Triple Combo Therapy Reduces All-cause Mortality in COPD, Analysis Suggests

Triple therapy with fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) can reduce mortality rates among people with chronic obstructive pulmonary disease (COPD) more than VI treatment with either FF or UMEC, a new analysis of trial data suggests.

The findings were published in the American Journal of Respiratory and Critical Care Medicine, in a study titled “Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in COPD Patients.”

A Phase 3 clinical trial (NCT02164513), called Informing the Pathway of COPD Treatment (IMPACT), compared the safety and efficacy of the triple combination of FF/UMEC/VI at 100/62.5/25 micrograms for COPD treatment, to that of the dual treatment FF/VI at 100/25 micrograms, or UMEC/VI at 62.5/25 micrograms.

These three medications are all approved COPD treatments that work through different mechanisms of action.

FF is a corticosteroid that reduces inflammation. UMEC is an anticholinergic, and VI is a beta-2 agonist, and both work as bronchodilators — they relax and widen the airways in the lungs, albeit through different molecular mechanisms.

These medications have different brand names based on what combination they are used in. The triple combination is branded as Trelegy Ellipta, and is marketed by GlaxoSmithKline (GSK) and Innoviva. Of note, GSK provided funding for the IMPACT trial, as well as for the present study.

Previously reported results from IMPACT showed multiple benefits for the triple therapy compared to either dual therapy, including reduced COPD hospitalizations, fewer exacerbations, improved lung function, and higher health-related quality of life. The data also indicated potential benefits to survival after one year of treatment.

In the new study, an analysis was conducted of one-year vital data for 99.6% (all but 42 participants) of the 10,355 people enrolled in the IMPACT study.

There were 98 (2.36%) deaths in the triple therapy group, 109 (2.64%) in the FF/VI group, and 66 (3.19%) in the UMEC/VI group.

Statistical comparisons showed that the triple combination treatment resulted in a significantly lower mortality risk as compared to UMEC/VI, and it also trended toward a lower mortality risk as compared to FF/VI, but this result did not achieve statistical significance.

The researchers also conducted subgroup analyses, with a focus on whether different survival benefits were detectable among individuals who had been on different therapies prior to enrollment in IMPACT.

In total, 76.9% of participants were on a regime containing a corticosteroid (e.g. FF) prior to enrollment. Among these participants, there was a significant reduction in all-cause mortality risk if they maintained treatment with a corticosteroid than if they switched to a regime without one, such as UMEC/VI.

Additionally, 40% of participants were on a triple therapy — either FF/UMEC/VI or therapies with the same mechanisms of action — prior to enrollment. For them, staying on a triple therapy (i.e. FF/UMEC/VI) was associated with significantly reduced all-cause mortality risk, compared with FF/VI or UMEC/VI.

Overall, the results “confirmed for the first time a reduction in the risk of death using pharmacologic therapy with once-daily inhaled FF/UMEC/VI in symptomatic patients at risk for future exacerbations,” the researchers wrote.

“We believe that these data are important to healthcare providers and to patients with COPD,” they added.

The researchers noted that one limitation of their analysis is that it only assessed survival data after one year of treatment, a relatively short time frame. But, “the mortality finding in IMPACT would not be expected to be different from previous longer studies as there is no suggestion from the data, or the study population, that the benefit would wane over time,” they wrote.