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

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.