{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T03:52:45Z","timestamp":1772596365543,"version":"3.50.1"},"reference-count":5,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":1949,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>In the IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial, fluticasone furoate (FF)\/umeclidinium (UMEC)\/vilanterol (VI) significantly reduced exacerbations compared with FF\/VI or UMEC\/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To understand whether inhaled corticosteroid (ICS) withdrawal affected IMPACT results, given direct transition from prior maintenance medication to study medication at randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Exacerbations and change from baseline in trough FEV1 and St. George\u2019s Respiratory Questionnaire results were analyzed by prior ICS use. Exacerbations were also analyzed while excluding data from the first 30 days.<\/jats:p>\n                    <jats:p>Measurements and Main Results: FF\/UMEC\/VI significantly reduced the annual moderate\/severe exacerbation rate compared with UMEC\/VI in prior ICS users (29% reduction; P\u2009&amp;lt;\u20090.001), but only a numerical reduction was seen among prior ICS nonusers (12% reduction; P\u2009=\u20090.115). To minimize impact from ICS withdrawal, in an analysis excluding the first 30 days, FF\/UMEC\/VI continued to significantly reduce the annual on-treatment moderate\/severe exacerbation rate (19%; P\u2009&amp;lt;\u20090.001) compared with UMEC\/VI. The benefit of FF\/UMEC\/VI compared with UMEC\/VI was seen for severe exacerbation rates, regardless of prior ICS use (prior ICS users, 35% reduction; P\u2009&amp;lt;\u20090.001; non-ICS users, 35% reduction; P\u2009=\u20090.018), and overall when excluding the first 30 days (29%; P\u2009&amp;lt;\u20090.001). Improvements from baseline with FF\/UMEC\/VI compared with UMEC\/VI were also maintained throughout the study for both trough FEV1 and St. George\u2019s Respiratory Questionnaire, regardless of prior ICS use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data support the important treatment effects of FF\/UMEC\/VI combination therapy on exacerbation reduction, lung function, and quality of life that do not appear to be related to abrupt ICS withdrawal.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT 02164513).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201912-2478oc","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T11:49:21Z","timestamp":1593085761000},"page":"1237-1243","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":36,"title":["The Effect of Inhaled Corticosteroid Withdrawal and Baseline Inhaled Treatment on Exacerbations in the IMPACT Study. A Randomized, Double-Blind, Multicenter Clinical Trial"],"prefix":"10.1093","volume":"202","author":[{"given":"MeiLan K.","family":"Han","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard J.","family":"Criner","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark T.","family":"Dransfield","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M. G.","family":"Halpin","sequence":"additional","affiliation":[{"name":"University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Elaine","family":"Jones","sequence":"additional","affiliation":[{"name":"Development, Research and Development, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Kilbride","sequence":"additional","affiliation":[{"name":"Clinical Sciences, GlaxoSmithKline, Collegeville, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Lange","sequence":"additional","affiliation":[{"name":"Biostatistics, GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, United Kingdom"},{"name":"Department of Public Health, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Lettis","sequence":"additional","affiliation":[{"name":"Clinical Sciences, GlaxoSmithKline, Collegeville, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Lipson","sequence":"additional","affiliation":[{"name":"Medical Department, Pulmonary Section, Herlev\u2013Gentofte Hospital, Herlev, Denmark"},{"name":"Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Lomas","sequence":"additional","affiliation":[{"name":"UCL Respiratory, University College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Martin","sequence":"additional","affiliation":[{"name":"Global Medical Affairs, GlaxoSmithKline, Brentford, Middlesex, United Kingdom"},{"name":"Institute for Lung Health, University of Leicester, Leicester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Wise","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester University NHS Foundation Trust, Manchester, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando J.","family":"Martinez","sequence":"additional","affiliation":[{"name":"New York-Presbyterian Hospital\/Weill Cornell Medical Center, New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,11,1]]},"reference":[{"key":"2026030321531157500_bib1","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1056\/NEJMoa1713901","article-title":"Once-daily single-inhaler triple versus dual therapy in patients with COPD","volume":"378","author":"Lipson","year":"2018","journal-title":"N Engl J Med"},{"key":"2026030321531157500_bib2","article-title":"Assessment report: inhaled corticosteroids containing medicinal products indicated in the treatment of COPD (procedure number: EMEA\/H\/A-31\/1415)","author":"European Medicines Agency Pharmacovigilance Risk Assessment Committee","year":"2017"},{"issue":"3","key":"2026030321531157500_bib3","first-page":"CD010115","article-title":"Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease","author":"Kew","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"2026030321531157500_bib4","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1164\/rccm.201703-0449OC","article-title":"FULFIL trial: once-daily triple therapy for patients with chronic obstructive pulmonary disease","volume":"196","author":"Lipson","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030321531157500_bib5","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMe1716802","article-title":"Making sense of triple inhaled therapy for COPD","volume":"378","author":"Suissa","year":"2018","journal-title":"N Engl J Med"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/202\/9\/1237\/67176893\/ajrccm_202_9_1237.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/202\/9\/1237\/67176893\/ajrccm_202_9_1237.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T02:53:17Z","timestamp":1772592797000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/202\/9\/1237\/8495390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,1]]},"references-count":5,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,11,1]]},"published-print":{"date-parts":[[2020,11,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201912-2478oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,11]]},"published":{"date-parts":[[2020,11,1]]},"assertion":[{"value":"2019-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}