Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus addition of long-acting beta2-agonists (LABA) for adults with asthma

• Published in: Cochrane database of systematic reviews 2015-06, Vol.2015 (6), p.CD011438
• Main Authors: Kew, Kayleigh M, Evans, David J W, Allison, Debbie E, Boyter, Anne C
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adrenal Cortex Hormones - administration & dosage; Adrenergic beta-2 Receptor Agonists - administration & dosage; Adult; Asthma - drug therapy; Double-Blind Method; Drug Therapy, Combination - methods; Female; Humans; Male; Medicine General & Introductory Medical Sciences; Middle Aged; Muscarinic Antagonists - administration & dosage; Quality of Life; Randomized Controlled Trials as Topic; Salmeterol Xinafoate - administration & dosage; Tiotropium Bromide - administration & dosage
• ISSN: 1469-493X; 1469-493X
• DOI: 10.1002/14651858.CD011438.pub2

Poorly controlled asthma and preventable exacerbations place a significant strain on healthcare, often requiring additional medications, hospital stays or treatment in the emergency department.Long-acting beta2-agonists (LABA) are the preferred add-on treatment for adults with asthma whose symptoms are not well controlled on inhaled corticosteroids (ICS), but have important safety concerns in asthma. Long-acting muscarinic antagonists (LAMA) have confirmed efficacy in chronic obstructive pulmonary disease and are now being considered as an alternative add-on therapy for people with uncontrolled asthma. To assess the efficacy and safety of adding a LAMA to ICS compared with adding a LABA for adults whose asthma is not well controlled on ICS alone. We searched the Cochrane Airways Group's Specialised Register (CAGR) from inception to April 2015, and imposed no restriction on language of publication. We searched additional resources to pick up unpublished studies, including ClinicalTrials.gov, World Health Organization trials portal, reference lists of primary studies and existing reviews, and manufacturers' trial registries. The most recent search was conducted in April 2015. We searched for parallel and cross-over RCTs in which adults whose asthma was not well controlled with ICS alone were randomised to receive LAMA add-on or LABA add-on for at least 12 weeks. Two review authors independently screened the electronic and additional searches and extracted data from study reports. We used Covidence for duplicate screening, extraction of study characteristics and numerical data, and risk of bias ratings.The pre-specified primary outcomes were exacerbations requiring oral corticosteroids (OCS), quality of life and serious adverse events. We included eight studies meeting the inclusion criteria, but four double-blind, double-dummy studies of around 2000 people dominated the analyses. These four trials were between 14 and 24 weeks long, all comparing tiotropium (usually Respimat) with salmeterol on top of medium doses of ICS.Studies reporting exacerbations requiring OCS showed no difference between the two add-ons, but our confidence in the effect was low due to inconsistency between studies and because the confidence intervals (CI) included significant benefit of either treatment (odds ratio (OR) 1.05, 95% CI 0.50 to 2.18; 1753 participants; 3 studies); three more people per 1000 might have an exacerbation on LAMA, but the CIs ranged from 29 fewer to 61 more. Im