Dual bronchodilator therapy with aclidinium bromide/formoterol fumarate for chronic obstructive pulmonary disease

Abstract

Inhaled bronchodilator therapy is a mainstay of treatment for chronic obstructive pulmonary disease (COPD). Despite the number and types of treatments available, the control of symptoms and exacerbations remains suboptimal, and adherence to, and persistence with, inhaled therapy is generally poor. Results from clinical studies suggest that dual bronchodilator therapy with long-acting muscarinic receptor antagonists (LAMAs) and long-acting β₂ adrenergic receptor agonists (LABAs) may provide additional benefit over LAMA or LABA monotherapy without additive effects on safety and tolerability. Several combinations of a LAMA plus a LABA have recently become available in a single inhaler for maintenance therapy for adults with moderate-to-severe COPD, including aclidinium bromide/formoterol fumarate, glycopyrronium/indacaterol and umeclidinium/vilanterol. Here, we review clinical data demonstrating significant improvements in bronchodilation, 24-h symptoms, and health status with aclidinium/formoterol twice daily, and discuss how this treatment can be implemented in clinical practice as part of a patient-focused approach to disease control.

Keywords:

• aclidinium bromide
• bronchodilation
• chronic obstructive pulmonary disease
• combination therapy
• dyspnea
• formoterol fumarate
• long-acting β2-agonist
• long-acting muscarinic antagonist
• symptoms

Financial & competing interests disclosure

T D’Urzo has received research, consulting and lecturing fees from Forest laboratories, GlaxoSmithKline, Sepracor, Merck Canada, Schering Plough, Novartis Canada/USA, Altana, Boehringer Ingelheim Canada, Methapharm, Pfizer Canada, AstraZeneca, Skye Pharma, Ono Pharma, and Kos Pharmaceuticals. J Donohue has served as consultant to Almirall, AstraZeneca, Boehringer Ingelheim, Dey, Elevation Pharmaceuticals, Forest Laboratories, GlaxoSmithKline, Novartis, Pearl Pharmaceuticals, Pfizer and Sunovion; and has received research grants from Boehringer Ingelheim, GlaxoSmithKline and Novartis. D Price has served on advisory boards for Aerocrine, Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis and Teva. He has consultant arrangements with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Pfizer and Teva. He or his research team has received grants (or grants pending) and support for research in respiratory disease from the following organizations in the last 5 years: UK National Health Service, British Lung Foundation, Aerocrine, AstraZeneca, Boehringer Ingelheim, Chiesi, Eli Lilly, GlaxoSmithKline, Meda, Merck, Mundipharma, Novartis, Orion, Pfizer, Respiratory Effectiveness Group, Takeda, Teva and Zentiva. He has received unrestricted funding for investigator-initiated studies from Aerocrine, AKL Ltd, Almirall, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, Orion, Takeda, Teva and Zentiva. He has received funding for patient enrolment or completion of research from Almirall, Chiesi, Teva and Zentiva. He has received payments for lectures/speaking from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Meda, Merck, Mundipharma, Novartis, Pfizer, Skyepharma, Takeda and Teva; travel/accommodations/meeting expenses from Aerocrine, Boehringer Ingelheim, Mundipharma, Napp, Novartis and Teva; manuscript preparation from Mundipharma and Teva; development of educational materials from GlaxoSmithKline and Novartis. He has patents and shares with AKL Ltd and owns 80% of Research in Real Life Ltd and its subsidiary social enterprise Optimum Patient Care. M Miravitlles has received speaker fees from Almirall, Boehringer Ingelheim, Pfizer, AstraZeneca, Chiesi, Esteve, GlaxoSmithKline, Menarini, Talecris-Grifols, Takeda-Nycomed and Novartis, and consulting fees from Almirall, Boehringer Ingelheim, Cipla, Pfizer, GlaxoSmithKline, Gebro Pharma, MediImmune, Novartis, Talecris-Grifols, Teva and Takeda-Nycomed. E Kerwin has served on advisory boards, speaker panels, or received travel reimbursement with AstraZeneca, Forest Laboratories, Ironwood, Merck, Mylan, Novartis, Pearl, Pfizer, Sanofi Aventis, Sunovion Targacept, and Theravance. He has conducted multicenter clinical research trials for approximately 70 pharmaceutical companies. 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. Medical writing support, funded by AstraZeneca PLC, Barcelona, Spain was provided by Kirsteen Munn of Complete Medical Communications, Macclesfield, UK.

Key issues

• The burden of COPD is expected to increase due to the aging population and increased exposure to risk factors.

• Control of COPD symptoms and exacerbations remains suboptimal, and adherence to inhaled therapy is generally poor.

• Results from clinical studies have suggested that dual bronchodilator therapy with LAMAs and LABAs may provide additional benefit over LAMA or LABA monotherapy without additive effects on safety and tolerability.

• Several combinations of a LAMA plus a LABA are available in a single inhaler for maintenance therapy for adults with moderate-to-severe COPD, including aclidinium bromide/formoterol fumarate, glycopyrronium/indacaterol and umeclidinium/vilanterol.

• Aclidinium/formoterol 400/12 µg, administered twice daily with the breath-actuated MDPI Genuair^TM has demonstrated rapid and sustained bronchodilation in patients with stable COPD.

• Improvements in lung function, 24-h symptoms, including early-morning and nighttime symptoms and health status have been demonstrated in two Phase III trials of aclidinium bromide/formoterol fumarate involving >3,000 patients with moderate-to-severe COPD.

Notes

^aRegistered trademark of AstraZeneca group of companies; for use within the USA as Pressair^® and as Genuair^TM within all other licensed territories.