Long-acting bronchodilators in COPD: where are we now and where are we going?

Abstract

Educational aimsTo discuss fundamental questions relating to the use of bronchodilators that can lead to an optimisation of their utilisation.To describe new bronchodilators that have recently been approved in some countries or are currently undergoing clinical developmentSummaryBronchodilators are central to the treatment of chronic obstructive pulmonary disease (COPD) because they alleviate bronchial obstruction and airflow limitation, reduce hyperinflation, and improve emptying of the lung and exercise performance. For this reason, all guidelines highlight that inhaled bronchodilators are the mainstay of the current management of all stages of COPD.However, there are still fundamental questions regarding their use that require clarification to optimise utilisation of these drugs. It is crucial to address the following questions. Is it appropriate to treat all COPD patients with long-acting bronchodilators? Is it better to start treatment with a β2-agonist or with an anti-muscarinic agent in patients with stable mild/moderate COPD? Is it useful to use a bronchodilator with rapid onset of action? Is it preferable to administer a bronchodilator on a once- or twice-daily basis? Can a second bronchodilator can be introduced for patients with stable COPD (“dual” bronchodilator therapy), and if so when? Are inhaled corticosteroids (ICSs) really useful in COPD patients without chronic bronchitis, since long-lasting bronchodilators may prevent exacerbations even in the absence of an ICS in frequent exacerbators? Finally, is combined therapy really useful in non-frequent exacerbators?Due to the the central role of bronchodilators in the treatment of COPD, there is still considerable interest in finding novel classes of bronchodilator drugs. However, new classes of bronchodilators have proved difficult to develop because either new emerging targets are not really important and/or it is difficult to find substances capable of interacting with them. As a consequence, many research groups have sought to improve the existing classes of bronchodilators.

A Network Meta-Analysis of Long-Acting Muscarinic Antagonist (LAMA) and Long-Acting β2-Agonist (LABA) Combinations in COPD

“…Bronchodilators, particularly long-acting muscarinic antagonists (LAMAs) and long-acting b 2 -agonists (LABAs), have become the mainstay of pharmacological therapy for chronic obstructive pulmonary disease (COPD) [1][2][3]. Despite the well-demonstrated utility of LABAs [4][5][6][7] and LAMAs [8][9][10][11] as maintenance therapy, a high number of patients with moderate or severe COPD receiving LABA or LAMA monotherapy can fail to achieve adequate control of symptoms [12].…”

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

“…Inhaled long-acting bronchodilators are used for the treatment of patients with moderate and more severe COPD (14), and now, agents are available for once-daily administration. Indacaterol is an inhaled, once-daily, ultra-long-acting β2-agonist (15).…”

Clinical Trial Risk in Chronic Obstructive Pulmonary Disease: The Effects of Drug Class and Inclusion Criteria

“…However, although this minimizes the risk of clinical failure and losing financial investments from a clinical trial risk perspective, the launch of these ‘me too' products based on well-known mechanisms may in turn encounter significant commercial challenges in the marketplace. Overall, COPD has traditionally been an area where manufacturers have looked to improve on drugs with well-known mechanisms of action and where new therapies may only be slight improvements over their predecessors [31,32]. Thus, products not first to market in their respective drug classes may encounter significant commercial hurdles in differentiating from competitors or changing clinical practice in an already crowded marketplace.…”