Importance
Combined use of inhaled corticosteroids and long-acting
β-agonists (LABAs) as the controller and the quick relief therapy termed
single maintenance and reliever therapy (SMART) is a potential therapeutic regimen for the management of persistent asthma.
Objective
To conduct a systematic review and meta-analysis of the effects of SMART in patients with persistent asthma.
Data Sources and Study Selection
The databases of MEDLINE via OVID, EMBASE, the Cochrane
Central Register of Controlled Trials, and the Cochrane Database of
Systematic Reviews were searched from database inception through August
2016 and updated through November 28, 2017. Two reviewers selected
randomized clinical trials or observational studies evaluating SMART vs
inhaled corticosteroids with or without a LABA used as the controller
therapy and short-acting β-agonists as the relief therapy for patients
aged 5 years or older with persistent asthma and reporting on an outcome
of interest.
Data Extraction and Synthesis
Meta-analyses were conducted using a random-effects model to
calculate risk ratios (RRs), risk differences (RDs), and mean
differences with corresponding 95% CIs. Citation screening, data
abstraction, risk assessment, and strength of evidence grading were
completed by 2 independent reviewers.
Main Outcomes and Measures
Asthma exacerbations.
Results
The analyses included 16 randomized clinical trials
(N = 22 748 patients), 15 of which evaluated SMART as a combination
therapy with budesonide and formoterol in a dry-powder inhaler. Among
patients aged 12 years or older (n = 22 524; mean age, 42 years; 14 634
[65%] were female), SMART was associated with a reduced risk of asthma
exacerbations compared with the same dose of inhaled corticosteroids and
LABA as the controller therapy (RR, 0.68 [95% CI, 0.58 to 0.80]; RD,
−6.4% [95% CI, −10.2% to −2.6%]) and a higher dose of inhaled
corticosteroids and LABA as the controller therapy (RR, 0.77 [95% CI,
0.60 to 0.98]; RD, −2.8% [95% CI, −5.2% to −0.3%]). Similar results were
seen when SMART was compared with inhaled corticosteroids alone as the
controller therapy. Among patients aged 4 to 11 years (n = 341; median
age, 8 [range, 4-11] years; 69 [31%] were female), SMART was associated
with a reduced risk of asthma exacerbations compared with a higher dose
of inhaled corticosteroids as the controller therapy (RR, 0.55 [95% CI,
0.32 to 0.94]; RD, −12.0% [95% CI, −22.5% to −1.5%]) or the same dose of
inhaled corticosteroids and LABA as the controller therapy (RR, 0.38
[95% CI, 0.23 to 0.63]; RD, −23.2% [95% CI, −33.6% to −12.1%]).
Conclusions and Relevance
In this meta-analysis of patients with persistent asthma, the
use of single maintenance and reliever therapy compared with inhaled
corticosteroids as the controller therapy (with or without a long-acting
β-agonist) and short-acting β-agonists as the relief therapy was
associated with a lower risk of asthma exacerbations. Evidence for
patients aged 4 to 11 years was limited.
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