COMPARISON BETWEEN UMEC/VI AND FF/VI BASED ON BASELINE FEV1 REVERSIBILITY: SUB-ANALYSIS FROM THE IMPACT TRIAL

SESSION TITLE: Monday Electronic Posters 5 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Analysis of treatment differences between a LAMA/LABA (UMEC/VI) vs an ICS/LABA (FF/VI) on exacerbations, lung function and health status based on patient’s baseline reversibility status, from the IMPACT (InforMing the PAthway of COPD Treatment) trial. METHODS: IMPACT was a 52 week, randomized, double-blind, parallel group, multicenter study (N=10,355) comparing efficacy and safety of once daily single inhaler triple therapy fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) 100/62.5/25μg with FF/VI 100/25μg and UMEC/VI 62.5/25μg in symptomatic patients with ≥1 COPD exacerbation in the past year despite maintenance treatment. This sub-analysis compared UMEC/VI and FF/VI based on baseline bronchodilator reversibility (defined as an increase in FEV₁ of ≥12% and ≥200ml after administration of albuterol). Pre-specified analysis was the annual rate of moderate/severe exacerbations. Post-hoc analyses included time to first (TTF) moderate/severe exacerbations, annual rate of severe exacerbations, trough FEV₁, SGRQ Total Score at week 52, and safety. The trial was not powered to analyse between-treatment differences in the outcomes by these groups. RESULTS: In the FF/VI group (n=4134), 3323 (80%) were not reversible (NR) and 810 (20%) were reversible. In the UMEC/VI group (n=2070), 1702 (82%) were NR and 366 (18%) were R. In the R group, UMEC/VI demonstrated a higher annual rate of moderate/severe exacerbations vs FF/VI (RR (rate ratio) = 1.42; 95% CI 1.19, 1.69). No treatment difference was shown in the NR group (RR=1.08; 95% CI 0.99, 1.17). TTF exacerbation was not significantly different between treatments in the R and NR groups. UMEC/VI demonstrated a statistically significant higher annual rate of severe exacerbations vs FF/VI in the R group (RR=2.11, 95% CI 1.37, 3.23,) but not in the NR group (RR=1.20, 95% CI 0.99, 1.45). At 52 weeks, UMEC/VI improved Trough FEV₁ vs FF/VI in both the R (treatment difference 70 ml; 95% CI 30, 110) and NR (treatment difference 39 ml; 95% CI 23, 55) groups. Both treatments improved the SGRQ Total Score at week 52 with no statistical difference within the R and NR groups. Adverse events were similar between groups except for incidence of pneumonia with FF/VI, 7% (both N & NR) and UMEC/VI, 4% in R and 5% in NR groups. CONCLUSIONS: In symptomatic COPD patients with exacerbations in the past year, the majority of subjects enrolled met the definition of “not reversible” which is consistent with a typical COPD population. FF/VI reduced exacerbation rates vs UMEC/VI in the reversible group, but not in the not-reversible group. UMEC/VI significantly improved lung function vs FF/VI regardless of reversibility. Adverse events were consistent with the ITT findings. CLINICAL IMPLICATIONS: Bronchodilator reversibility may help determine appropriate therapy in COPD patients. Funding: GSK (NCT02164513; study CTT116855) DISCLOSURES: Employee relationship with Glaxosmithkline Please note: >$100000 Added 03/14/2019 by Isabelle BOUCOT, source=Web Response, value=Salary Employee relationship with GlaxoSmithKline Please note: >$100000 Added 03/14/2019 by Isabelle BOUCOT, source=Web Response, value=Shares Removed 03/14/2019 by Isabelle BOUCOT, source=Web Response Employee relationship with Glaxosmithkline Please note: >$100000 Added 03/14/2019 by Isabelle BOUCOT, source=Web Response, value=Shares Employee relationship with GSK Please note: $1-$1000 Added 03/12/2019 by Erin Drew, source=Web Response, value=Salary Stock/share holder relationship with GSK Please note: $1-$1000 Added 03/12/2019 by Erin Drew, source=Web Response, value=Stocks/shares No relevant relationships by Gregory Feldman, source=Web Response Consultant relationship with GSK Please note: $20001 - $100000 Added 03/13/2019 by MeiLan Han, source=Web Response, value=Consulting fee Consultant relationship with BI Please note: $20001 - 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