Single-inhaler triple therapy for COPD confers greater benefits than dual therapies

The use of single-inhaler triple therapy yields meaningful improvements across a range of chronic obstructive pulmonary disease (COPD) endpoints over time compared with dual therapies, according to data from the IMPACT* trial presented at the 2019 European Respiratory Society (ERS) International Congress.

“Together with the reduction in rate and risk of exacerbation previously reported, these results underscore the consistent efficacy profile of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and supports its role in the treatment of symptomatic patients with a history of exacerbations,” the investigators said. [N Engl J Med 2018; 378:1671-1680]

The 52-week phase III IMPACT study included 10,355 patients who were randomized to receive either once-daily single-inhaler triple therapy with FF 100 µg/UMEC 62.5 µg/VI 25 µg (n=4,151) or dual therapy with either FF 100 µg/VI 25 µg (n=4,134) or UMEC 62.5 µg/VI 25 µg (n=2,070). All patients were ≥40 years with symptomatic COPD Assessment Test (CAT) score ≥10.

Prespecified endpoints were trough forced expiratory volume in 1 s (FEV₁) at weeks 4, 16, 28, 40 and 52; and St. George's Respiratory Questionnaire (SGRQ), Transition Dyspnea Index (TDI), and COPD Assessment Test (CAT) at weeks 4, 28 and 52.

Compared with the dual therapies, FF/UMEC/VI conferred greater benefits for through FEV1 at week 4 and these improvements were maintained at every subsequent follow-up through weeks 52 (p-all<0.001). [ERS 2019, abstract PA2482]

Likewise, the triple therapy produced greater improvements in SGRQ total score at all time points. The gains were greater at week 28 than at week 4 and were sustained until week 52.

Triple therapy further showed superiority over dual therapies in terms of the CAT score at all time points, except against UMEC/VI at week 28.

In terms of TDI focal score improvements, triple therapy outdid FF/VI at all time points as well as UMEC/VI but only at week 4.

“The Global Initiative for Chronic obstructive Lung Disease (GOLD) management strategy recommends triple therapy with an inhaled corticosteroid (ICS), a long-acting muscarinic antagonist and a long-acting β2 agonist (LABA) for patients with COPD who experience clinically significant symptoms despite treatment with an ICS/LABA or LAMA/LABA and who are at increased risk of exacerbations,” the investigators noted.

“In the IMPACT trial once-daily single-inhaler triple therapy with FF/UMEC/VI significantly reduced moderate/severe exacerbations and improved lung function and health-related quality of life compared with dual therapy with FF/VI or UMEC/VI in patients with symptomatic COPD and a history of exacerbations,” they added.

The investigators stressed the importance of establishing in the current analysis how early the between-treatment differences can be observed and how consistent they are over time.

*InforMing the PAthway of COPD Treatment