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Review
. 2018 Dec 12:13:3971-3981.
doi: 10.2147/COPD.S185975. eCollection 2018.

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

Lowie Vanfleteren  1   2   3 , Leonardo M Fabbri  1   4 , Alberto Papi  4 , Stefano Petruzzelli  5 , Bartolome Celli  6
Affiliations
Review

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

Lowie Vanfleteren et al. Int J Chron Obstruct Pulmon Dis. .

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: adrenergic β2 receptor agonists; chronic obstructive; exacerbations; glucocorticoids; muscarinic antagonists; pulmonary disease; review; safety.

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Conflict of interest statement

Disclosure LV reports grants and personal fees from AstraZeneca, grants from Philips, and Fisher and Paykel, and personal fees from Chiesi, GSK, Pulmonx, Menarini, and Boehringer-Ingelheim, all outside the submitted work. LMF reports grants, personal fees, and nonfinancial support from Boehringer-Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Merck Sharp & Dohme, Takeda, AstraZeneca, Novartis, Menarini, Laboratori Guidotti, and Almirall, personal fees and nonfinancial support from Pearl Therapeutics, Mundipharma, and Boston Scientific, personal fees from Kyorin, Bayer, and Zambon, and grants from Pfizer, Dompè, Malesci, Alfasigma, and Vree Health Italia, all outside the submitted work. AP reports grants, personal fees, nonfinancial support, advisory board membership and consultancy work from Chiesi, AstraZeneca, GlaxoSmithKline, Boehringer-Ingelheim, Mundipharma, and TEVA, personal fees and nonfinancial support from Menarini, Novartis, and Zambon, and grants from Sanofi, all outside the submitted work. SP is employed by Chiesi, the sponsor of TRILOGY, TRINITY, and TRIBUTE. BC reports grants to the Division of Pulmonary and Critical Care from AstraZeneca, and that he is a consultant for GlaxoSmithKline, Boehringer-Ingelheim, AstraZeneca, Novartis, Pulmonix, Chiesi, and Menarini, all outside the submitted work. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
The overall benefit/risk ratio (ie, exacerbations/pneumonia) in the TRIBUTE study. Note: Reproduced with permission from Scuri M, Singh D, Fabbri LM, et al. Risk of pneumonia and exacerbations with single inhaler extrafine triple therapy compared to indacaterol/glycopyrronium: post-hoc analysis of the TRIBUTE study. Am J Respir Crit Care Med. 2018;197:A3030. Abbreviations: BDP/FF/G, beclometasone dipropionate/formoterol fumarate/glycopyrronium; IND/GLY, indacaterol/glycopyrronium.
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