Monday, September 23, 2019

Should we change how we treat mild asthma?

- Jennifer Middleton, MD, MPH

Inhaled corticosteroids are a mainstay for treating asthma; typically, they are prescribed on a scheduled basis, though many patients struggle with adherence. Two new studies may offer an alternative to scheduled inhaled corticosteroid dosing for patients with mild asthma.

As described in the "Top POEMS of 2018 Consistent with the Principles of the Choosing Wisely Campaign," these two randomized controlled trials compared the twice daily, scheduled use of budesonide (Pulmicort) to the as needed use of budesonide/formoterol (Symbicort) in patients with mild asthma. These researchers defined mild asthma as
asthma being uncontrolled while the patient was using short-acting bronchodilators as needed or as asthma that was well-controlled while the patient was using low-dose glucocorticoid or leukotriene-receptor antagonist maintenance therapy plus a SABA [short-acting beta agonist] as needed.
In the Symbicort Given as Needed in Mild Asthma (SYGMA) 1 trial, researchers randomized participants aged 12 years and older into three groups: twice daily placebo with an as needed terbutaline (a SABA) inhaler, twice daily placebo with as needed budesonide-formoterol, and twice daily budesonide with as needed terbutaline. Participants recorded daily peak expiratory flows, asthma symptoms, and nighttime awakenings using an electronic diary, and an electronic inhaler monitor recorded use of their as-needed inhaler. The researchers' primary outcome was "electronically recorded weeks of well-controlled asthma," a composite of all of these variables along with any documented additional prescribing of steroids (inhaled and/or oral). The as needed budesonide-formoterol group was superior to the as needed terbutaline group regarding mean percentage of weeks of well-controlled asthma (odds ratio 1.14, 95% confidence interval [CI] 1.00-1.30). The as needed budesonide-formoterol group was inferior to the maintenance budesonide group regarding weeks of well-controlled asthma (0.64, 95% CI 0.57-0.73), though there was no statistically significant difference regarding the secondary outcome of severe exacerbation occurrences in these two groups.

In the SYGMA 2 trial, the same group of researchers randomized participants aged 12 years and older into two groups to specifically focus on the outcome of severe exacerbations: as needed budesonide-formoterol versus maintenance budesonide. In contrast to the SYGMA 1 trial, where participants received daily reminders to use their inhalers, SYGMA 2 participants received no reminders. The researchers report that their preliminary results found a lower rate of exacerbations than anticipated (possibly because participants' inhaler adherence was also higher than anticipated), resulting in inadequate power with their sample size to demonstrate superiority of one group. They subsequently amended their study protocol to instead demonstrate noninferiority between the groups. The as needed budesonide-formoterol group had a 75% lower median dose of inhaled glucocorticoids than the maintenance budesonide group.

Both SYGMA trials offer the promise of less frequent inhaled steroid use for patients with mild asthma, though the results might not be convincing enough yet to change practice. Better powered studies would be useful to clarify 1) whether the trade-off of decreased steroid exposure is worth somewhat poorer weekly asthma control, and 2) whether there truly is any superiority between as needed budesonide-formoterol compared to maintenance budesonide regarding exacerbation rates. You can count on AFP to report the results of any future research and/or guideline changes; in the meantime, there's an AFP By Topic on Asthma if you'd like to read more (which includes this 2019 FPIN Clinical Inquiry on the use of intravenous magnesium to treat exacerbations in the emergency department).