Q: What are the benefits and risks of inhaled corticosteroids for COPD? A: Inhaled corticosteroids (ICS), either alone or with a long-acting [beta] agonist (LABA), reduce the frequency of exacerbations of chronic obstructive pulmonary disease (COPD) and statistically, but not clinically, improve quality of life (QOL) (strength of recommendation [SOR]: B, meta-analyses of heterogeneous studies). However, ICS have no mortality benefit and don't consistently improve forced expiratory volume in 1 second (FEV1) (SOR: B, meta-analyses of secondary outcomes). They increase the risk of pneumonia, oropharyngeal candidiasis, and bruising (SOR: B, meta-analyses of secondary outcomes). Withdrawal of ICS doesn't significantly increase the risk of COPD exacerbation (SOR: B, a meta-analysis)

Hamilton, Tanya

Miller, John B.

St. Anna, Leilani

Vincent, E. Chris

English

University of Missouri: MOspace

Evidence-based answers from the Family Physicians Inquiries Network276 ThE JourNal oF FamIly PracTIcE  |   may 2014  |   Vol 63, No 5clinical inquiriesEvidEncE-basEd answErATanya Hamilton, MD Montana Family Medicine Residency—Riverstone Health, Billings, Mont John B. Miller, MD Family Medicine Residency of Western Montana, Partnership Health Center, Missoula E. Chris Vincent, MD Department of Family Medicine, University  of Washington, SeattleLeilani St. Anna, MLIS, AHIPUniversity of Washington Health Sciences Library, Seattle ASSISTAnT EDITORRichard Guthmann, MD, MPHAdvocate Illinois Masonic Family Medicine Residency, University of Illinois at Chicago	 What	are	the	benefits	and	risks	of	inhaled	corticosteroids	for	COPD?		 Inhaled corticosteroids (ICS),		 either	 alone	 or	 with	 a	 long-acting		 agonist	 (LABA),	 reduce	 the	 frequency	of	 exacerbations	 of	 chronic	 obstructive	pulmonary	 disease	 (COPD)	 and	 statisti-cally,	but	not	clinically,	improve	quality	of	life	 (QOL)	 (strength	 of	 recommendation	[SOR]:	B,	meta-analyses	of	heterogeneous	studies).	However,	 ICS	 have	 no	 mortality	 ben-efit	and	don’t	consistently	improve	forced	expiratory	 volume	 in	 1	 second	 (FEV1)	(SOR:	B,	meta-analyses	of	secondary	out-comes).	 They	 increase	 the	 risk	 of	 pneu-monia,	 oropharyngeal	 candidiasis,	 and	bruising	 (SOR: B,	 meta-analyses	 of	 sec-ondary	outcomes).	Withdrawal	of	ICS	doesn’t	significant-ly	increase	the	risk	of	COPD	exacerbation	(SOR:	B,	a	meta-analysis).Evidence summaryA	 Cochrane	 meta-analysis	 designed	 to	 de-termine	 the	 efficacy	 of	 ICS	 in	 patients	 with	stable	 COPD	 found	 55	 randomized,	 con-trolled	 trials	 (RCTs)	 with	 a	 total	 of	 16,154	participants	that	compared	ICS	with	placebo	for	2	weeks	to	3	years	duration.1	COPD	varied	from	moderate	to	severe	in	most	studies.	In	 pooled	 data,	 ICS	 for	 2	 or	 more	 years	didn’t	 consistently	 improve	 lung	 function,	the	 primary	 outcome	 (TABLE).	 However,	 the	largest	 RCT	 (N=2617)	 of	 3	 years	 duration	showed	 a	 small	 decrease	 in	 decline	 of	 FEV1	(55	 mL	 compared	 with	 42	 mL,	 P	 value	 not	provided).	 Regarding	 the	 secondary	 out-comes	of	mortality	and	exacerbations,	ICS	for	a	 year	 or	 longer	 didn’t	 reduce	 mortality	 but	decreased	exacerbations	by	19%.	Clinically	 significant	 adverse	 effects	 of	ICS	 use	 included	 pneumonia,	 oropharyn-geal	candidiasis,	and	bruising;	for	ICS	treat-ment	 longer	 than	 one	 year,	 the	 numbers	needed	to	harm	(NNH)	compared	with	pla-cebo	were	30,	27,	and	32,	respectively.	Bone	fractures	weren’t	more	common	among	ICS	users.	Investigators	 observed	 a	 statistical,	 but	not	 clinical,	 QOL	 benefit	 as	 measured	 by	the	 St.	 George’s	 Respiratory	 Questionnaire	(SGRQ)	in	5	RCTs	with	a	total	of	2507	patients	(mean	difference,	‒1.22	units/year;	95%	con-fidence	interval,	‒1.83	to	‒.60).	