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The Effect of ICS Withdrawal and Baseline Inhaled Treatment on Exacerbations in the IMPACT Study: A Randomized, Double-blind Multicenter Trial

Han, MK; Criner, GJ; Dransfield, MT; Halpin, DMG; Jones, CE; Kilbride, S; Lange, P; ... Martinez, FJ; + view all (2020) The Effect of ICS Withdrawal and Baseline Inhaled Treatment on Exacerbations in the IMPACT Study: A Randomized, Double-blind Multicenter Trial. American Journal of Respiratory and Critical Care Medicine 10.1164/rccm.201912-2478OC. (In press). Green open access

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Abstract

RATIONALE: In the IMPACT trial fluticasone furoate/umeclidinium/ vilanterol (FF/UMEC/VI) significantly reduced exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations. OBJECTIVES: Understand whether inhaled corticosteroid (ICS) withdrawal affected IMPACT results given direct transition from prior maintenance medication to study medication at randomization. METHODS: Exacerbations and change from baseline in trough forced expiratory volume in 1 second (FEV1) and St George's Respiratory Questionnaire (SGRQ) were analyzed by prior ICS use. Exacerbations were also analyzed excluding data from the first 30 days. MEASUREMENTS AND MAIN RESULTS: FF/UMEC/VI significantly reduced annual moderate/severe exacerbation rate versus UMEC/VI in prior ICS users (29% reduction; p<0.001), but only a numerical reduction was seen among prior ICS non-users (12% reduction; p=0.115). To minimize impact from ICS withdrawal, in an analysis excluding the first 30 days, FF/UMEC/VI continued to significantly reduce annual on-treatment moderate/severe exacerbation rate (19%; p<0.001) versus UMEC/VI. Benefit of FF/UMEC/VI versus UMEC/VI was seen for severe exacerbation rates, regardless of prior ICS use (prior ICS users: 35% reduction, p<0.001; non-ICS users: 35% reduction, p=0.018) and overall when excluding the first 30 days (29%, p<0.001). Improvements from baseline with FF/UMEC/VI versus UMEC/VI were also maintained throughout the study for both trough FEV1 and SGRQ regardless of prior ICS use. CONCLUSIONS: These data support important treatment effects from 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. FUNDING: GSK (CTT116855/NCT02164513). Clinical trial registration available at www.clinicaltrials.gov, ID: NCT02164513. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Type: Article
Title: The Effect of ICS Withdrawal and Baseline Inhaled Treatment on Exacerbations in the IMPACT Study: A Randomized, Double-blind Multicenter Trial
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1164/rccm.201912-2478OC
Publisher version: https://doi.org/10.1164/rccm.201912-2478OC
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: COPD, Step down, Triple therapy
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > VP: Health
URI: https://discovery.ucl.ac.uk/id/eprint/10105567
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