Intermittent Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists for Asthma

SYSTEMATIC REVIEW

March 19, 2018

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Key Messages

Purpose of Review

To assess the efficacy of intermittent inhaled corticosteroids in different populations of patients with asthma and to assess whether adding long-acting muscarinic antagonists improves outcomes for patients with uncontrolled, persistent asthma.

Key Messages

In children less than 5 years old with recurrent wheezing, intermittent use of inhaled corticosteroids during an upper respiratory tract infection decreases asthma exacerbations
In patients 12 years and older with persistent asthma:
- using inhaled corticosteroids intermittently may be as effective as using them as a controller medication
- using inhaled corticosteroids and long-acting beta-agonists together as controller and quick relief therapy reduces asthma exacerbations compared to using inhaled corticosteroids alone or with long-acting beta agonist as a controller
In patients 12 years and older with uncontrolled, persistent asthma, adding long-acting muscarinic antagonist to:
- inhaled corticosteroids reduces exacerbations and improves lung function
- inhaled corticosteroids and long-acting beta-agonist controllers improves asthma control and lung function

Structured Abstract

Objective. To assess efficacy of intermittent inhaled corticosteroid (ICS) therapy in different populations (0 to 4 years old with recurrent wheezing, 5 years and older with persistent asthma, with or without long-acting beta agonist [LABA]), and to assess efficacy of added long-acting muscarinic antagonist (LAMA) in patients 12 years and older with uncontrolled, persistent asthma.

Data sources. MEDLINE®, Embase®, Cochrane Central, and Cochrane Database of Systematic Reviews bibliographic databases from earliest date through March 23, 2017; hand searches of references of relevant studies; www.clinicaltrials.govand the International Controlled Trials Registry Platform.

Review methods. Two investigators screened abstracts of identified references for eligibility and subsequently reviewed full-text files. We abstracted data, performed meta-analyses when appropriate, assessed the risk of bias of each individual study, and graded the strength of evidence for each comparison and outcome. Outcomes for which data were extracted included exacerbations, mortality, asthma control composite scores, spirometry, asthma-specific quality of life, and rescue medication use.

Results. We included 56 unique studies (54 randomized controlled trials, 2 observational studies) in this review. Compared to rescue short-acting beta-agonist (SABA) use, adding intermittent ICS reduces the risk of exacerbation requiring oral steroids and improves caregiver quality of life in children less than 5 years old with recurrent wheezing in the setting of a respiratory tract infection (RTI). In patients 12 years and older with persistent asthma, differences in intermittent ICS versus controller use of ICS were not detected, although few studies provided evidence, leading to primarily low strength of evidence ratings. Using ICS and LABA as both a controller and quick relief therapy reduced the risk of exacerbations and improved symptom control in patients 12 years and older compared to ICS controller (with or without LABA). Data in patients 4 to 11 years old suggest lower risk of exacerbations with ICS and LABA controller and quick relief use, but with a lower strength of evidence than in the older population. In patients 12 years and older with uncontrolled, persistent asthma, LAMA versus placebo as add-on to ICS reduces the risk of exacerbations requiring systemic corticosteroids and improves lung function measure through spirometry. Current evidence does not suggest that a difference exists in the efficacy of LAMA versus LABA as add-on to ICS. Triple therapy of ICS, LAMA, and LABA improves lung function measured through spirometry, although the risk of exacerbation was not different versus ICS and LABA.

Conclusions. Intermittent ICS added to SABA during an RTI provides benefit to patients less than 5 years of age with recurrent wheezing. In patients 12 years and older with persistent asthma, differences in intermittent ICS versus controller use of ICS were not detected, although few studies provided evidence for this question. In patients 12 years and older with persistent asthma, using ICS and LABA as both a controller and quick relief therapy may be more effective at preventing exacerbations than ICS controller (with or without LABA). LAMA is effective in the management of uncontrolled, persistent asthma in patients 12 years of age and older, and current evidence does not suggest a difference between LAMA and LABA as add-on to ICS.

Journal Publications

Sobieraj DM, Baker WL, Nguyen E, et al. Association of inhaled corticosteroids and long-acting muscarinic antagonists with asthma control in patients with uncontrolled, persistent asthma: a systematic review and meta-analysis[link is external][published online March 19, 2018]. JAMA. doi:10.1001/jama.2018.2757.

Sobieraj DM, Weeda ER, Nguyen E, et al. Association of inhaled corticosteroids and long-acting β-agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma: a systematic review and meta-analysis[link is external] [published online March 19, 2018]. JAMA. doi: 10.1001/jama.2018.2769.

Citation

Suggested citation: Sobieraj DM, Baker WL, Weeda ER, Nguyen E, Coleman CI, White CM, Lazarus SC, Blake KV, Lang JE. Intermittent Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists for Asthma. Comparative Effectiveness Review No. 194. (Prepared by the University of Connecticut Evidence-based Practice Center under Contract No. 290-2015-00012-I.) AHRQ Publication No. 17(18)-EHC027-EF. Rockville, MD: Agency for Healthcare Research and Quality; March 2018. Posted final reports are located on the Effective Health Care Program search page. DOI: https://doi.org/10.23970/AHRQEPCCER194. [link is external]