The	minimum	clinically	important	difference	on	the	76-item	questionnaire	was	4	units.2Adding ICS to LABA increases risk of pneumonia and candidiasisA	Cochrane	meta-analysis	of	14	double-blind	RCTs	comprising	a	total	of	11,794	participants	with	severe	COPD	compared	LABA	plus	ICS	with	 LABA	 alone	 over	 8	 weeks	 to	 3	 years.3	Primary	outcomes	were	exacerbations,	mor-tality,	hospitalizations,	and	pneumonia.	Sec-ondary	 outcomes	 included	 oropharyngeal	candidiasis	and	health-related	QOL.	The	 LABA-plus-ICS	 group	 had	 lower	rates	of	exacerbations	than	the	LABA	group,	but	 the	 data	 were	 of	 low	 quality	 because	 of	significant	heterogeneity	among	studies	and	high	 rates	 of	 attrition.	 No	 significant	 differ-ence	 in	 mortality	 or	 hospitalizations	 was	found	between	the	groups.	The	risk	of	pneu-277JFPoNlINE.com Vol 63, No 5  |  may 2014  |  ThE JourNal oF FamIly PracTIcEmonia	in	the	LABA-plus-ICS	group	was	high-er	than	in	the	LABA-alone	group,	with	a	NNH	of	48.	Candidiasis	 occurred	 more	 often	 in	 pa-tients	 on	 combination	 fluticasone	 and	 sal-meterol	 than	 salmeterol	 alone,	 with	 a	 NNH	of	22.	QOL	scores	(measured	by	the	SGRQ)	in	patients	on	combination	therapy	were	statisti-cally	better,	but	clinically	insignificant.Discontinuing ICS  doesn’t increase exacerbationsA	 meta-analysis	 of	 3	 RCTs	 that	 enrolled	 a	total	 of	 877	 patients	 with	 COPD	 compared	TABLEWhat	RCTs	reveal	about	benefits	and	harms	of	inhaled	corticosteroids		in	patients	with	chronic,	stable	COPD1,3comparison medicationsoutcome  studiedNumber  of studiesNumber of participantsTreatment duration measurement  Value 95% cIresult favorsPlacebo vs IcS (BuD, BDP, FP, mF, or Taa at various doses)lung function 5 2333 2-3 yr Difference in decline of FEV1 5.8 ml/yr NS Neitherlung function 5 4823 2-3 yr Difference in mean change in FEV1 6.9 ml/yr 1.8-12 IcSmortality 9 8390 1-3 yr or 1 NS NeitherExacerbations per patient per yr5 2253 1-3 yr Difference in mean number of exacerbations-.26 -.3 to -.8 IcSPneumonia 7 6235 1-3 yr or 1.6 1.3-1.9 Placebocandidiasis 6 5586 1-3 yr or 2.6 2-3.5 Placebo Bruising 5 5073 1-3 yr or 1.6 1.3-2 Placebo Fractures 4 5226 1-3 yr or 1 NS NeitherIcS+laBa (FPS) vs laBa (Sal)lung function 5 2390 8-52 wk change from baseline in predose FEV1 70 ml 5-100 IcS+ laBaIcS+laBa (BDF) vs laBa (For)lung function 2 1203 8-52 wk change from baseline in predose FEV1 50 ml 0-90 IcS+ laBaIcS+laBa (FPS or BDF) vs laBa (Sal or For)mortality 10 10,681 median 1 yr (range 24-156 wk)rate ratio .9 NS Neitherhospitalizations 3 4879 1-3 yr rate ratio .8 NS NeitherExacerbations per patient per year9 9921 median 1 yr (range 24-156 wk)rate ratio .8 .7-.8 IcS+ laBaPneumonia 12 11,076 median 1 yr (range 8-156 wk)or 1.6 1.2-2 laBa aloneIcS+laBa (FPS) vs laBa (Sal)candidiasis 6 3118 median 1 yr (range 8-156 wk)or 3.8 2.3-6 laBa aloneBDF, budesonide and formoterol; BDP, beclomethasone dipropionate; BuD, budesonide; cI, confidence interval; coPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; For, formoterol; FP, fluticasone propionate; FPS, fluticasone propionate and salmeterol; IcS, inhaled corticosteroids; laBa, long-acting  agonist; mF, mometasone furoate; NS, not significant; or, odds ratio; rcT, randomized controlled trial; Sal, salmeterol; Taa, triamcinolone acetonide. coNTINuED oN PagE 280ThE JourNal oF FamIly PracTIcE  |   may 2014  |   Vol 63, No 5clinical inquiriesreferencesthe	number	of	exacerbations	in	patients	who	continued	fluticasone	500	mcg	 inhaled	 twice	daily	and	patients	who	were	withdrawn	from	the	medication.	All	patients	had	been	treated	with	ICS	for	at	 least	3	months,	and	had	been	on	 fluticasone	 for	 at	 least	 2	 weeks.	 