Individuals treated with a single maintenance and reliever therapy (SMART) may have a lower risk for asthma exacerbations compared with individuals treated with inhaled corticosteroids (ICS) as the controller therapy and short-acting beta-agonists (SABA) as the relief therapy, according to a study published in the Journal of the American Medical Association.

Researchers performed a meta-analysis of 16 randomized clinical trials, with a combined total of 22,748 individuals (with a subgroup of patients ages 4-11 years [n=341]). Of the 16 studies identified, 15 evaluated the use of SMART consisting of budesonide and formoterol in a dry powder inhaler. The purpose of this systematic review was to determine the effects of SMART in individuals with persistent asthma. All of the studies included a SABA for individuals 5 years and older with persistent asthma for relief therapy.

The systematic review demonstrated SMART therapy in individuals 12 years or older with persistent asthma to be associated with a reduced risk for asthma exacerbations compared with both the same and higher doses of corticosteroids and long-acting beta-agonists (LABA) as the controller therapies (relative risk [RR], 0.68 [95% CI, 0.58-0.80]; risk difference [RD], –6.4% [95% CI, –10.2% to –2.6%] and RR, 0.77 [95% CI, 0.60-0.98]; RD, –2.7% [95% CI, –5.2% to –0.3%], respectively). 

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Only one study included individuals between the ages of 4 and11 years; however, results still found SMART to be associated with a reduced risk for asthma exacerbations compared with both the same and higher doses of corticosteroids and LABA as the controller therapies (RR, 0.55 [95% CI, 0.32-0.94]; RD, –12.0% [95% CI, –22.5% to –1.5%] and RR, 0.38 [95% CI, 0.23-0.63]; RD, –23.2% [95% CI, –33.6% to –12.1%], respectively).

The researchers found no association between SMART and all-cause mortality, regardless of comparative dose of ICS (2/3374 [0.06%] for SMART vs 5/3408 [0.15%] for the same dose of ICS and 3/2321 [0.13%] for SMART vs 1/3436 [0.03%] for a higher dose of ICS, respectively). In addition, there was no association between SMART vs ICS and LABA controller therapy at the same or higher doses on forced expiratory volume in 1 second, forced vital capacity, or percentage of predicted forced expiratory volume in 1 second. Finally, SMART was not associated with a reduced use of rescue medication per day (SABA) compared with the same or higher dose of ICS and LABA controller therapy.

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Researchers concluded that SMART was associated with a lower risk for asthma exacerbations compared with ICS as the controller therapy, and its use is consistent with the goals of current asthma management guidelines to reduce exacerbations and improve control. Although the literature was very limited for individuals 4 to11 years of age, the systematic review of the literature suggests that clinicians should consider the use of SMART for individuals 12 years of age and older with persistent asthma.


Sobieraj DM, Weeda ER, Nugyen E, et al. Association of inhaled corticosteroids and long-acting β-agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma: a systematic review and meta-analysis [published online March 19, 2018]. JAMA. doi:10.1001/jama.2018.2769