A once-daily inhaler combination of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI; Trelegy Ellipta) reduced all-cause mortality in patients with chronic obstructive pulmonary disease (COPD)
by 42%, according to recent study findings.
The findings came from an expanded analysis of data from the 37-country phase 3 InforMing the PAthway of COPD Treatment (IMPACT) trial.
David Lipson, MD, and a team of investigators randomized more than 10,000 IMPACT participants who had COPD and were at-risk for severe exacerbations into 1 of 3 groups: once-daily inhalations of FF/UMEC/VI, FF/VI, or UMEC/VI combinations. Patients included had symptomatic COPD with a forced expiratory volume in 1 second (FEV1
) <50% of predicted and a history of >
1 moderate or severe exacerbation or FEV1
of 50% to <80% of predicted >
2 moderate or 1 severe exacerbation in the previous year.
Lipson, the senior director of clinical sciences at GlaxoSmithKline, designed the study to consist of a two-week period where participants remained on their own medication, a 52-week treatment period, and a one-week safety follow-up.
Overall, 10,355 participants were randomized into the team’s intent to treat population and got study medication. A majority of the patients (66%) were male and the mean age was 65.3 years old.
If a patient entered the study on a triple therapy or an inhaled corticosteroid (ICS)-containing regimen, they had lower lung function, a greater history of hospitalization over the previous 12 months, and were less likely to be a smoker compared to those who entered on a dual or monotherapy.
There were 50 (1.2%) on-treatment deaths in the FF/UMEC/VI arm (n=4151), 49 (1.19%) in the FF/VI arm (n = 4 134), and 39 (1.88%) in the UMEC/VI arm (n = 2070).
The hazard ratio for on-treatment all-cause mortality for the comparison of FF/UMEC/VI with UMEC/VI was .58 (95% CI; .38 -.88; P
= .011), and .61 (95% CI; .4 -.93; P
= .022) for the comparison of FF/VI with UMEC/VI.
When Lipson and the team analyzed the primary cause of death, there were lower rates of cardiovascular and respiratory deaths, as well as death associated with the patient’s underlying COPD when on a randomized ICS-containing arm compared to UMEC/VI.
Additional data collection provided vital status at week 52 for almost all of the population (99.6%). There were 27 additional off-treatment deaths identified in the post hoc collection (9 on FF/UMEC/VI, 12 on FF/VI, and 6 on UMEC/VI). There were 98 (2.36%) deaths on FF/UMEC/VI, 109 (2.64%) on FF/VI, and 66 (3.19%) on UMEC/VI.
Time to all-cause mortality showed a HR of .72 for those treated with FF/UMEC/VI compared to UMEC/VI (95% CI, .53-.99; P
= .042). The HR for FF/VI compared to UMEC/VI was .82 (95% CI, .6-1.11; P
The mortality finding was primarily driven by the steroid component and its effects on reducing exacerbations, Lipson said in a statement
“These new repeat analyses demonstrate the robustness of the original finding,” he said. “We have concluded that we can improve survival in symptomatic patients with COPD at-risk of exacerbation.”
The study, “Reduction in All-Cause Mortality With Fluticasone Furoate/Umeclidinium/Vilanterol in COPD Patients
,” was published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine