The dose of inhaled corticosteroids in patients with COPD: when less is better

Figures & data

Figure 1 Incidence rates of pneumonia in different studies according to doses of ICS.

Notes: *Comparison between beclometasone/formoterol 640/18 µg formoterol 18 µg. ^†Comparison between fluticasone furoate/umeclidinium/vilanterol vs umeclidinium/vilanterol. ^‡Comparison between FF/vilanterol vs umeclidinium/vilanterol. ^§Comparison between beclometasone/formoterol 320/18 µg formoterol 18 µg. ^¶Both arms of the study were treated with ICS (extrafine BDP/FF/G 400/24/50 vs extrafine BDP/FF 400/24). Only ICS doses approved in COPD are considered.
Abbreviations: BDP, beclomethasone dipropionate; FF, fluticasone furoate; G, glycopyrronium; ICS, inhaled corticosteroids.

Table 1 Characteristics and results of major long-term Phase III double-blind, randomized controlled clinical trials with ICS in patients with COPD

Study, year, reference	No of patients	Length of treatment	Tested products daily dose, µg	ICS daily dose, µg	ICS dose categorya	Annual rate of moderate–severe COPD exacerbations		Incidence or annual rate of pneumonias
						ICS	Control	ICS	Control
Calverley et al, 2007;^Citation15 Crim et al, 2009^Citation76	6,184	3 years	FP/S 1,000/100 vs FP 1,000 vs S 100 vs placebo	FP 1,000	High	FP/S: 0.85; FP: 0.93	S: 0.97; placebo: 1.13	FP/S: 0.088; FP: 0.084 (annual rate)	S: 0.052; placebo: 0.052 (annual rate)
Wedzicha et al, 2008^Citation16	1,323	2 years	FP/S 1,000/100 vs T 18	FP 1,000	High	FP/S: 1.28	T: 1.32	FP/S: 8%	T: 4%
Magnussen et al, 2014^Citation64	2,485	52 weeks	FP/T/S 1,000/18/50 vs T/S 18/50 (FP tapered off over 12 weeks)	FP 1,000	High	FP/T/S: 0.91	T/S: 0.95	FP/T/S: 5.8%	T/S: 5.5%
Wedzicha et al, 2016^Citation75	3,362	52 weeks	FP/S 1,000/100 vs I/G 110/50	FP 1,000	High	FP/S: 1.19	I/G: 0.98	FP/S: 4.8%	I/G: 3.2%
Ferguson et al, 2008^Citation24	782	52 weeks	FP/S 500/100 vs S 100	FP 500	Moderate	FP/S: 1.06	S: 1.53	FP/S: 7%	S: 4%
Anzueto et al, 2009^Citation25	797	52 weeks	FP/S 500/100 vs S 100	FP 500	Moderate	FP/S: 1.10	S: 1.59	FP/S: 7%	S: 2%
Sharafkhaneh et al, 2012^Citation77	1,219	52 weeks	B/FoF 640/18 vs B/FoF 320/18 vs FoF 18b	B 640 or 320b	Moderate, low	B/FoF 640/18: 0.70; B/FoF 320/18: 0.79	FoF: 1.07	B/FoF 640/18: 6.4%; B/FoF 320/18: 4.7%	FoF: 2.7%
Dransfield et al, 2013^Citation26	3,255	52 weeks	FF/V 100/25 vs V 25	FF 100	Moderate	FF/V 100/25: 0.81	V: 1.11	FF/V: 6.3%	V: 3.3%
Lipson et al, 2018^Citation53	10,355	52 weeks	FF/V/U 100/25/62.5 vs FF/V 100/25 vs V/U 25/62.5	FF 100	Moderate	FF/V/U 100/25/62: 0.91; FF/V 100/25: 1.07	V/U 25/62.5: 1.21	FF/V/U: 8%; FF/V: 7%	V/U: 5%
Wedzicha et al, 2014^Citation28	1,186	48 weeks	Extrafine BDP/FoF 400/24 vs FoF 24	BDP 400	Low	BDP/FoF: 0.80	FoF: 1.12	BDP/FoF: 3.8%	FoF: 1.8%
Singh et al, 2016^Citation78	1,368	52 weeks	Extrafine BDP/FoF/G 400/24/50 vs extrafine BDP/FoF 400/24	BDP 400	Low	BDP/FoF/G: 0.45; BDP/FoF: 0.56	NA	BDP/FoF/G: 3%; BDP/FoF: 3%	NA
Vestbo et al, 2017^Citation38	2,691	52 weeks	Extrafine BDP/FoF/G 400/24/50 vs T 18+ extrafine BDP/FoF 400/24 vs T 18	BDP 400	Low	BDP/FoF/G: 0.46; T+BDP/FoF: 0.45	T: 0.57	BDP/FoF/G: 3%; T+BDP/FoF: 2%	T: 2%
Papi et al, 2018^Citation54	1,532	52 weeks	Extrafine BDP/FoF/G 400/24/50 vs I/G 85/43	BDP 400	Low	BDP/FoF/G: 0.50	I/G: 0.59	BDP/FoF/G: 4%	I/G: 4%

Notes:

a Classified according to Bassam M, Mayank V. Steroids in asthma: friend or foe. In: Qian X, editor. Glucocorticoids. New recognition of our familiar friend. IntechOpen; 2012:569–592.⁷⁹ Except fluticasone furoate, which was classified according to the Summary of Product characteristics, based on indicated equivalence to fluticasone propionate.

b Emitted doses.

Abbreviations: B, budesonide; BDP, beclomethasone dipropionate; FF, fluticasone furoate; FoF, formoterol fumarate; FP, fluticasone propionate; G, glycopyrronium; I, indacaterol; ICS, inhaled corticosteroids; S, salmeterol; T, tiotropium; U, umeclidinium; V, vilanterol.

Figure 2 The dose-response curve of ICS.

Note: Reproduced from Kankaanranta et al, 2004,⁵⁶ with the permission of Respiratory Research.
Abbreviation: ICS, inhaled corticosteroids.

Figure 3 Pathophysiological mechanisms involved in systemic adverse effects of ICS in COPD patients.

Abbreviation: ICS, inhaled corticosteroids.

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