Addressing unmet needs in the treatment of COPD

Abstract

The burden of chronic obstructive pulmonary disease (COPD) is considerable, both socially and economically. Central to COPD management is the use of long-acting bronchodilators, which provide patients with optimal bronchodilation and improvements in symptoms. The once-daily, long-acting β2-agonist indacaterol, the long-acting muscarinic antagonist glycopyrronium, and the indacaterol/glycopyrronium fixed-dose combination QVA149 have all been shown to significantly improve lung function and patient-reported outcomes. The ability to take medication appropriately is important. Easy to use, low resistance devices may help patients take their medication and achieve good drug deposition. There is a need to optimise COPD management by treating the right patients with the right therapy at the right time during the course of their disease. Herein, we present a view on the current COPD management landscape and current unmet needs, and look to the future of COPD treatment and how patient care can be optimised.

Figure 1.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification based on symptom and risk evaluation. a) GOLD model of symptom/risk evaluation of chronic obstructive pulmonary disease (COPD) and recommendations for the initial pharmacological treatment. In evaluating risk, the highest risk according to GOLD grade or exacerbation history should be selected. GOLD 1: forced expiratory volume in 1 s (FEV₁) ≥80% predicted; GOLD 2: FEV₁ 50 – <80% pred; GOLD 3: FEV₁ 30 – <50% pred; GOLD 4: FEV₁ <30% pred. The recommended first-choice treatments and alternative treatment choices for each GOLD group (in alphabetical order) are as follows. A: short-acting β₂-agonist (SABA) or short-acting muscarinic antagonist (SAMA) as needed; long-acting β₂-agonist (LABA) or long-acting muscarinic antagonist (LAMA) or SABA + SAMA. B: LABA or LAMA; LABA + LAMA. C: inhaled corticosteroid (ICS) + LABA or LAMA; LABA + LAMA, LABA + phosphodiesterase-4 (PDE4) inhibitor or LAMA and PDE4 inhibitor. D: ICS + LABA and/or LAMA; ICS + LABA + PDE4 inhibitor or LABA + LAMA or LAMA + PDE4 inhibitor. Other possible treatments are not shown but may be used alone or in combination with first or alternative choices. CAT: COPD Assessment Test; mMRC: modified Medical Research Council. Reproduced from [1] with permission from the publisher. b) The categorisation of patients in GOLD groups C and D based on FEV₁, history of exacerbations or both determinants. ECLIPSE: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints. Reproduced from [62] with permission from the publisher.

Figure 2.

Direct and indirect relaxation of smooth muscle: mechanisms of action of β₂-agonists and muscarinic antagonists. CNS: central nervous system; ACh: acetylcholine; β₂-AR: β₂-adrenergic receptor; M_x: muscarinic receptor type x; G_s: stimulatory G-protein; AC: adenylyl cyclase; PK: protein kinase. Reproduced from [78] with permission from the publisher.

Figure 3.

Serial spirometry on week 26 in the SHINE study. Serial spirometry was conducted in a subset of 294 patients. n: number per treatment group in the serial spirometry subset of the full analysis set; FEV₁: forced expiratory volume in 1 s. Reproduced from [80] with permission from the publisher.

Figure 4.

Annualised rate of chronic obstructive pulmonary disease (COPD) exacerbations over 64–76 weeks in the SPARK study by treatment group. Data are presented as rate reduction (95% CI). ^#: p=0.0052; ^¶: p=0.0072; ⁺: p=0.096; ^§: p=0.038; ^ƒ: p=0.36; ^##: p=0.18; ^¶¶: p=0.0017; ⁺⁺_: p=0.0012. Reproduced from [84] with permission from the publisher.