C
ABSTRACT Evidence suggests the best way to step down patients with well-controlled asthma on combination therapy is to lower the inhaled corticosteroid and eliminate the long-acting betaagonist (LABA). However, this approach has been challenged due to concerns over the long-term safety of LABAs. Until this safety concern is resolved, it is imperative that practitioners recognize well-controlled asthma and attempt step-down treatment with the goal of maintaining optimal asthma control with the least amount of medication. Keywords: asthma, long-acting beta-agonists, inhaled corticosteroids, step-down, well-controlled, Childhood Asthma Management Program
T
he FDA and national guidelines agree that therapy should be stepped down in patients whose asthma has been well controlled for 3 consecutive months.1,2 In June 2010, the FDA announced new recommendations that stated, “Once asthma control is achieved and maintained, patients should be assessed at regular intervals, and step-down therapy should begin (e.g., discontinue LABA) if possible without loss of asthma control, and the patient should continue to be treated with a long-term asthma control medication, such as an inhaled corticosteroid.”1 This statement leaves practitioners with a dilemma: follow the FDA recommendation and discontinue the LABA first, or follow national guidelines that recommend tapering the inhaled corticosteroid to a low dose before discontinuing the LABA. WHAT THE LITERATURE SUGGESTS For most patients, especially children with persistent asthma, a low-to-medium dosage of inhaled corticosteroid as a controller or maintenance therapy provides maximum
Wendy Brown is a certified asthma education, clinical coordinator for the North Dakota Pharmacy Services Corp.’s About the Patient program, and an associate professor at North Dakota State College of Pharmacy, Nursing and Allied Sciences in Fargo. The author discloses that she is a member of the Association of Asthma Educators speakers bureau. DOI: 10.1097/01.JAA.0000438535.76891.01 Copyright © 2014 American Academy of Physician Assistants
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www.JAAPA.com
benefit with minimal systemic effects.3 Identifying the lowest effective dose of inhaled corticosteroid is important in light of the recent long-term study data reported from the Childhood Asthma Management Program. The program has 12.5 years of data from children who are now adults with asthma. The findings demonstrated that although children given inhaled corticosteroids continued to grow, the 1.2 cm (0.47 inch) initial reduction in growth was not regained.4 This growth loss was most common as the inhaled corticosteroid dose increased and when inhaled corticosteroid therapy was initiated in children before puberty.4 As with any treatment, the risks and benefits must be weighed. Inhaled corticosteroids are preferred maintenance medications for treating asthma and have been shown to decrease mortality. Unlike other disease processes in which the practitioner often starts therapy low and slowly increases to therapeutic doses, asthma treatment is started at a high level to minimize the potential for permanent lung damage or airway remodeling secondary to the chronic inflammation that characterizes the disease. The initial therapy level or step is determined by the patient’s most severe symptoms or risk for exacerbations.2 Once control is maintained for 3 consecutive months, the practitioner should work with the patient (and caregivers as appropriate) to continually step down therapy at 3-month intervals until reaching the lowest possible dosage combination or monotherapy that maintains control.2 Several trials over the years have sought to determine the best step-down approach. In most trials, patients maintained symptom control, peak expiratory flow, forced expiratory volume in 1 second, and quality of life by decreasing the inhaled corticosteroid dose first, then discontinuing the LABA.5–8 The limitations to these trials were their short duration, which inadequately addresses the long-term safety of LABA use. LABAs may mask symptoms associated with increasing airway inflammation, predisposing patients to the need for hospitalization and intubation and increasing the risk of asthma-related death. LABAs should never be prescribed alone as maintenance therapy for asthma. The FDA has mandated additional safety trials on LABA and asthma, which are expected to be completed by 2017.9 Current best evidence supports identifying patients with Volume 27 • Number 1 • January 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
What is the best way to step down therapy in patients with well-controlled asthma?
well-controlled asthma and reevaluating therapy. In patients on combination therapy, providers may consider discontinuing the LABA or decreasing the inhaled corticosteroid to a low dose and then discontinuing the LABA. In keeping with dose titration strategies for inhaled corticosteroids, the National Heart, Lung and Blood Institute revised its asthma care quick reference in September 2012 (http://www.nhlbi.nih.gov/guidelines/asthma/asthma_quick ref.htm). This concise guide contains age-dependent dose titration tables for inhaled corticosteroids. The ultimate goal is to identify the minimal medication regimen that provides optimal control and drug safety for patients with asthma. The only treatment approach that would be inappropriate at this time for patients with well-controlled asthma is to not try to step down treatment. CONCLUSION Practitioners have a responsibility to identify patients with well-controlled asthma and have multiple options to provide step-down care. JAAPA REFERENCES 1. FDA Drug Safety Communication. New safety controls for long-acting inhaled asthma medications called long-acting beta-agonists (LABAs), medications used to treat asthma. Safety Announcement [02-18-2010]. FDA, 2010. http://www.fda.gov/ NewsEvents/Newsroom/PressAnnouncements/ucm200931.htm. Accessed August 8, 2013.
