Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting β₂-agonist bronchodilators

ABSTRACT

Long-acting inhaled bronchodilator medications are recommended as initial maintenance therapy for many patients with COPD. These medications include long-acting muscarinic antagonists (LAMA) and long-acting β₂-agonists (LABA). Combinations of long-acting bronchodilator agents (LAMA/LABA) and inhaled corticosteroids combined with LABA (ICS/LABA) are also used as initial or follow-up therapy in patients with more severe symptoms or at risk of COPD exacerbations. This review summarizes the position of LAMA/LABA combinations in treatment recommendations, and the evidence supporting their placement relative to LAMA monotherapy and ICS/LABA combination therapy, as well as differences within the LAMA/LABA class. Most studies show that LAMA/LABA treatment leads to greater improvements in lung function and symptoms than LAMA monotherapy or ICS/LABA treatment. There are fewer studies comparing the impact of different medication classes on patients’ risk of exacerbations; however, the available evidence suggests that LAMA/LABA treatment and LAMA monotherapy lead to a similar reduction in exacerbation risk, while the effect of LAMA/LABA compared with ICS/LABA remains unclear. The incidence of adverse events is similar with LAMA/LABA and LAMA alone. There is a lower risk of pneumonia with LAMA/LABA compared with ICS/LABA. This evidence supports the use of LAMA/LABA combinations as an initial maintenance therapy option for symptomatic patients with low exacerbation risk and severe breathlessness or patients with severe symptoms who are at risk of exacerbations, and as follow-up treatment in patients with uncontrolled symptoms or exacerbations on bronchodilator monotherapy.

KEYWORDS:

• COPD
• dual bronchodilators
• GOLD strategy
• LAMA
• LABA
• ICS/LABA
• LAMA/LABA
• FEV₁
• COPD symptoms
• COPD exacerbations

Acknowledgments

We acknowledge the support and contributions of Dr Michael Asmus in the preparation of this manuscript. Medical writing support was provided by Mark Condon, DPhil, of Fishawack Indicia Ltd, UK, and was funded by GlaxoSmithKline (GSK).

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

Dr Skolnik reports personal fees from AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, Janssen Pharmaceuticals, Intarcia, Mylan, GSK, and Merck, and non-financial support from AstraZeneca, Boehringer Ingelheim, and Sanofi, outside the submitted work. Dr Ray and Dr Corbridge are employees of GSK and hold GSK stocks/shares. Dr Brunton has attended advisory boards for AstraZeneca, GSK, and Mylan, and a speakers’ bureau for AstraZeneca. Dr Nguyen and Dr Shrestha report no conflicts of interest.

Additional information

Funding

This review was supported by GSK. Drs Skolnik, Nguyen, Shrestha, and Brunton were not compensated by GSK for their contribution to the concept, design, and writing of this manuscript. The funders had a role in preparation of the manuscript, in the form of providing funding for medical writing support, while the decision to publish was made solely by the authors.