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

作者：Sobieraj Diana M^*; Baker William L; Nguyen Elaine; Weeda Erin R; Coleman Craig I; White C Michael; Lazarus Stephen C; Blake Kathryn V; Lang Jason E

来源：Journal of the American Medical Association, 2018, 319(14): 1473-1484.

DOI：10.1001/jama.2018.2757

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 beta-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 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 (RR5), risk differences (RD5), and mean differences (MDs) with corresponding 95% Cls. 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% Cl, 0.48 to 0.92]; RD,-0.02 [95% Cl,-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% Cl, 0.53 to 142]; RD, 0.00 [95% Cl,-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% Cl, 037 to 1.22]; RD,-0.01 [95% Cl,-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.

• 出版日期2018-4-10