2. National Heart, Lung, and Blood Institute. Expert panel report 3: guidelines for the diagnosis and management of asthma. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed August 8, 2013. 3. Raissy HH, Kelly HW, Harkins M, Szefler SJ. Inhaled corticosteroids in lung diseases. Am J Respir Crit Care Med. 2013;187(8): 798-803. 4. Kelly HW, Sternberg AL, Lescher R, et al. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012;367(10):904-912. 5. Fowler SJ, Currie GP, Lipworth BJ. Step-down therapy with low-dose fluticasone–salmeterol combination or medium-dose hydrofluoroalkane 134a-beclomethasone alone. J Allergy Clin Immunol. 2002;109(6):929-935. 6. Bateman ED, Jacques L, Goldfrad C, et al. Asthma control can be maintained when fluticasone propionate/salmeterol in a single inhaler is stepped down. J Allergy Clin Immunol. 2006;117(3): 563-570. 7. Godard P, Greillier P, Pigearias B, et al. Maintaining asthma control in persistent asthma: comparison of three strategies in a 6-month double-blind randomised study. Respir Med. 2008; 102(8):1124-1131. 8. Reddel HK, Gibson PG, Peters MJ, et al. Down-titration from high-dose combination therapy in asthma: removal of longacting beta(2)-agonist. Respir Med. 2010;104(8):1110-1120. 9. FDA Drug Safety Communication. FDA requires postmarket safety trials for long-acting beta-agonists (LABAs). FDA, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm251512.htm. Accessed August 12, 2013.
ASK OUR CONSULTANT To ask our consultant a drug-related question, please e-mail [email protected].
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
What is the best way to step down therapy in patients with well-controlled asthma? Wendy Brown, PharmD, PA-C, AE-C
ABSTRACT Evidence suggests the best way to step down patients with well-controlled asthma on combination therapy is to lower the inhaled corticosteroid and eliminate the long-acting betaagonist (LABA). However, this approach has been challenged due to concerns over the long-term safety of LABAs. Until this safety concern is resolved, it is imperative that practitioners recognize well-controlled asthma and attempt step-down treatment with the goal of maintaining optimal asthma control with the least amount of medication. Keywords: asthma, long-acting beta-agonists, inhaled corticosteroids, step-down, well-controlled, Childhood Asthma Management Program
T
he FDA and national guidelines agree that therapy should be stepped down in patients whose asthma has been well controlled for 3 consecutive months.1,2 In June 2010, the FDA announced new recommendations that stated, “Once asthma control is achieved and maintained, patients should be assessed at regular intervals, and step-down therapy should begin (e.g., discontinue LABA) if possible without loss of asthma control, and the patient should continue to be treated with a long-term asthma control medication, such as an inhaled corticosteroid.”1 This statement leaves practitioners with a dilemma: follow the FDA recommendation and discontinue the LABA first, or follow national guidelines that recommend tapering the inhaled corticosteroid to a low dose before discontinuing the LABA. WHAT THE LITERATURE SUGGESTS For most patients, especially children with persistent asthma, a low-to-medium dosage of inhaled corticosteroid as a controller or maintenance therapy provides maximum
Wendy Brown is a certified asthma education, clinical coordinator for the North Dakota Pharmacy Services Corp.’s About the Patient program, and an associate professor at North Dakota State College of Pharmacy, Nursing and Allied Sciences in Fargo. The author discloses that she is a member of the Association of Asthma Educators speakers bureau. DOI: 10.1097/01.JAA.0000438535.76891.01 Copyright © 2014 American Academy of Physician Assistants
10
www.JAAPA.com
benefit with minimal systemic effects.3 Identifying the lowest effective dose of inhaled corticosteroid is important in light of the recent long-term study data reported from the Childhood Asthma Management Program. The program has 12.5 years of data from children who are now adults with asthma. The findings demonstrated that although children given inhaled corticosteroids continued to grow, the 1.2 cm (0.47 inch) initial reduction in growth was not regained.4 This growth loss was most common as the inhaled corticosteroid dose increased and when inhaled corticosteroid therapy was initiated in children before puberty.4 As with any treatment, the risks and benefits must be weighed. Inhaled corticosteroids are preferred maintenance medications for treating asthma and have been shown to decrease mortality. Unlike