ABSTRACT
Introduction: Bronchodilators, including long-acting muscarinic receptor antagonists (LAMAs), are a mainstay of the pharmacological treatment of chronic obstructive pulmonary disease (COPD). LAMAs act as bronchodilators principally by antagonizing airway smooth muscle cells M3 muscarinic receptors. Aclidinium bromide is a twice-daily LAMA which was developed to improve on the efficacy and/or safety of previous LAMAs.
Area covered: Herein, the authors present the pharmacotherapeutic role of aclidinium in COPD and point out unmet need in this research area. The following aspects are covered: a) the discovery and medicinal chemistry of aclidinium bromide; b) an overview of the market; c) its mechanism of action; d) its pharmacokinetic/pharmacodynamic profile derived from pre-clinical studies; e) the clinical studies which led to its licensing; f) the evidence from meta-analyses; g) the aclidinium/formoterol fixed dose combination for COPD and h) priorities in this area of research.
Expert opinion: Aclidinium bromide has the pharmacological properties, safety and efficacy profile and inhaler characteristics which makes it a valuable therapeutic option for pharmacological management of patients with COPD. Due to its rapid biotransformation into inactive metabolites, aclidinium is potentially one of the safest LAMAs. Further head-to-head randomized clinical trials are required to define efficacy and safety of aclidinium when compared to once-daily LAMAs. The clinical relevance of airway anti-remodeling effects of aclidinium has to be defined.
Article highlights
Due to the importance of cholinergic tone in regulating airway smooth contraction, long-acting muscarinic receptor antagonists (LAMAs) are mainstay bronchodilator treatment for COPD
Aclidinium bromide is a twice-daily LAMA which is approved for maintenance pharmacological treatment of COPD either alone or in a fixed-dose combination with formoterol fumarate, a LABA
The discovery of aclidinium bromide has been stimulated by search for novel, more efficacious and/or more tolerated and safer LAMAs
Aclidinium has an excellent overall and cardiovascular safety profile due to its rapid conversion into inactive metabolites in human plasma
Large randomized clinical trials in COPD patients indicate that aclidinium bromide improves lung function, health related quality of life, dyspnoea and night-time/early morning symptoms
In COPD patients who are uncontrolled by a single bronchodilator, a fixed-dose combination of aclidinium bromide and formoterol fumarate is more efficacious than single monocomponents while reducing the potential risk for side effects due to escalating monotherapies
In vitro and in vivo experimental models have shown anti-remodelling effects of aclidinium whose potential implications for COPD patients warrant further research
Aclidinium is a valuable therapeutic option for pharmacological management of patients with COPD
Gaps in aclidinium research include the lack of comparative prospective studies with other LAMAs, studies with exacerbations as a primary outcome, and data on the potential implications of anti-remodelling effects and twice-daily dosing regimen for COPD management
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Declaration of Interest
M Malerba has received honoraria for speaking and financial support for attending meetings and/or serving on the advisory boards from Chiesi Farmaceutici, Menarini, Mundipharma and Laboratori Guidotti. JB Morjaria has received honoraria for speaking and financial support for attending meetings and/or serving on advisory boards from Wyeth, Chiesi Farmaceutici, Pfizer Inc, Merck Sharp and Dohme, Boehringer Ingelheim, Teva, GlaxoSmithKline/Allen & Hanburys Ltd, Napp Pharmaceutical Group, Almirall, AstraZeneca and Novartis. P Montuschi has also received honoraria for participating on an advisory board from AstraZeneca. 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. One referee wishes to declare that they have undertaken research for and have consulted with AstraZeneca, the current pharmaceutical owner of aclidinium, and to have had similar relationships with companies responsible for competitive LAMAs.