Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal

• Published in: International journal of chronic obstructive pulmonary disease Vol. 13; pp. 3971 - 3981
• Main Authors: Vanfleteren, Lowie, Fabbri, Leonardo M, Papi, Alberto, Petruzzelli, Stefano, Celli, Bartolome
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2018; Dove Medical Press Ltd; Dove Medical Press
• Subjects: 2018; Administration, Inhalation; Adrenal Cortex Hormones - administration & dosage; Adrenal Cortex Hormones - adverse effects; adrenergic beta receptor agonists; adrenergic beta-2 receptor agonists; Adrenergic beta-2 Receptor Agonists - administration & dosage; Adrenergic beta-2 Receptor Agonists - adverse effects; airway inflammation; am j resp crit care; Asthma; Beclomethasone; beta-agonists; bronchodilator; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - adverse effects; cardiovascular events; Care and treatment; chronic obstructive; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Corticosteroid drugs; Deflation (Economics); Development and progression; double-blind; Drug Combinations; Dyspnea; Evidence-Based Medicine; exacerbations; fluticasone propionate/salmeterol; Formoterol; Glucocorticoids; Humans; inhaled corticosteroids; Inhalers; Lung - drug effects; Lung - physiopathology; Lung diseases; Lungmedicin och allergi; Mortality; Muscarinic antagonists; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - adverse effects; obstructive pulmonary-disease; parallel-group; Pneumonia; pulmonary disease; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Recovery of Function; Respiratory Medicine and Allergy; Respiratory System; Respiratory system agents; Review; Risk Factors; safety; Severity of Illness Index; Steroids; Steroids (Organic compounds); therapy; Tiotropium; Treatment Outcome; uri m; v197; Vilanterol; pulmonary disease; exacerbations; review; safety; chronic obstructive; muscarinic antagonists; glucocorticoids; adrenergic β2 receptor agonists
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/copd.s185975

Recently, two "fixed triple" single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β
-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) have become available for patients with COPD. This review presents the clinical evidence that led to the approval of these triple therapies, discusses the role of ICS in patients with COPD, and presents data on the relative efficacy of "fixed triple" (ICS/LAMA/LABA) therapy vs LAMA, ICS/LABA, and LAMA/LABA combinations, and summarizes studies in which ICS/LABAs were combined with LAMAs to form "open triple" combinations. Of the five main fixed triple studies completed so far, three evaluated the efficacy and safety of an extrafine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium; the other two studies evaluated fluticasone furoate, vilanterol, and umeclidinium. Overall, compared to LAMA, ICS/LABA, or LAMA/LABA, triple therapy decreased the risk of exacerbations and improved lung function and health status, with a favorable benefit-to-harm ratio. Furthermore, triple therapy showed a promising signal in terms of improved survival. The evidence suggests that triple therapy is the most effective treatment in moderate/severe symptomatic patients with COPD at risk of exacerbations, with marginal if any risk of side effects including pneumonia. Ongoing studies are examining the role of triple therapy in less severe symptomatic patients with COPD and asthma-COPD overlap.