23 April 2018

Triple therapy for COPD: one-puff wonder?

Chronic Disease Clinical Respiratory

Patients with severe COPD and frequent exacerbations are the likely winners, following study findings supporting the value of triple inhaler therapy including a glucocorticoid in this group.

The year long, international, randomised trial, known as the IMPACT trial, involving more than 10,000 COPD patients, investigated whether the daily dose of the triple inhaled therapy (a glucocorticoid, a LAMA and a LABA) made a difference to the rate of moderate and severe exacerbations compared with using either an inhaled glucocorticoid/LABA combination or a LABA/LAMA combination.

Overall, the triple therapy (fluticasone furoate, umeclidinium and vilanterol) resulted in fewer exacerbations than both the LABA/LAMA (0.91 per year versus 1.21 per year) and the glucocorticoid/LABA therapy (0.91 vs 1.07), according to the study findings published in The New England Journal of Medicine. 

In addition, the triple therapy resulted in fewer hospitalisations due to COPD than the LAMA/LABA group.

The study was funded by GlaxoSmithKline and the all the inhalers used by participants were the company’s Ellipta devices. In brand-name speak, the researchers were comparing the new Trelegy inhaler with the Anoro and Breo therapies. Trelegy was recommended for PBS Authority listing by the PBAC last December.

Current guidelines already recommend triple therapy for patients who still get moderate to severe exacerbations of their COPD despite optimal treatment with either one of the currently available dual combination therapies. However, until this new triple inhaler became available this meant patients needed to be taking multiple inhalers several times a day. 

What’s more, there hasn’t been much evidence to date to support this step-up to triple therapy over the dual therapy. 

“Controversy exists regarding the use of inhaled glucocorticoids in COPD and the relative benefits of triple therapy as compared with dual therapy (inhaled-glucocorticoid-LABA or LAMA-LABA) in patients with a history of exacerbations,” the study authors said.

Consequently, the finding of a 25% reduction in exacerbations with the triple therapy compared with LAMA/LABA combination, and even a 15% reduction compared with the glucocorticoid/LABA combination is seen as significant.

But an accompanying editorial suggests a “peculiarity” in the IMPACT study design limits its value in terms of providing the much-awaited robust evidence for the triple therapy over and above the dual therapy. 

The editorial authors point out that many patients enrolled in the study were actually taking triple therapy, including an inhaled glucocorticoid, at baseline. Also, patients with asthma were not excluded from the trial. Many patients randomised to the LAMA/LABA actually had their inhaled glucocorticoid abruptly stopped, they said.

“This 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,” they said.

As a result, the benefit of the triple therapy might have been exaggerated, they suggest.

And while the triple therapy will have obvious advantages in terms of simplicity of treatment of COPD, the editorial authors warn that it should still be reserved only for those patients with severe disease and recurrent symptomatic exacerbations, which, in fairness, the study authors recommend as well.


DOI: 10.1056/NEJMoa1713901

DOI: 10.1056/NEJMe1716802