The effect of inhaled corticosteroid withdrawal and baseline inhaled treatment on exacerbations in the IMPACT study a randomized, double-blind, multicenter clinical trial

Mei Lan K. Han, Gerard J. Criner, Mark T. Dransfield, David M.G. Halpin, C. Elaine Jones, Sally Kilbride, Peter Lange, Sally Lettis, David A. Lipson, David A. Lomas, Neil Martin, Robert A. Wise, Dave Singh, Fernando J. Martinez

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1237-1243
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume202
Issue number9
DOIs
StatePublished - Nov 1 2020

Keywords

  • Chronic obstructive pulmonary disease
  • Step down
  • Triple therapy

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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