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JAMA. 2018 Apr 10;319(14):1473-1484. doi: 10.1001/jama.2018.2757.

Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma: A Systematic Review and Meta-analysis.

Author information

1
Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs.
2
Division of Pulmonary and Critical Care Medicine, University of California, San Francisco.
3
Center for Pharmacogenomics and Translational Research, Nemours Children's Specialty Care, Jacksonville, Florida.
4
Division of Allergy, Immunology, and Pulmonary Medicine, Duke University School of Medicine, Duke Children's Hospital and Health Center, Durham, North Carolina.

Erratum in

Abstract

Importance:

Long-acting muscarinic antagonists (LAMAs) are a potential adjunct therapy to inhaled corticosteroids in the management of persistent asthma.

Objective:

To conduct a systematic review and meta-analysis of the effects associated with LAMA vs placebo or vs other controllers as an add-on therapy to inhaled corticosteroids and the use of a LAMA as add-on therapy to inhaled corticosteroids and long-acting β-agonists (LABAs; hereafter referred to as triple therapy) vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma.

Data Sources:

MEDLINE, EMBASE, Cochrane databases, and clinical trial registries (earliest date through November 28, 2017).

Study Selection:

Two reviewers selected randomized clinical trials or observational studies evaluating a LAMA vs placebo or vs another controller as an add-on therapy to inhaled corticosteroids or triple therapy vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma reporting on an outcome of interest.

Data Extraction and Synthesis:

Meta-analyses using a random-effects model was conducted to calculate risk ratios (RRs), risk differences (RDs), and mean differences (MDs) 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:

Of 1326 records identified, 15 randomized clinical trials (N = 7122 patients) were included. Most trials assessed adding LAMA vs placebo or LAMA vs LABA to inhaled corticosteroids. Adding LAMA vs placebo to inhaled corticosteroids was associated with a significantly reduced risk of exacerbation requiring systemic corticosteroids (RR, 0.67 [95% CI, 0.48 to 0.92]; RD, -0.02 [95% CI, -0.04 to 0.00]). Compared with adding LABA, adding LAMA to inhaled corticosteroids was not associated with significant improvements in exacerbation risk (RR, 0.87 [95% CI, 0.53 to 1.42]; RD, 0.00 [95% CI, -0.02 to 0.02]), or any other outcomes of interest. Triple therapy was not significantly associated with improved exacerbation risk vs inhaled corticosteroids and LABA (RR, 0.84 [95% CI, 0.57 to 1.22]; RD, -0.01 [95% CI, -0.08 to 0.07]).

Conclusions and Relevance:

In this systematic review and meta-analysis, the use of LAMA compared with placebo as add-on therapy to inhaled corticosteroids was associated with a lower risk of asthma exacerbations; however, the association of LAMA with benefit may not be greater than that with LABA. Triple therapy was not associated with a lower risk of exacerbations.

PMID:
29554174
PMCID:
PMC5876909
DOI:
10.1001/jama.2018.2757
[Indexed for MEDLINE]
Free PMC Article

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