Recent advances in COPD disease management with fixed-dose long-acting combination therapies

Abstract

Combinations of two long-acting bronchodilators and long-acting bronchodilators with inhaled corticosteroids (ICS) are recommended therapies in the management of chronic obstructive pulmonary disease (COPD). Three fixed-dose combination products have recently been approved for the treatment of COPD (the long-acting β₂-agonist plus long-acting muscarinic antagonist [LABA/LAMA] combinations glycopyrronium/indacaterol [QVA149] and umeclidinium/vilanterol, and the LABA/ICS fluticasone furoate/vilanterol), with others currently in late-stage development. LABA/LAMA and LABA/ICS combination therapies demonstrate positive effects on both lung function and patient-reported outcomes, with significant improvements observed with LABA/LAMA combinations compared with placebo, each component alone and other comparators in current use. No new safety concerns have been observed with combinations of long-acting bronchodilators. Combinations of two long-acting bronchodilators represent a new and convenient treatment option in COPD. This review summarizes published efficacy and safety data from clinical trials of both LABA/LAMA and novel LABA/ICS combinations in patients with COPD.

Keywords::

• combination therapy
• chronic obstructive pulmonary disease
• exacerbation
• inhaled corticosteroids
• long-acting bronchodilators
• lung function
• patient-reported outcomes

Financial & competing interests disclosure

ED Bateman has served as a consultant to Actelion, ALK-Abelló, Almirall, AstraZeneca, Boehringer Ingelheim, Cephalon, MS Consulting Group; served on advisory boards for Almirall, AstraZeneca, Boehringer Ingelheim, Forest, GlaxoSmithKline, Merck, Napp, Novartis and Takeda; received lecture fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer and Takeda; and his institution has received remuneration for participation in clinical trials sponsored by Actelion, Aeras, Almirall, AstraZeneca, Boehringer Ingelheim, Cephalon, Forest, Genentech, GlaxoSmithKline, Hoffmann-La Roche, Merck, Novartis, Takeda and TEVA. DA Mahler serves as a consultant to Boehringer Ingelheim, Forest, GlaxoSmithKline, Novartis and Sunovion; and serves on advisory boards for Forest, GlaxoSmithKline, Merck, Novartis, Pearl and Sunovion. The Clinical Trials Office at Dartmouth-Hitchcock Medical Center, Hanover, USA, has received grant support from Boehringer Ingelheim, GlaxoSmithKline, Novartis and Sunovion for which DA Mahler was the Principal Investigator. CF Vogelmeier has given presentations at symposia and/or served on scientific advisory boards sponsored by Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Janssen, Mundipharma, Novartis and Takeda. JA Wedzicha has received honoraria for lectures and/or advisory boards from Almirall, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, Novartis and Takeda. F Patalano and D Banerji are employees of Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors were assisted in the preparation of the manuscript by Elizabeth Andrew, a professional medical writer contracted to CircleScience (Tytherington, UK). Writing support was funded by Novartis Pharma AG, Basel, Switzerland.

Key issues

• Monotherapy with long-acting bronchodilators provides improvements in lung function, dyspnea, health-related quality of life, rescue medication use, exercise capacity and exacerbation risk versus placebo.

• Long-acting β₂-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) can be prescribed together in separate inhalers, but this combination is not as widely used as the combination of a LABA with an inhaled corticosteroid (ICS).

• According to the Global Initiative for chronic Obstructive Lung Disease (GOLD) strategy, LABA/ICS combinations are recommended for patients at high risk of exacerbation (in GOLD groups C and D), although studies of prescription patterns suggest they are commonly used in low-risk patients.

• An alternative choice of treatment for patients in groups B to D, according to GOLD, is a combination of long-acting bronchodilators (a LABA plus a LAMA).

• There are a number of new fixed-dose LABA/LAMA and LABA/ICS combinations under investigation, some suitable for once-daily dosing, and considerable data on the efficacy and safety of both therapies in patients with chronic obstructive pulmonary disease are available.

• New LABA/LAMA combinations include glycopyrronium plus indacaterol (QVA149), umeclidinium plus vilanterol, glycopyrrolate plus formoterol, tiotropium plus olodaterol and aclidinium plus formoterol.

• Novel LABA/ICS combinations either currently being evaluated or recently approved for use in chronic obstructive pulmonary disease include fluticasone furoate plus vilanterol, mometasone furoate plus formoterol and beclomethasone plus formoterol.

• LABA/LAMA and LABA/ICS combination therapies demonstrate positive effects on both lung function and patient-reported outcomes.

• Improvements in lung function and symptoms have been observed with LABA/LAMA combinations compared with placebo, LABA and LAMA monotherapies and other comparators in current use.

• Recognition that bronchodilators can be combined with additive efficacy could foreseeably lead to a shift in prescription patterns toward LABA/LAMA and away from LABA/ICS combination therapy, particularly for GOLD group B patients with a high symptom burden and low exacerbation risk.

Notes