New research published in the New England Journal of Medicine has shown triple therapy better reduces moderate/severe exacerbations compared with dual therapy
Results from the IMPACT study, one of the largest ever studies conducted in patients with moderate to severe chronic obstructive pulmonary disease (COPD), has found use of Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol) achieved superiority to two different classes of dual combination therapy.
The IMPACT trial was a phase 3, randomised, double-blind, parallel-group, multicentre trial involving 10,355 patients with COPD across 37 countries.
Once-daily use of Trelegy Ellipta was compared with Anoro Ellipta (a LAMA/LABA) and Breo Ellipta (an ICS/LABA) over 52 weeks, with the primary outcome being the annual rate of moderate/severe COPD exacerbations during treatment (p<0.001).
The study showed a 25% reduction in moderate/severe exacerbations for Trelegy compared with Anoro (0.91 vs 1.21 per year, p<0.001), and a 15% reduction for Trelegy compared with Breo (0.91 vs 1.07 per year, p<0.001).
Once-daily single-inhaler triple therapy with fluticasone furoate, umeclidinium and vilanterol resulted in a significantly lower rate of moderate or severe COPD exacerbations, better lung function and health-related quality of life than dual therapy, the authors concluded.
These benefits were observed regardless of the patients’ blood eosinophil levels at randomisation.
The adverse-event profile of triple therapy was similar to that of dual-therapy comparators, and there were no new safety findings associated with use of an inhaled glucocorticoid, a LAMA, or a LABA in combination.
According to Professor Phil Bardin from Monash Medical Centre, the IMPACT findings are important because they point to the prospect of reduced exacerbations in the future for patients being treated for COPD.
“Triple therapy is an emerging option for COPD and we’re always looking at new ways to reduce exacerbations for our patients,” said Professor Bardin, who was an IMPACT study trial lead.
“New options with good evidence behind them are always going to be of interest for the future.”
However in an accompanying editorial, NEJM‘s Editor-in-Chief Dr Jeffrey Drazen and corresponding author Dr Samy Suissa say that while the IMPACT trial has several strengths, there are also some weaknesses to take into account.
They say the results of the trial are “challenging to interpret” because nearly 40% of patients enrolled were receiving treatment with triple therapy, more than 70% were receiving an inhaled glucocorticoid, and patients with a history of asthma were included in the study.
The authors add that for the patients assigned to the LAMA-LABA group in the study, inhaled glucocorticoids were “abruptly withdrawn” at time of randomisation, which could lead to COPD exacerbations.
“This design peculiarity, compounded by the probably inclusion of some patients who could have met a standard case definition of asthma, could explain the rapid surge in exacerbations observed in the first month after randomisation in the LAMA-LABA group; during the subsequent 11 months of follow-up, the incidence of exacerbation with LAMA-LABA was practically identical to that with triple therapy.”
Dr Drazen and Dr Suissa conclude that “as such, we think that the IMPACT trial falls short of providing the awaited robust evidence to better understand the potential for stepping up to single-inhaler triple therapy in clinical practice.
“Until further evidence is available, we think that clinicans should rely of the updated GOLD 2017 guidelines recommending that escalation to triple therapy occur only after maximised bronchodilator treatment with LAMA-LABA regimens and be limited to patients with more symtomatic GOLD group D COPD with frequent exacerbations.”
In Australia, exacerbations of COPD account for around 355,328 hospital bed days and 15% of all potentially preventable hospitalisations each year.
Declarations: The trial was designed by academic partners and the sponsor GSK, which also paid for editorial support for the NEJM article. The lead author is an employee of GSK, which is a sponsor for Trelegy Ellipta.
Note: This article was edited to add further detail on the accompanying editorial in the NEJM.
See the original article in The New England Journal of Medicine here.