TY - JOUR
T1 - The effect of inhaled corticosteroid withdrawal and baseline inhaled treatment on exacerbations in the IMPACT study a randomized, double-blind, multicenter clinical trial
AU - Han, Mei Lan K.
AU - Criner, Gerard J.
AU - Dransfield, Mark T.
AU - Halpin, David M.G.
AU - Elaine Jones, C.
AU - Kilbride, Sally
AU - Lange, Peter
AU - Lettis, Sally
AU - Lipson, David A.
AU - Lomas, David A.
AU - Martin, Neil
AU - Wise, Robert A.
AU - Singh, Dave
AU - Martinez, Fernando J.
N1 - Funding Information:
Supported by GlaxoSmithKline, which funded the study (study number CTT116855; NCT 02164513) and editorial support. The funders of the study had a role in the study design, data analysis, data interpretation, and writing of the report.
Funding Information:
Acknowledgment: The authors thank Holly Quasny of GlaxoSmithKline for her contributions to data analysis and interpretation. Editorial support (in the form of assembling figures, collating author comments, and grammatical editing) was provided by Chrystelle Rasamison, Ph.D., at Fishawack Indicia, Ltd., United Kingdom. Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC).
Publisher Copyright:
Copyright © 2020 by the American Thoracic Society
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Rationale: 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. Objectives: To 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 FEV1 and St. George’s Respiratory Questionnaire results were analyzed by prior ICS use. Exacerbations were also analyzed while excluding data from the first 30 days. 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, 0.001), but only a numerical reduction was seen among prior ICS nonusers (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 the annual on-treatment moderate/severe exacerbation rate (19%; P, 0.001) 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, 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 compared with UMEC/VI were also maintained throughout the study for both trough FEV1 and St. George’s Respiratory Questionnaire, regardless of prior ICS use. Conclusions: 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.
AB - Rationale: 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. Objectives: To 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 FEV1 and St. George’s Respiratory Questionnaire results were analyzed by prior ICS use. Exacerbations were also analyzed while excluding data from the first 30 days. 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, 0.001), but only a numerical reduction was seen among prior ICS nonusers (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 the annual on-treatment moderate/severe exacerbation rate (19%; P, 0.001) 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, 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 compared with UMEC/VI were also maintained throughout the study for both trough FEV1 and St. George’s Respiratory Questionnaire, regardless of prior ICS use. Conclusions: 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.
KW - Chronic obstructive pulmonary disease
KW - Step down
KW - Triple therapy
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U2 - 10.1164/rccm.201912-2478OC
DO - 10.1164/rccm.201912-2478OC
M3 - Article
C2 - 32584168
AN - SCOPUS:85094983795
SN - 1073-449X
VL - 202
SP - 1237
EP - 1243
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 9
ER -