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

Publication ,  Journal Article
Sobieraj, DM; Baker, WL; Nguyen, E; Weeda, ER; Coleman, CI; White, CM; Lazarus, SC; Blake, KV; Lang, JE
Published in: JAMA
April 10, 2018

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.

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Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

April 10, 2018

Volume

319

Issue

14

Start / End Page

1473 / 1484

Location

United States

Related Subject Headings

  • Risk Assessment
  • Respiratory Function Tests
  • Muscarinic Antagonists
  • Maintenance Chemotherapy
  • Humans
  • General & Internal Medicine
  • Drug Therapy, Combination
  • Bias
  • Asthma
  • Anti-Asthmatic Agents
 

Citation

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Sobieraj, D. M., Baker, W. L., Nguyen, E., Weeda, E. R., Coleman, C. I., White, C. M., … Lang, J. E. (2018). Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma: A Systematic Review and Meta-analysis. JAMA, 319(14), 1473–1484. https://doi.org/10.1001/jama.2018.2757
Sobieraj, Diana M., William L. Baker, Elaine Nguyen, Erin R. Weeda, Craig I. Coleman, C Michael White, Stephen C. Lazarus, Kathryn V. Blake, and Jason E. Lang. “Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma: A Systematic Review and Meta-analysis.JAMA 319, no. 14 (April 10, 2018): 1473–84. https://doi.org/10.1001/jama.2018.2757.
Sobieraj DM, Baker WL, Nguyen E, Weeda ER, Coleman CI, White CM, Lazarus SC, Blake KV, Lang JE. Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma: A Systematic Review and Meta-analysis. JAMA. 2018 Apr 10;319(14):1473–1484.
Journal cover image

Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

April 10, 2018

Volume

319

Issue

14

Start / End Page

1473 / 1484

Location

United States

Related Subject Headings

  • Risk Assessment
  • Respiratory Function Tests
  • Muscarinic Antagonists
  • Maintenance Chemotherapy
  • Humans
  • General & Internal Medicine
  • Drug Therapy, Combination
  • Bias
  • Asthma
  • Anti-Asthmatic Agents