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

Abstract

Lowie Vanfleteren,1–3 Leonardo M Fabbri,1,4 Alberto Papi,4 Stefano Petruzzelli,5 Bartolome Celli6 1COPD Center, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden; 2CIRO, Horn, the Netherlands; 3Department of Respiratory Medicine, Maastricht University Medical Hospital, Maastricht, the Netherlands; 4Section of Cardiorespiratory and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; 5Global Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy; 6Division of Pulmonary and Critical Care, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Recently, two “fixed triple” single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β2-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. Keywords: muscarinic antagonists, adrenergic β2 receptor agonists, glucocorticoids, pulmonary disease, chronic obstructive, review, exacerbations, safety

Keywords

• Muscarinic antagonists
• adrenergic beta-2 receptor agonists
• glucocorticoids
• pulmonary disease
• chronic obstructive
• review
• exacerbations
• safety