Clinical Question

Is an inhaled corticosteroid (ICS)/long-acting beta₂ agonist (LABA) combination effective as a relief medication in patients with mild to severe asthma when compared with a short-acting beta₂ agonist (SABA)?

Evidence-Based Answer

In mild asthma, as-needed ICS/LABA combinations should be used instead of as-needed SABAs without a maintenance inhaler because ICS/LABAs decrease the risk of severe exacerbations, increase the likelihood of having well-controlled asthma, and prolong the time to a first severe exacerbation. (Strength of Recommendation [SOR]: A, consistent, good-quality randomized controlled trials [RCTs].) In moderate to severe asthma, ICS/LABA single maintenance and reliever therapy (SMART) can decrease the risk of severe asthma exacerbations. (SOR: A, systematic review and meta-analysis of homogenous RCTs.) SMART had similar outcomes to other treatment regimens (ICS/LABA plus SABA) for forced expiratory volume in one second (FEV₁), symptom control, and safety.

Evidence Summary

A 2019 RCT lasting 52 weeks involved 668 patients 18 to 75 years of age with mild asthma who were from New Zealand and Europe. The trial compared the annualized rate of asthma exacerbations per patient in three treatment groups: ICS/LABA (budesonide/formoterol [Symbicort], one inhalation as needed); albuterol alone (100-mcg dose, two inhalations as needed from a pressurized metered dose inhaler); and budesonide (200 mcg, one inhalation twice daily) plus as-needed albuterol.¹ Two of the three arms focused on the reliever medication (n = 443). An exacerbation was defined as worsening asthma that resulted in one or more of the following: an urgent medical care consultation, prescription of systemic glucocorticoids for any duration, or an episode of high beta₂ agonist use (i.e., more than 16 actuations of albuterol or more than eight actuations of budesonide/formoterol over 24 hours). At 52 weeks, the annualized exacerbation rate in the budesonide/formoterol group was lower than in the as-needed albuterol group (absolute risk difference = 0.205; relative rate = 0.49; 95% CI, 0.33 to 0.72; number needed to treat = 5). The budesonide/formoterol group also had fewer severe exacerbations than the as-needed albuterol group (9 vs. 23; relative rate = 0.40; 95% CI, 0.18 to 0.86) and longer time to first exacerbation (hazard ratio = 0.46; 95% CI, 0.29 to 0.73). Symptom control scores measured by the Asthma Control Questionnaire (range = 0 to 6, with 6 indicating maximum impairment) were lower in the budesonide/formoterol group compared with the as-needed albuterol group (mean difference = −0.15; 95% CI, −0.24 to −0.06). The FEV₁ did not differ significantly between groups.