Subscribe to RSS
DOI: 10.1055/s-0039-3403164
The IMPACT Trail: Single Inhaler Triple Therapy vs. dual therapies: Consistent benefit across multiple exacerbation endpoints
Publication History
Publication Date:
28 February 2020 (online)
This abstract will be presented at ERS 2019 in Madrid, Spain.
Dr. Benjamin Keller is presenting this Encore on behalf of all authors with their permissions.
Background: IMPACT is a randomized, multicenter study (52 weeks) comparing the efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) vs. FF/VI and UMEC/VI in patients ≥ 40 years of age with symptomatic COPD and a history of exacerbations (N = 10,355). For the primary endpoint, FF/UMEC/VI demonstrated a significant reduction in moderate (mod)/severe (sev) exacerbations vs. FF/VI and UMEC/VI (NEJM 2018; 378: 18).
Objectives: Evaluate the overall exacerbation benefit of FF/UMEC/VI
Methods: Sensitivity analyses were examined for the primary endpoint of annual rate mod/severe exacerbations and time-to-first mod/severe exacerbation ([Table 1]). All exacerbation endpoints analyzed (ITT population) are listed in [Table 2].
On-treatment (primary analysis) |
Poisson model on-treatment (supportive) |
On/off treatment (sensitivity) |
||||
---|---|---|---|---|---|---|
FF/UMEC/VI vs. FF/VI |
FF/UMEC/VI vs. UMEC/VI |
FF/UMEC/VI vs. FF/VI |
FF/UMEC/VI vs. UMEC/VI |
FF/UMEC/VI vs. FF/VI |
FF/UMEC/VI vs. UMEC/VI |
|
bold = p < 0.001; DC = discontinuation; TTF = time-to-first |
||||||
Annual rate mod/severe exacerbations Rate ratio (95% CI) |
0.85 (0.80, 0.90) |
0.75 (0.70, 0.81) |
0.86 (0.82, 0.90) |
0.80 (0.75, 0.84) |
0.89 (0.84, 0.94) |
0.80 (0.74, 0.86) |
On-treatment mod/severe exacerbation (primary analysis) |
On-treatment mod/severe exacerbation or premature study treatment DC (sensitivity) |
On/off treatment mod/severe exacerbation (sensitivity) |
||||
FF/UMEC/VI vs. FF/VI |
FF/UMEC/VI vs. UMEC/VI |
FF/UMEC/VI vs. FF/VI |
FF/UMEC/VI vs. UMEC/VI |
FF/UMEC/VI vs. FF/VI |
FF/UMEC/VI vs. UMEC/VI |
|
TTF Rate ratio (95% CI) |
0.85 (0.80, 0.91) |
0.84 (0.78, 0.91) |
0.81 (0.77, 0.86) |
0.82 (0.77, 0.88) |
0.87 (0.82, 0.93) |
0.86 (0.79, 0.92) |
Treatment difference (95% CI) |
||
---|---|---|
FF/UMEC/VI vs. FF/VI |
FF/UMEC/VI vs. UMEC/VI |
|
bold = p < 0.05; Abx = antibiotic; CI = confidence interval; trt = treatment; (95% Confidence Interval); *with or without antibiotics; **with or without corticosteroids; ***risk of the first and each subsequent exacerbation. The annual rate of exac was analyzed using a generalized linear model and TTF exac was analyzed using Coxʼs proportional hazards model. Both models were adjusted for the following: treatment group, gender, exac history, smoking status, baseline % predicted FEV1 and geographical region. |
||
Annual Rate Sev |
13% (− 1, 24) |
34% (22, 44) |
Time to 1st Mod/Sev |
14.8% (9.3, 19.9) |
16.0% (9.4, 22.1) |
Annual Rate Mild/Mod/Sev |
16% (11, 21) |
25% (19, 30) |
Annual Rate Mod (week 52) |
16% (10, 21) |
23% (16, 29) |
Annual Rate Corticosteroids trt* |
17% (11, 23) |
33% (27, 38) |
Annual Rate Abx trt** |
13% (7, 8) |
13% (6, 20) |
Time to Eeach Mod/Sev*** |
13.7% (8.2, 18.8) |
20.5% (14, 26.6) |
Time to Each Sev*** |
12.0% (− 1.0, 23.4) |
25.2% (12.0, 36.3) |
Time to 1st Sev |
11.2% (− 1.1, 22.1) |
25.1% (12.9, 35.6) |
Time to 1st Mild/Mod/Sev |
15.3% (10.0, 20.2) |
15.5% (9.1, 21.5) |
Time to 1st Mod |
14.9% (9.1, 20.4) |
13.5% (6.1, 20.2) |
Time to 1st Corticosteroid trt* |
16.0% (10.2, 21.5) |
21.4% (14.8, 27.5) |
Time to 1st Abx trt** |
12.3% (6.3, 18.0) |
7.6% (− 0.3, 14.9) |
Results: Results of the sensitivity analyses are consistent with the primary analysis ([Table 1]). FF/UMEC/VI vs. FF/VI and UMEC/VI showed statistically significant reduction in rate and risk of exacerbations across the majority of endpoints including steroid and antibiotic-treated events ([Table 2]).
Conclusions: FF/UMEC/VI showed significant benefit across a range of exacerbation endpoints vs. FF/VI and UMEC/VI. This underscores the robust efficacy profile of FF/UMEC/VI and supports its role in the treatment of symptomatic patients with a history of exacerbations.
Funding: GSK (Study CTT116855; NCT02164513).
#