Umeclidinium for the treatment of chronic obstructive pulmonary disease

Abstract

Umeclidinium is a novel inhaled long-acting muscarinic receptor antagonist (LAMA) approved for treatment of chronic obstructive pulmonary disease (COPD). It provides a bronchodilation of at least 24 h, is well tolerated and has a safe profile. In this article, we describe its pharmacokinetic and pharmacodynamic characteristics. Moreover, we present a meta-analysis of randomized clinical trials carried out in COPD patients, in which the change of forced expiratory volume in 1 s (FEV₁) induced by umeclidinium has been compared with that elicited by placebo or the active compound tiotropium. The data generated by the pivotal trials indicate that umeclidinium bromide delivered once-daily via the Ellipta™ inhaler is an effective and well-tolerated treatment for COPD. Therefore, it could to be used as an alternative to LAMAs already in the market, although substantial information is still lacking. It is likely that in the future, umeclidinium will be used frequently, mainly in combination with vilanterol, which is a new once-daily long-acting β2-agonist (LABA).

Keywords::

• bronchodilators
• COPD
• Ellipta™ inhaler
• LAMA
• umeclidinium bromide

Financial & competing interests disclosure

M Cazzola is a member of an international advisory board of GSK and a consultant at GSK Italia. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Parasympathetic activity is increased in patients with chronic obstructive pulmonary disease (COPD), and this appears to be the major reversible component of airway obstruction.

• The importance of tiotropium bromide, the only long-acting muscarinic receptor antagonist (LAMA) approved for maintenance therapy in COPD until recently, in the maintenance treatment of COPD has promoted further research to identify new LAMAs.

• Umeclidinium bromide is a potent and competitive antagonist of muscarinic M3 receptors that has been designed as an inhaled once-daily LAMA for use as monotherapy and in combination with the long-acting β2-agonist vilanterol.

• Umeclidinium showed kinetic selectivity for M3 receptors over M2 and dissociation from the M3 muscarinic receptors, which was slower than that of the M2 muscarinic receptors.

• The pharmacokinetic steady state of umiclidinium is achieved after 4–5 half-lives of the drug.

• Umeclidinium is delivered via a novel, single-step activation, multidose, dry powder inhaler for oral inhalation, Ellipta™, which delivers consistent doses within the respirable range over the lifetime of the product.

• The data generated by the pivotal trials indicate that umeclidinium bromide delivered once daily via the Ellipta™ inhaler is an effective and well-tolerated treatment for COPD.

• Additional trials to assess advantages over other LAMAs already in the market are required to allow the place of umeclidinium bromide to be fully elucidated.