Clinical Question

Is single maintenance and reliever therapy (SMART) more effective than inhaled corticosteroids with or without long-acting beta agonists (LABA) as the controller and short-acting beta agonists (SABA) as relief therapy for asthma?

Bottom Line

When compared with standard therapy (inhaled corticosteroids with or without LABAs and SABAs as relief therapy), SMART is associated with a reduced risk of acute asthma exacerbations in patients 12 years or older. Evidence is limited for children four to 11 years of age. Fifteen of the 16 studies evaluated SMART vs. standard therapy using a combination of budesonide and formoterol (Symbicort) in a dry powder inhaler as needed to a maximum of 10 inhalations daily. (Level of Evidence = 1a–)

Synopsis

Until recently, standard therapy consisted of inhaled corticosteroids with or without LABAs as the controller therapy for patients with asthma, augmented with SABAs for as-needed quick relief of symptoms. These investigators thoroughly searched multiple sources, including Medline, Embase, the Cochrane databases, clinical trial registries, manufacturers' data, and bibliographic references, for studies that compared standard therapy with SMART, in which the combination of inhaled corticosteroids and LABA is used as the controller and quick relief therapy. No language restrictions were applied. Two reviewers independently evaluated potential studies for inclusion and used a standard scoring tool to assess methodologic quality. Disagreements were resolved by consensus discussion with a third reviewer. A total of 16 randomized controlled trials (N = 22,748 patients) met inclusion criteria. Of these, 15 evaluated SMART as a combination of budesonide and formoterol in a dry powder inhaler. Six of the studies were considered to have a high risk of bias; the rest were considered at low risk of bias. Asthma exacerbations included a composite outcome of requiring systemic corticosteroids, hospitalization, or emergency department visits.

Among patients at least 12 years of age, SMART was significantly associated with a reduced risk of asthma exacerbations compared with standard therapy with either the same or a higher dose of inhaled corticosteroids alone (number needed to treat [NNT] = 12.3; 95% confidence interval [CI], 8.7 to 22.2; and NNT = 9.1; 95% CI, 6.8 to 13.9, respectively). Similarly, SMART was significantly associated with a reduced risk of asthma exacerbations compared with standard therapy with either the same or a higher dose of inhaled corticosteroids and LABAs (NNT = 15.6; 95% CI, 9.8 to 38.5; and NNT = 37.0; 95% CI, 19.2 to 33.3, respectively). There was no significant difference in SMART vs. standard therapy in overall quality-of-life scores. Limiting the analysis to only studies at low risk of bias did not change the results. Only one trial evaluated SMART vs. standard therapy in children four to 11 years of age, and the results were inconclusive. A formal analysis for publication bias was not possible because of the small number of studies. Formal testing found minimal evidence of significant heterogeneity of results.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Reference: SobierajDMWeedaERNguyenEet alAssociation 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. JAMA2018;319(14):1485–1496.