Professor Peter Frith, from Flinders University, told the Respiratory Insights Forum that dual therapy with a LABA/LAMA combination exceeds the benefits of monotherapy on all clinically important outcome measures for patients with moderate to severe COPD1.
Their use was supported by both GOLD1 and COPD-X2 guidelines as part of the stepwise management of COPD.
“For patients with moderate to severe COPD, a long-acting bronchodilator – either LABA or LAMA – is indicated as monotherapy as long as the patient is not experiencing multiple exacerbations.”
“If they have continuing symptoms or exacerbations then dual bronchodilator treatment with a LABA/LAMA combination is indicated,” he said.
Recent evidence for combination therapy included findings from the MORACTO 1 and 2 studies3 that tiotropium/olodaterol improved inspiratory capacity compared to either drug as a monotherapy or placebo.
Exercise endurance time also improved significantly with dual therapy vs either monotherapy or placebo in MORACTO 1 and compared with olodaterol or placebo but not tiotropium in MORACTO 2.
“Dual bronchodilation is more effective in encouraging activity over a six week period3,” Professor Frith said.
The findings add to earlier evidence from the SHINE study4 that patients were more likely to be able to perform their daily activities with dual LABA/LAMA bronchodilation than single bronchodilator therapy.
He also highlighted recent research5 that found combining two classes of long-acting bronchodilators appeared to be safe. The study found the addition of a second long-acting bronchodilator did not increase the risk of acute myocardial infarction, stroke or arrhythmia.
However the finding of a modest increase in heart failure in the dual therapy group suggested a need for caution and further investigation, he said.
“Morning breathlessness has a major impact on patients; it is the most troublesome,” he said.
He told the meeting that aclidinium/eformoterol improved 24-hour symptom control including early morning symptom severity and limitation of early morning activities, compared to placebo or either monotherapy6.
The LANTERN study7 showed that a LABA/LAMA combination of indacaterol/glycopyrronium reduced the rate of exacerbations compared to the LABA/ICS combination of salmeterol/fluticasone.
The FLAME study8 also found LABA/LAMA superior to LABA/ICS for preventing exacerbations, and improving lung function and health status.
He said the findings on exacerbations were particularly important given the increased mortality in COPD patients with frequent exacerbations.
More is not necessarily better
Professor Frith said there was limited evidence for any additional benefit on exacerbations from triple therapy.
“The worry is that triple therapy in one inhaler may lead to indiscriminate treatment when there is already a vast overuse of inhaled corticosteroids.”
References
1. The Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2017 report). Available from: http://goldcopd.org
2. Stepwise management of Stable COPD, February 2016. Available from: http://lungfoundation.com.au/health-professionals/ guidelines/copd/stepwise-management-of-stable-copd/ [Accessed March 2017].
3. O’Donnell DE, Casaburi R, Frith P, et al. Effects of combined tiotropium/olodaterol on inspiratory capacity and endurance in COPD. Eur Resp J. 2017;40:1601348.
4. Bateman ED, Ferguson GT, et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Respir J. 2013;42(6):1484-94.
5. Suissa S, Dell’Aniello S & Ernst P. Concurrent use of long-acting bronchodilator in COPD and the risk of adverse cardiovascular events. Eur Resp J. 2017;49:1602245.
6. Bateman ED, Chapman KR et al. Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month, multicenter, randomised studies (ACLIFORM and AUGMENT). Respiratory Research. 2015;16:92.
7. Zhong N, Wang C, et al. LANTERN: a randomised study of QV149 versus salmeterol/fluticasone combination in patients with COPD. Int J COPD. 2015;10:1015-26.
8. Wedzicha JA, Banerji D, et al. Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. NEJM. 2016;374:2222-34.