Current appraisal of single inhaler triple therapy in COPD

Figures & data

Figure 1 Schematic to show effects of inhaled corticosteroid (ICS) moiety of single triple inhaler therapy in COPD.

Notes: (A, B) The benefit is shown as attenuation of bronchial mucosal eosinophilic inflammation resulting in reduced exacerbations; (B, C) risk depicted as impaired mucociliary function with mucus retention and altered microbiome following initial viral infection, along with prolonged bronchial/alveolar ICS retention and resulting local immunosuppression, in turn producing consolidation (pneumonia).

Table 1 Key trials of single triple inhaler ICS/LABA/LAMA vs dual inhalers as either ICS/LABA or LABA/LAMA

Study	Treatments	Exacerbation rate/year	Difference/year	% difference	Time to treat (years)
IMPACT*	ICS/LABA/LAMA (n=4,151) vs ICS/LABA (n=4,134)	0.91 vs 1.07	0.16	15	6.25
IMPACT*	ICS/LABA/LAMA (n=4,151) vs LABA/LAMA (n=2,070)	0.91 vs 1.21	0.30	25	3.33
IMPACT*	ICS/LABA (n=4,134) vs LABA/LAMA (n=2,070)	1.07 vs 1.21	0.14	12	7.14
TRIBUTE*	ICS/LABA/LAMA (n=764) vs LAMA/LABA (n=768)	0.50 vs 0.59	0.09	15	11.11
TRILOGY	ICS/LABA/LAMA (n=687) vs ICS/LABA (n=680)	0.41 vs 0.53	0.12	23	8.33
FULFIL	ICS/LABA/LAMA (n=911) vs ICS/LABA (n=899)	0.22 vs 0.34	0.12	35	8.33
KRONOS	ICS/LABA/LAMA (640) vs LABA/LAMA (627)	0.46 vs 0.95	0.49	52	2.04
KRONOS	ICS/LABA/LAMA (640) vs ICS/LABA (316)	0.46 vs 0.56	0.10	18	10.0
KRONOS	ICS/LABA (316) vs LABA/LAMA (637)	0.56 vs 0.95	0.39	41	2.56

Notes: Data for each trial are shown as number of patients, moderate–severe exacerbation rate, absolute difference, percent relative reduction and time to treat (ie, number of years on treatment required to reduce one exacerbation in an average patient). Key trials include: IMPACT,² TRIBUTE,³ FULFIL,¹³ TRILOGY,¹⁵ KRONOS.²⁶ Asterisk denotes exacerbations were the primary end point.

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LAMA, long-acting muscarinic antagonist.

Figure 2 Duration of lung retention with inhaled corticosteroids due to relative lipophilicity, which in turn determines pneumonia risk in COPD.

Note: Fluticasone furoate (FF), fluticasone propionate (FP), budesonide (BUD), and beclometasone dipropionate (BDP: via its active metabolite 17-BMP) – schematically depicted to reflect their respective kinetic terminal elimination half lives (FF.FP.BUD/BDP).
Abbreviation: 17-BMP, 17-beclometasone monopropionate.

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