other disease processes in which the practitioner often starts therapy low and slowly increases to therapeutic doses, asthma treatment is started at a high level to minimize the potential for permanent lung damage or airway remodeling secondary to the chronic inflammation that characterizes the disease. The initial therapy level or step is determined by the patient’s most severe symptoms or risk for exacerbations.2 Once control is maintained for 3 consecutive months, the practitioner should work with the patient (and caregivers as appropriate) to continually step down therapy at 3-month intervals until reaching the lowest possible dosage combination or monotherapy that maintains control.2 Several trials over the years have sought to determine the best step-down approach. In most trials, patients maintained symptom control, peak expiratory flow, forced expiratory volume in 1 second, and quality of life by decreasing the inhaled corticosteroid dose first, then discontinuing the LABA.5–8 The limitations to these trials were their short duration, which inadequately addresses the long-term safety of LABA use. LABAs may mask symptoms associated with increasing airway inflammation, predisposing patients to the need for hospitalization and intubation and increasing the risk of asthma-related death. LABAs should never be prescribed alone as maintenance therapy for asthma. The FDA has mandated additional safety trials on LABA and asthma, which are expected to be completed by 2017.9 Current best evidence supports identifying patients with Volume 27 • Number 1 • January 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
What is the best way to step down therapy in patients with well-controlled asthma?
well-controlled asthma and reevaluating therapy. In patients on combination therapy, providers may consider discontinuing the LABA or decreasing the inhaled corticosteroid to a low dose and then discontinuing the LABA. In keeping with dose titration strategies for inhaled corticosteroids, the National Heart, Lung and Blood Institute revised its asthma care quick reference in September 2012 (http://www.nhlbi.nih.gov/guidelines/asthma/asthma_quick ref.htm). This concise guide contains age-dependent dose titration tables for inhaled corticosteroids. The ultimate goal is to identify the minimal medication regimen that provides optimal control and drug safety for patients with asthma. The only treatment approach that would be inappropriate at this time for patients with well-controlled asthma is to not try to step down treatment. CONCLUSION Practitioners have a responsibility to identify patients with well-controlled asthma and have multiple options to provide step-down care. JAAPA REFERENCES 1. FDA Drug Safety Communication. New safety controls for long-acting inhaled asthma medications called long-acting beta-agonists (LABAs), medications used to treat asthma. Safety Announcement [02-18-2010]. FDA, 2010. http://www.fda.gov/ NewsEvents/Newsroom/PressAnnouncements/ucm200931.htm. Accessed August 8, 2013.
2. National Heart, Lung, and Blood Institute. Expert panel report 3: guidelines for the diagnosis and management of asthma. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed August 8, 2013. 3. Raissy HH, Kelly HW, Harkins M, Szefler SJ. Inhaled corticosteroids in lung diseases. Am J Respir Crit Care Med. 2013;187(8): 798-803. 4. Kelly HW, Sternberg AL, Lescher R, et al. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012;367(10):904-912. 5. Fowler SJ, Currie GP, Lipworth BJ. Step-down therapy with low-dose fluticasone–salmeterol combination or medium-dose hydrofluoroalkane 134a-beclomethasone alone. J Allergy Clin Immunol. 2002;109(6):929-935. 6. Bateman ED, Jacques L, Goldfrad C, et al. Asthma control can be maintained when fluticasone propionate/salmeterol in a single inhaler is stepped down. J Allergy Clin Immunol. 2006;117(3): 563-570. 7. Godard P, Greillier P, Pigearias B, et al. Maintaining asthma control in persistent asthma: comparison of three strategies in a 6-month double-blind randomised study. Respir Med. 2008; 102(8):1124-1131. 8. Reddel HK, Gibson PG, Peters MJ, et al. Down-titration from high-dose combination therapy in asthma: removal of longacting beta(2)-agonist. Respir Med. 2010;104(8):1110-1120. 9. FDA Drug Safety Communication. FDA requires postmarket safety trials for long-acting beta-agonists (LABAs). FDA, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm251512.htm. Accessed August 12, 2013.
ASK OUR CONSULTANT To ask our consultant a drug-related question, please e-mail [email protected].
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
