Efficacy and safety of triple combination therapy for treating chronic obstructive pulmonary disease: an expert review

ABSTRACT

Introduction: The current recommendations of chronic obstructive pulmonary disease (COPD) suggest to escalate from inhaled corticosteroid/long-acting β₂-adrenoceptor agonist (ICS/LABA) treatment to triple therapy in patients experiencing persistent breathlessness, exercise limitation, or exacerbation. The addition of an ICS to LABA/long-acting muscarinic antagonist (LAMA) combination is recommended for frequently exacerbating patients with high levels of blood eosinophils. Nowadays, three triple therapies have been approved as fixed-dose combinations (FDCs) for the treatment of COPD: beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FOR/GLY), fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), and budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR).

Areas covered: This narrative review evaluates the efficacy and safety profile of triple FDC therapy for the treatment of COPD, by evaluating the data originating from pivotal randomized-controlled trials (RCTs).

Expert opinion: The currently approved triple FDCs exert a protective effect against the risk of COPD exacerbation compared to ICS/LABA and LABA/LAMA, with some concerns regarding the risk of pneumonia for some specific FDCs. Since the assessed RCTs were characterized by important confounders, the obtained results should be interpreted with caution. Indeed, FDCs provide advantages in terms of improved adherence to treatment and lower errors in COPD management; however, direct head-to-head comparisons are needed to establish real differences between the currently approved triple FDCs.

KEYWORDS:

• Chronic obstructive pulmonary disease
• fixed-dose combinations
• inhaled corticosteroids
• long-acting β₂-adrenoceptor agonists
• long-acting muscarinic receptor antagonists
• triple therapy

Article highlights

• Triple FDCs are effective to treat COPD patients, especially those with high levels of blood eosinophils.

• No cardiovascular safety matters are related with the use of triple FDCs in COPD patients.

• Triple FDCs may increase the risk of pneumonia in a dose-dependent and compound-related manner.

• Direct head-to-head comparisons are needed to establish the real differences in the efficacy and safety between the currently approved triple FDCs.

This box summarizes key points contained in the article.

Declaration of interest

L Calzetta has participated as an advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis, received non-financial support from AstraZeneca, a research grant partially funded by Chiesi Farmaceutici, Boehringer Ingelheim, Novartis, and Almirall, and is or has been a consultant to ABC Farmaceutici, Recipharm, Zambon, Verona Pharma and Ockham Biotech. His department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis and Zambon. M Cazzola has participated as a faculty member, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, Novartis, Pfizer, Verona Pharma, and Zambon, and is or has been a consultant to ABC Farmaceutici, AstraZeneca, Chiesi Farmaceutici, Edmond Pharma, Lallemand, Novartis, Ockham Biotech, Verona Pharma, and Zambon. His department was funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon. P Rogliani has participated as a lecturer and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma and Novartis. Her department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis, and Zambon. 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.

Reviewer disclosures

Over the past 5 years, one referee has conducted multi-center clinical trials for 3M, Abbott, AbbVie, Adare Pharmaceuticals, ALK-Abello, Amgen, Amneal, Amphastar, AnaptysBio AOBiome, Arcutis, AstraZeneca, Avillion, Biota, Boehringer Ingelheim, Cara Therapeutics, Cephalon (Teva), Chiesi Farmaceutici, Cipla, Circassia, Daiichi Sankyo, Dermira, DS Biopharma, Forest Laboratories (AstraZeneca), Galderma, Genentech (Roche), GlaxoSmithKline (GlaxoWellcome), Glenmark, Gossamer, Incyte, Intarcia, Johnson & Johnson, Kowa, Knopp Biosciences, Leo Pharma, Lupin, Merck & Co., Moderna, Mylan, Novartis, Pearl Therapeutics, Pfizer Inc, Romark, resTORbio, Roche, Sanofi, Stallergenes, Sunovion, Teva, Theravance, and Vanda. Another referee declares that they are a former employee of and current consultant for GlaxoSmithKline.

Additional information

Funding

This manuscript was not funded.