Subjects	had	 a	 baseline	 FEV1	 between	 25%	 and	 80%	predicted. No	significant	increase	in	exacerba-tions	occurred	after	discontinuing	ICS.4Recommendations The	American	College	of	Physicians,	Ameri-can	 College	 of	 Chest	 Physicians,	 American	Thoracic	Society,	and	European	Respiratory	Society,	 in	 a	 joint	 guideline,	 recommend	against	 using	 ICS	 as	 monotherapy	 for	 pa-tients	 with	 stable	 COPD.	 They	 acknowledge	that	 these	 drugs	 are	 superior	 to	 placebo	 in	reducing	 exacerbations,	 but	 note	 that	 con-cerns	about	their	side-effect	profile	(thrush,	potential	for	bone	loss,	and	moderate	to	se-vere	 easy	 bruisability)	 make	 them	 less	 de-sirable	 than	 LABAs	 or	 long-acting	 inhaled	anticholinergics.5	The	 Global	 Initiative	 for	 Chronic	 Ob-structive	 Lung	 Disease	 likewise	 discourages	long-term	 use	 of	 ICS	 because	 of	 the	 risk	 of	pneumonia	and	fractures.6	Both	groups	note	that	 patients	 with	 severe	 COPD	 may	 benefit	from	a	combination	of	ICS	and	a	long-acting	medication	(usually	a	LABA).																										JFP	 1.			Yang	IA,	Clarke	MS,	Sim	EH,	et	al.	Inhaled	corticosteroids	for	stable	chronic	obstructive	pulmonary	disease.	Cochrane Da-tabase Syst Rev.	2012;(7):CD002991.		 2.			Jones	 PW.	 St.	 George’s	 Respiratory	 Questionnaire:	 MCID.	COPD.	2005;2:75-79.		 3.			Nannini	 LJ,	 Lasserson	 TJ,	 Poole	 P.	 Combined	 corticosteroid	and	 long-acting	 beta(2)-agonist	 in	 one	 inhaler	 versus	 long-acting	 beta(2)-agonists	 for	 chronic	 obstructive	 pulmonary	disease.	Cochrane Database Syst Rev. 2012;9:CD006829.		 4.			Nadeem	NJ,	Taylor	SJ,	Eldridge	SM.	Withdrawal	of	inhaled	cor-ticosteroids	in	individuals	with	COPD—a	systemic	review	and	comment	on	trial	methodology.	Respir Res.	2011;12:107.		 5.			Qaseem	A,	Wilt	TJ,	Weinberger	SE,	et	al;	American	College	of	Physicians;	 American	 Thoracic	 Society;	 European	 Respira-tory	 Society.	 Diagnosis	 and	 management	 of	 stable	 chronic	obstructive	 pulmonary	 disease:	 a	 clinical	 practice	 guideline	update	 from	 the	 American	 College	 of	 Physicians,	 American	College	of	Chest	Physicians,	American	Thoracic	Society,	and	European	 Respiratory	 Society.	 Ann Intern Med.	 2011;155:179-191.		 6.			Global	Initiative	for	Chronic	Obstructive	Lung	Disease	Web	site.	Global	 strategy	 for	 the	 diagnosis,	 management	 and	 prevention	of	COPD.	2014.	Available	at:	www.goldcopd.org/uploads/users/files/GOLD_Report2014_Feb07.pdf.	Accessed	April	4,	2013.	coNTINuED From PagE 277This supplement is sponsored by Primary Care Education Consortium and Primary Care Metabolic Group. It is supported by educational grants from Allergan, Inc. and funding from AstraZeneca; Duchesnay USA; Horizon Pharma, Inc.; and Novo Nordisk, Inc.Topics covered in this comprehensive update include:•   Antiplatelet Therapy in Women With Acute Coronary Syndrome•   Coronary Heart Disease in Women•  Obesity in Women•  Type 2 Diabetes Mellitus in Women•   Rheumatoid Arthritis: Early Treatment With Corticosteroids and Nonsteroidal Anti-inflammatory Drugs•   The Pharmacologic Management of Nausea and Vomiting of Pregnancy•   The Pharmacologic Management of Idiopathic Overactive Bladder in Primary Care•  Chronic Migraine in WomenWith an Introduction by Stephen A. Brunton, MD, FAAFPA SPECIAl SuPPlEMENT ON WOMEN’S HEAlTHAVAILABLE NOW IN PRINT AND ONLINEAVAIlABlE NOW AT jfPONlINE.COMFREE 1.0 CME CREditFREE 1.0 CME CREdit

What are the benefits and risks of inhaled corticosteroids for COPD?

https://mospace.umsystem.edu/xmlui/bitstream/10355/43044/1/InhaledCorticosteroids.pdf

What are the benefits and risks of inhaled corticosteroids for COPD?

Abstract

Similar works

Full text

Available Versions

University of Missouri: MOspace