Overuse of inhaled corticosteroids in COPD: five questions for withdrawal in daily practice

Figures & data

Table

• ICS monotherapy is not recommended • ICS-containing regimens are not recommended as initial maintenance treatment for COPD patients, except in some patients, such as in those with a history and/or findings suggestive of asthma–COPD overlap where it may be a first choice • LABA/ICS may be an alternative to LAMA/LABA therapy in frequent exacerbators with few symptoms, but it is not preferred due to the risk of pneumonia (Group C) • Symptomatic patients with a history of frequent exacerbations (Group D) can be raised to an ICS-containing triple treatment if their symptoms persist or if they have further exacerbations despite optimal bronchodilation

Notes: Data from GOLD. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2017 Report). Global Initiative for Chronic Obstructive Lung Disease, Inc.; 2017.²⁴

Abbreviations: ICS, inhaled corticosteroid; GOLD, Global Initiative for Chronic Obstructive Lung Disease; LABA, long-acting β2-adrenoreceptor agonist; LAMA, long-acting muscarinic receptor antagonist.

Figure 1 Algorithm for withdrawal of ICS in symptomatic patients with COPD.^a

Note: ^aIf asthma–COPD overlap, continue ICS therapy and monitor for potential ICS-related adverse events; percentages of patients are based on the DACCORD population.⁵⁵
Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting β2-adrenoreceptor agonists; LAMA, long-acting muscarinic receptor antagonist.

Table 1 Overview of ICS withdrawal studies

Study	Publication year	Disease stage	Exacerbation risk	Pretreatment	n	Run-in	Treatment group		Concomitant bronchodilator treatment	Run-in	Exacerbation risk (ICS-discontinued group vs ICS-continued group)
							ICS-discontinued group	ICS-continued group
Randomized controlled trials
Magnussen et al^Citation16 (WISDOM)	2014	Severe and very severe COPD (mean FEV1% predicted: 34.2±11)	≥1	70% ICS; 65% LABA; 47% LAMA	2,485	6 weeks TIO 18 µg od+SAL 50 µg bid+FP 500 µg bid	TIO 18 µg od+SAL 50 µg bid+FP from 500 µg bid to 0 µg (PBO) in 3 steps of 6 weeks	TIO 18 µg od+SAL 50 µg bid+FP 500 µg bid	LAMA+LABA	12 months	NS
Rossi et al^Citation40 (INSTEAD)	2014	Moderate COPD (mean FEV1% predicted: 64.1±8.18)	0	≥3 months SAL/fluticasone propionate 50/500 µg bid	581	2 weeks SAL/FP 50/500 µg bid	IND 150 mg od	SAL/FP 50/500 µg bid	LABA	6 months	NS
Choudhury et al^Citation41 (WISP)	2007	Primary care population: FEV1% predicted: <80 (mean: 54.1)		ICS for at least 6 months (median 8 years); 33% LABA	260	2 weeks on regular ICS	PBO	FP 500 µg bid		12 months	Increased risk
Wouters et al^Citation42 (COSMIC)	2005	Moderate and severe COPD (mean FEV1% predicted: 47.8)	≥2	22% ICS; 3% LABA; 63% LABA/ICS	373	3 months SAL/FP 50/500 µg bid	SAL 50 µg bid	SAL/FP 50/500 µg bid	LABA	12 months	Increased risk
van der Valk et al^Citation43 (COPE)	2002	Moderate to very severe COPD (mean FEV1% predicted: 56.8)	Mean 1.3	86% ICS ≥6 months; 46% LABA	244	4 months FP 500 µg bid	PBO	FP 500 µg bid	50% on LABA	6 months	Increased risk
O’Brien et al^Citation44	2001	Severe COPD		Regular ICS use	24		PBO	BDP 336 µg/day	None	6 weeks cross-over	NS (underpowered)
Observational trials
Vogelmeier et al^Citation45 (DACCORD)	2017	Mild to very severe COPD	Mixed	Mainly LABA/ICS or LAMA/LABA/ ICS	1,258		Mainly LAMA or LABA	Mainly LABA/LAMA/ICS	LAMA/LABA	2 years	NS
Rossi et al^Citation46 (OPTIMO)	2014	FEV1 >50% (mean 71.2%)	<2	LABA/ICS ≥1 year	914		Bronchodilator	LABA/ICS	LAMA (27%), LABA (44%), or LAMA+LABA (20%)	6 months	NS

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting β2-adrenoreceptor agonists; LAMA, long-acting muscarinic receptor antagonist; TIO, tiotropium; SAL, salmeterol; FP, fluticasone propionate; PBO, placebo; NS, not significant; IND, indacaterol; BDP, beclomethasone dipropionate; FEV₁, forced expiratory volume at the first second; OD, once daily; BID, bis in die (twice a day).

Figure 2 Simplified model for bronchodilator protection, based on ICS withdrawal studies (Table 1).

Notes: The relative size of the ellipses corresponds with the number of patients in each study. White ellipse indicates that the exacerbation rate is similar in ICS-discontinued and ICS-continued groups. Yellow ellipse indicates that the exacerbation rate is higher in the ICS-discontinued group than in the ICS-continued group. ^aICS may be beneficial in a well-defined subpopulation.
Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting β2-adrenoreceptor agonists; LAMA, long-acting muscarinic receptor antagonist.

Figure 3 De-escalation of ICS, according to WISDOM.⁵⁶

Abbreviations: ICS, inhaled corticosteroid; LAMA, long-acting muscarinic receptor antagonist; LABA, long-acting β2-adrenoreceptor agonists.

GOLDGlobal Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2017 Report)Global Initiative for Chronic Obstructive Lung Disease, Inc.2017

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