Assessing the clinical value of fast onset and sustained duration of action of long-acting bronchodilators for COPD

Abstract

The long-acting inhaled bronchodilators available for use in chronic obstructive pulmonary disease (COPD) vary in their pharmacological class (β2-adrenergic agonist or antimuscarinic/anticholinergic, alone or combined), durations of action and speed of onset of bronchodilator effect. In the early stages of development of a maintenance bronchodilator, the goals are to identify a molecule with the theoretically 'ideal' profile of fast onset and prolonged duration of action in comparison with existing agents, while minimizing non-specific activity at organs outside the lungs. The move towards increasing duration of bronchodilator action is generally paralleled by improved effects on clinical outcomes, and the advent of more potent agents seems likely to provide an opportunity to reduce overreliance on the use of inhaled corticosteroids in treating COPD. In terms of onset of action, an immediately perceived benefit in reducing dyspnea, although not definitively demonstrated, might prove useful in increasing adherence, which is very poor among patients with COPD. Once-daily administration may also be helpful in this respect. Shared decision-making between patient and physician in the choice of treatment is important in optimizing adherence and, thus, treatment effectiveness.

Efficacy of tiotropium–olodaterol fixed-dose combination in COPD

“…Therefore, if differences were to exist between different LABA/LAMA FDCs, these differences would be small and probably not clinically relevant. Possibly, the currently assessed end points and techniques used to investigate their effects are not sensitive enough to pick up the clinical impact of undeniable differences that prevail between available LAMA/LABA FDCs in terms of pharmacological characteristics of the individual LAMA and LABA components (eg, onset and duration of action, maximum effect and potency, receptor selectivity, lipophilicity, dissociation half-life, serum half-life, and metabolism issues) 7,62,63. Only head-to-head comparisons can solve this issue.…”

Does the Term “Deflators” Reflect More Accurately the Beneficial Effects of Long-acting Bronchodilators in COPD?

“…Based on the nature of the disease, the dominant mechanism of action of long-acting bronchodilators (LABD) on COPD is related to the reduction of hyperinflation. LABAs are again effective on the β 2 -adrenergic receptors of the airway smooth muscle, predominantly in the small airways, whereas long-acting muscarinic antagonists reduce the endogenous cholinergic tone by blocking primarily the M3 muscarinic receptors (8).…”

Indacaterol/Glycopyrronium Combination for COPD

“…We strongly believe the rapid improvement in symptoms could help patients' adherence to treatment, which may be otherwise discouraged by a ''slow'' gradual therapeutic strategy as suggested by guidelines and recommendations [50]. However, also the relative simplicity and convenience of once-daily dosing (compared with multiple daily dosing) may encourage patients' adherence and persistence with their long-term medications [48]. It is clear that at this stage we need a long-term study in real life to confirm that the fast onset and sustained duration of effect are critical to ensure adherence to treatment by patients who are under regular treatment with indacaterol/ glycopyrronium FDC.…”

“…Due to the recognized limitation of [48]. Conversely, it might be of help in patients with suboptimal adherence to treatment, since perceived rapid efficacy could reinforce compliance.…”