Pneumologie 2020; 74(S 01): 46
DOI: 10.1055/s-0039-3403164
Posterbegehung (PO08) – Sektion Klinische Pneumologie
Klinische Studien bei COPD und Asthma
Georg Thieme Verlag KG Stuttgart · New York

The IMPACT Trail: Single Inhaler Triple Therapy vs. dual therapies: Consistent benefit across multiple exacerbation endpoints

M Han
1   University of Michigan, Pulmonary & Critical Care, Ann Arbor, MI, USA
,
G Criner
2   Lewis Katz School of Medicine at Temple University, Philadelphia, Pa, USA
,
M Dransfield
3   Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, Al, USA
,
D Halpin
4   Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK
,
C Jones
5   GlaxoSmithKline, Research Triangle Park, Nc, USA
,
S Kilbride
6   GlaxoSmithKline, Stockley Park, UK
,
P Lange
7   Department of Public Health, University of Copenhagen, Copenhagen, Denmark
,
D Lomas
8   Ucl Respiratory, University College London, London, UK
,
FJ Martinez
9   Weill Cornell Medicine, New York, Ny, USA
,
H Quasny
5   GlaxoSmithKline, Research Triangle Park, Nc, USA
,
D Singh
10   Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK
,
R Wise
11   Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
,
D Lipson
12   GlaxoSmithKline, Collegeville, Perelman School of Medicine, University of Pennsylvania, Pa, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
28 February 2020 (online)

Also available at
 

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].

Table 1 Sensitivity analyses.

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)

Table 2 On-treatment COPD exacerbation endpoints (ITT).

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).