Combining Asthma Treatments Works Best for Daily Control and Relieving Attacks, AHRQ-Supported Study Finds

When treating persistent asthma in patients older than 12, using a corticosteroid and a long-acting bronchodilator for both daily asthma control and relief during asthma attacks is more effective than using different medications, according to an AHRQ-supported article inJAMA. Treatment guidelines currently suggest using an inhaled corticosteroid, with or without a long-acting bronchodilator, for daily control, and a different medication (short-acting beta-agonist, albuterol) for rescue relief. Researchers found that using the same combination therapy for both asthma control and for relief resulted in significantly fewer asthma attacks, hospitalizations and emergency room visits. Differences in harms were not evaluated, however. The findings are based on a new AHRQ-supported evidence review, Intermittent Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists for Asthma.

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

Diana M. Sobieraj, PharmD¹; William L. Baker, PharmD¹; Elaine Nguyen, PharmD, MPH¹; et alErin R. Weeda, PharmD¹; Craig I. Coleman, PharmD¹; C. Michael White, PharmD¹; Stephen C. Lazarus, MD²; Kathryn V. Blake, PharmD³; Jason E. Lang, MD, MPH⁴

Author Affiliations Article Information

JAMA. Published online March 19, 2018. doi:10.1001/jama.2018.2757

Key Points

Question What is the efficacy associated with long-acting muscarinic antagonists (LAMAs) as add-on therapy to inhaled corticosteroids in patients with uncontrolled, persistent asthma?

Findings In this meta-analysis that included 15 randomized clinical trials with 7122 participants 12 years or older with uncontrolled, persistent asthma, LAMA vs placebo as an add-on therapy to inhaled corticosteroids was associated with a lower risk of exacerbations requiring systemic corticosteroids (risk difference, −1.8).

Meaning LAMA use was associated with better clinical outcomes than placebo in patients with uncontrolled, persistent asthma.

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.