Providing appropriate treatment options for patients with asthma when they reach the yellow zone is essential for de-escalating asthma exacerbations. A new treatment approach for patients in the yellow zone was presented by David M. Lang, MD, FACAAI, Chairman of the Department of Allergy and Clinical Immunology at the Respiratory Institute at the Cleveland Clinic. The new treatment approach is called “single inhaler therapy” or “SIT” (also been referred to as “dynamic dosing”). Importantly, the treatment is an off-label use for an FDA-approved product, specifically using budesonide and formoterol (BUD/FORM) for the management of patients with mild persistent asthma.
Dr. Lang illustrated an ideal case study where the use of BUD/FORM was appropriate and worked well for that particular patient. The patient in the case study was a young adult male with a lifelong history of asthma and allergic rhino conjunctivitis, who had taken inhaled corticosteroids (ICS) for more than 10 years and in the last year required two oral steroid courses. With the use of fluticasone/salmeterol 100/50 with one inhalation twice daily and an albuterol inhaler to take as needed, the patient had well-controlled asthma over the course of 6 months. However, at subsequent follow-up appointments, the patient continued to request to reduce the use of ICS, which presented an opportunity to use shared-decision making and discuss the risks of “stepping down” in managing his asthma. Following the guidelines for the “Stepwise Approach for Managing Asthma in Youths of 12 or more Years of Age and Adults,” Dr. Lang outlined the appropriate treatment reduction for the case study patient for each time the patient requested a reduction to use of ICS, that is the first step down was to fluticasone 88 mcg twice daily and albuterol inhaler as needed; and the second step down a year later was to BUD/FORM 80/4.5 used as maintenance and reliever (off-label use in the US). Dr. Lang advised the study patient to return if he used the BUD/FORM more than twice daily for the consideration of oral corticosteroids to help with an exacerbation.
Two recent studies published in the New England Journal of Medicine looked at BUD/FORM for different aspects of asthma therapy. Specifically, the SYGMA11 study analyzed whether BUD/FORM was superior over as needed terbutaline for asthma symptom control (measured by the number of well-controlled asthma weeks) and demonstrating non-inferiority of as-needed BUD/FORM versus BUD maintenance during well-controlled asthma weeks. BUD maintenance was superior over BUD/FORM as needed, and terbutaline as needed for well-controlled asthma weeks. Additionally, BUD/FORM significantly reduced the severe exacerbation rate and the time to first exacerbation compared with as-needed terbutaline. In comparison with the BUD maintenance treatment, BUD/FORM significantly reduced the severe exacerbation rate but, was similar in the time to first exacerbation. SYGMA2 examined the annualized rate of severe exacerbations and the total ICS exposure and time to first severe exacerbation between participants on BUD maintenance, BUD/FORM as needed, and terbutaline as needed. As-needed BUD/FORM was found to be non-inferior to BUD maintenance for severe exacerbations and the median ICS metered dose with as-needed BUD/FORM was reduced by 75% from that required with the BUD maintenance dose. Overall, adherence and time to first severe exacerbation were similar between the two treatment arms.
In addition to these studies a recent systematic review/meta-analysis by Sobieraj et al.3 found that BUD/FORM treatment was associated with a reduced number of subjects having exacerbations compared with: ICS/LABA as controller therapy at the same and higher dose.
Dr. Lang concluded that in “patients with mild persistent asthma who require controller therapy to provide protection from exacerbations, as-needed BUD/FORM is an additional treatment option for properly selected patients.”
1. O’Byrne, et al. N Engl J Med. 2018; 378:1865-76.
2. Bateman, et al. N Engl J Med. 2018; 378:1877-87.
3. Sobieraj w, et al. JAMA. 2018; 319:1485-96.