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Original Investigation
April 10, 2018

Association of Inhaled Corticosteroids and Long-Acting β-Agonists as Controller and Quick Relief Therapy With Exacerbations and Symptom Control in Persistent AsthmaA Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs
  • 2Division of Pulmonary and Critical Care Medicine, University of California, San Francisco
  • 3Center for Pharmacogenomics and Translational Research, Nemours Children’s Specialty Care, Jacksonville, Florida
  • 4Division of Allergy, Immunology, and Pulmonary Medicine, Duke University School of Medicine, Duke Children’s Hospital and Health Center, Durham, North Carolina
JAMA. 2018;319(14):1485-1496. doi:10.1001/jama.2018.2769
Key Points

Question  What is the efficacy associated with using inhaled corticosteroids and long-acting β-agonists (LABAs) together as both the controller and the quick relief therapy termed single maintenance and reliever therapy (SMART) in patients with persistent asthma?

Findings  In this meta-analysis that included 22 524 patients aged 12 years or older and 341 children aged 4 to 11 years with persistent asthma, SMART was associated with a significantly lower risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids and LABA as controller therapy, absolute risk difference, −2.8% for the older age group and −12.0% for the younger age group, although less robust data were available for this group.

Meaning  SMART was associated with better clinical outcomes than conventional approaches in patients with persistent asthma.

Abstract

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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