Aclidinium bromide/formoterol fumarate as a treatment for COPD: an update

ABSTRACT

Introduction: Aclidinium/formoterol is a long-acting muscarinic antagonist (LAMA) and long-acting β₂-agonist (LABA) dual bronchodilator used as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). The efficacy of aclidinium/formoterol has been demonstrated consistently in patients with moderate-to-severe COPD versus placebo and monocomponents, with a comparable safety profile.

Areas covered: This review examines recent research findings that expand our understanding of the impact of aclidinium/formoterol on the burden of COPD. Reviewed outcomes include improvements in lung function, respiratory symptoms, health-related quality of life, exercise tolerance, exacerbation rates, and clinically important deteriorations. In addition, the reported cardiovascular safety of aclidinium and current LAMA/LABA treatment recommendations are discussed.

Expert opinion: Aclidinium/formoterol reduces disease burden in patients with COPD, including those that are treatment-naïve, without a significant increase in safety risk compared with monotherapies. Furthermore, evidence supports an improvement in lung function over a 24-hour period with aclidinium/formoterol treatment versus monotherapy and placebo, which may offer an advantage over some once-daily LAMA/LABA combinations. In summary, the recent evidence discussed in this review adds weight to the use of LAMA/LABA combinations as an initial therapy for certain patients newly diagnosed with COPD.

KEYWORDS:

• Aclidinium
• bronchodilators
• COPD
• formoterol
• long-acting β₂-agonist
• long-acting muscarinic antagonist
• maintenance treatment

Article highlights

• Aclidinium/formoterol 400/12 µg twice-daily has a safety profile comparable with its monotherapies and has been shown to improve lung function, health-related quality of life (HRQoL), and respiratory symptoms, as well as reducing exacerbation rates versus monotherapies and/or placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) [16–19].

• Recent evidence has shown that the bronchodilator benefit and improvements in dyspnea in patients receiving aclidinium/formoterol extends to several key patient subgroups versus placebo and its monotherapies, and patients with moderate-to-very severe symptomatic COPD versus placebo, its monotherapies, and tiotropium [27,31].

• Nighttime and early morning symptoms can be problematic in patients with COPD. Aclidinium/formoterol has demonstrated numerical improvements in both nighttime and early morning symptoms versus its monocomponents or tiotropium [27,32,34].

• Improvements in HRQoL scores (both St George’s Respiratory Questionnaire total score and COPD Assessment Test score) from baseline have been demonstrated after 24 weeks of aclidinium/formoterol treatment, which were comparable to its monotherapies and tiotropium in patients with moderate-to-very severe symptomatic COPD [27].

• Aclidinium/formoterol treatment has provided increased exercise endurance time and physical activity while reducing hyperinflation, versus placebo [33].

• Aclidinium/formoterol has been shown to reduce exacerbation rates versus placebo in patients without a history of exacerbations in the previous year, but was comparable to monotherapies in patients with moderate-to-very severe COPD [27,31]. In addition, aclidinium monotherapy reduced exacerbation rates versus placebo irrespective of exacerbation history in the previous year and did not significantly increase the risk of major adverse cardiovascular events or all-cause mortality versus placebo [25,49].

• Several guidelines recommend reserving initial treatment with long-acting muscarinic antagonist (LAMA)/long-acting β₂-agonist (LABA) combinations for patients with more severe symptoms [1,4,65]; however, there is evidence that initial maintenance treatment with LAMA/LABA combination therapy may provide greater benefits than monotherapy for newly diagnosed COPD patients, even in patients with a low exacerbation risk not receiving inhaled corticosteroids [28,54].

• In conclusion, the clinical benefits of aclidinium/formoterol have been demonstrated in key patient subgroups and in patients with moderate-to-very severe COPD. In addition, aclidinium/formoterol improved respiratory symptoms at problematic periods of the day and also increased patient exercise capacity and physical activity versus placebo and/or monotherapies.

Declaration of interest

A D D’Urzo has received research, consulting, and lecturing fees from Almirall, Altana, AstraZeneca, Boehringer Ingelheim (Canada) Ltd, Forest Laboratories, GlaxoSmithKline, KOS Pharmaceuticals, Merck Canada, Methapharm, Novartis Canada/USA, ONO Pharmaceutical Co., Pfizer Canada, Schering-Plough, Sunovian, and SkyePharma.

D Singh has received sponsorship to attend international meetings, honoraria for lecturing or attending advisory boards, and research grants from various pharmaceutical companies, including Apellis, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Genentech, GlaxoSmithKline, Glenmark, Johnson and Johnson, Mundipharma, Novartis, Peptinnovate, Pfizer, Pulmatrix, SkyePharma, Teva, Theravance, and Verona

J F Donohue has received consulting fees from AstraZeneca, GlaxoSmithKline, Novartis, Sunovion, and Theravance. He is a member of the Data Monitoring Committee for AstraZeneca, and Insmed.

K R Chapman has consulted (in the last 3 years) with AstraZeneca, Baxter, Boehringer Ingelheim, CSL Behring, GlaxoSmithKline, Grifols, Kamada, Novartis, Roche, and Teva; has undertaken research funded by Amgen, AstraZeneca, Baxter, Boehringer Ingelheim, CSL Behring, Forest Laboratories, GlaxoSmithKline, Grifols, Mereo BioPharma, Novartis, Regeneron, Roche, and Sanofi; and has participated in continuing medical education activities sponsored in whole or in part by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Merck Frosst, Novartis, and Pfizer. He is also participating in research funded by the Canadian Institutes of Health Research operating grant [entitled ‘Canadian Cohort Obstructive Lung Disease (CanCOLD)’] and holds the GSK-CIHR Research Chair in Respiratory Health Care Delivery at the University Health Network, Toronto, Ontario, Canada.

R A Wise has received personal fees from Aradigm, AstraZeneca, Bonti, Circassia, ContraFect, Denali, Kiniksa, Merck, Mylan, Novartis, Pneuma, Propeller Health, Pulmonx, Regeneron, Roche, Spiration, Sunovion, Syneos, Theravance, and Verona; grants from Pearl Therapeutics; and grants and personal fees from AstraZeneca/MedImmune, Boehringer Ingelheim, and GlaxoSmithKline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was funded by AstraZeneca.