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Long-acting muscarinic antagonists + inhaled steroids = long-acting B-agonists + inhaled steroids
Clinical Question
Are long-acting muscarinic antagonists a useful adjunct therapy to inhaled corticosteroids in patients 12 years or older with persistent asthma?
Bottom line
Long-acting muscarinic antagonists (LAMAs) added to inhaled corticosteroids (ICS) is a superior treatment to placebo for improving asthma control in adults and children 12 years or older. LAMA add-on therapy is not superior to long-acting B-agonist (LABA) add-on therapy. The addition of LAMA to patients already receiving LABA + ICS (triple therapy) does not further improve asthma control. 1a
Reference
Study design: Meta-analysis (randomized controlled trials)
Funding: Government
Setting: Various (meta-analysis)
Synopsis
Since 2014 a number of LAMAs (eg, tiotropium/Spiriva, umeclidinium/Incruse, aclidinium/Tudorza) have been marketed for the treatment of asthma. These investigators thoroughly searched multiple sources, including MEDLINE, EMBASE, the Cochrane databases, clinical trial registries, manufacturers' data, and bibliographic references, for studies that compared LAMA therapy with placebo or other controllers as an add-on therapy to ICS in patients at least 12 years old with uncontrolled persistent asthma. No language restrictions were applied. Two reviewers independently evaluated potential studies for inclusion and used a standard scoring tool to assess methodologic quality. Disagreements were resolved by consensus discussion with a third reviewer. A total of 15 randomized controlled trials (N = 7122 patients) met inclusion criteria. Of these, 3 received a high risk of bias score, with the remaining scoring at low risk of bias. Adding a LAMA to ICS compared with adding placebo was significantly associated with a reduced risk of asthma exacerbation requiring systemic corticosteroids (relative risk 0.67; 95% CI 0.48-0.92). There was, however, no significant differences in rescue medication use or quality of life scores between add-on LAMA therapy and add-on placebo. When comparing LAMA to LABA as add-on therapy to ICS, there was no significant difference in risk of asthma exacerbation requiring systemic corticosteroids, rescue medication use, or quality-of-life scores. Triple therapy with LAMA, LABA, and ICS was not superior to LABA plus ICS. Limiting the analysis to only studies with a low risk of bias did not change the results. A formal analysis for publication bias was not possible because of the small number of studies. Formal testing found minimal evidence of significant heterogeneity of results.
Reviewer
David C. Slawson, MD
Professor and Vice Chair of Family Medicine for Education and Scholarship
Atrium Health
Professor of Family Medicine, UNC Chapel Hill
Charlotte, NC
Comments
Good poem
There are convincing data for using Tiotropium Respimat (LAMA) in addition to LABA+ICS in Asthma, but it is not enough for other LAMA. The delivery of medication is very important as well; therefore, device are missing in this study.