Single Inhaler Triple Therapy (FF/UMEC/VI) Versus FF/VI and UMEC/VI in Patients with COPD: Subgroup Analysis of the China Cohort in the IMPACT Trial

Abstract Background In the Phase III InforMing the PAthway of COPD Treatment (IMPACT) trial, fluticasone furoate [FF]/umeclidinium [UMEC]/vilanterol [VI] single-inhaler triple therapy resulted in lower rates of moderate/severe exacerbations than dual therapy with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations. Here we present the result in the subpopulation of patients enrolled in China. Methods The IMPACT trial was a 52-week, randomized, double-blind, parallel-group, multicenter trial. Patients (≥40 years of age) with COPD and ≥1 moderate/severe exacerbations in the prior year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg administered via the Ellipta inhaler. Endpoints, assessed in the overall intent-to-treat (ITT) population and in patients from China, included annual rates of exacerbations, time-to-first on-treatment moderate/severe exacerbation, and change from baseline in trough forced expiratory volume in 1 second (FEV1) at Week 52. Results Of the 10,355 patients randomized, 535 (5.2%) were from China. In the China cohort, the rate of on-treatment moderate/severe exacerbations was 0.81 per year with FF/UMEC/VI versus 0.96 with FF/VI (rate ratio [RR]: 0.84; 95% confidence interval [CI]: 0.64, 1.11; p=0.227) and 0.80 with UMEC/VI (RR: 1.02; 95% CI: 0.72, 1.44; p=0.929). Hazard ratio for time-to-first moderate/severe exacerbation was 0.84 (95% CI: 0.63, 1.11; p=0.218) for FF/UMEC/VI versus FF/VI, and 0.89 (95% CI: 0.62, 1.27; p=0.516) for FF/UMEC/VI versus UMEC/VI. Improvements in mean change from baseline in trough FEV1 were observed for FF/UMEC/VI versus FF/VI (treatment difference 137 mL; 95% CI: 86, 188; p<0.001) and FF/UMEC/VI versus UMEC/VI (treatment difference 63 mL; 95% CI: 0, 125; p=0.0.050) in China. Health status was also improved with FF/UMEC/VI versus both dual therapies. Broadly, these results were in the same direction as those seen in the overall ITT population. No new safety signals were identified. Conclusions In the China cohort of the IMPACT trial, single-inhaler triple therapy with FF/UMEC/VI versus dual therapy with FF/VI or UMEC/VI reduced the rate and risk of exacerbations, and improved lung function and quality of life similar to the overall ITT population. Trial registration: NCT02164513 (GSK study number CTT116855).