Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide

Dave Singh, Massimo Corradi, Monica Spinola, Alberto Papi, Omar S Usmani, Mario Scuri, Stefano Petruzzelli, Jørgen Vestbo, Dave Singh, Massimo Corradi, Monica Spinola, Alberto Papi, Omar S Usmani, Mario Scuri, Stefano Petruzzelli, Jørgen Vestbo

Abstract

The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance. The triple combination therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) has become an option for maintenance treatment of COPD and as a "step-up" therapy from single or double combination treatments. There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations. A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 µg/puff)/formoterol fumarate (6 µg/puff)/glycopyrronium bromide (12.5 µg/puff) has been developed as a hydrofluoroalkane pressurized metered dose inhaler. Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation. This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients.

Keywords: COPD; beclomethasone dipropionate; formoterol fumarate and glycopyrronium bromide; inhaled triple therapy.

Conflict of interest statement

Disclosure DS reports grants and personal fees from Almirall, Astra-Zeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Glenmark, Johnson and Johnson, Merck, NAPP, Novartis, Pfizer, Takeda, Teva, Theravance, and Verona and personal fees from Genentech and Skyepharma. OSU has received industry-academic funding from Boehringer Ingelheim, Chiesi, Edmond Pharma, GlaxoSmithKline, Mundipharma International and has received consultancy or speaker fees from Astra Zeneca, Boehringer Ingelheim, Chiesi, Cipla, Edmond Pharma, GlaxoSmithKline, Napp, Novartis, Mundipharma International, Pearl Therapeutics, Roche, Sandoz, Takeda, UCB, Vectura and Zentiva. JV has received honoraria for consulting and presenting from AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, and Novartis. AP reports grants, personal fees, non-financial support, and others from Chiesi, AstraZeneca, GlaxoSmith-Kline, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Takeda, Mundipharma and TEVA, personal fees and non-financial support from Menarini, Novartis and Zambon, and grants from Sanofi. MC received honoraria for consultancy from Chiesi Farmaceutici SpA. MSp, SP, and MSc are full-time employees of Chiesi Farmaceutici SpA. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
(A) TRILOGY study design. (B) TRINITY study design. Abbreviations: BDP, beclomethasone dipropionate; b.i.d., twice daily; FF, formoterol fumarate; GB, glycopyrronium bromide; o.d., once daily; R, randomization; V, visit; Wk, week.
Figure 2
Figure 2
Moderate/severe exacerbation rate in COPD patients with two or more moderate/severe exacerbations in the year before study entry. Note: TRILOGY (A) and TRINITY (B) studies – ITT population. Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; GB, glycopyrronium bromide; ITT, intention-to-treat.
Figure 3
Figure 3
Moderate/severe COPD exacerbation rate in GOLD B patients. Note: TRILOGY (A) and TRINITY (B) studies – ITT population. Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; GB, glycopyrronium bromide; GOLD, Global Initiative for Obstructive Lung Disease; ITT, intention-to-treat.
Figure 4
Figure 4
Frequency plot considering days in the study versus cumulative number of events (COPD moderate/severe exacerbations and pneumonias) in TRILOGY (A) and TRINITY (B) studies – ITT population. Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; GB, glycopyrronium bromide; ITT, intention-to-treat.

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