Single-Inhaler Triple Therapy Reduces Composite AE Risk vs Dual Therapy in COPD

Single-inhaler triple therapy is associated with a favorable benefit-risk profile compared with dual therapy for patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations, according to research presented at the American Thoracic Society (ATS) 2021 International Conference, held virtually from May 14 to May 19, 2021.

Early results of the IMPACT trial (ClinicalTrials.gov Identifier: NCT02164513) showed that fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) single-inhaler triple therapy led to a significant reduction in exacerbation rates and all-cause mortality compared with UMEC/VI in COPD. Despite this, concerns have been raised regarding an increased pneumonia risk associated with inhaled corticosteroid-containing regimens, as well as cardiovascular effects associated with dual bronchodilation. To further clarify the benefit-risk profile of FF/UMEC/VI vs FF/VI and UMEC/VI in the study population, researchers evaluated composite adverse event outcomes.

IMPACT — a 52-week, randomized, double-blind, multicenter study — compared FF/UMEC/VI 100/62.5/25 µg with FF/VI 100/25 µg and UMEC/VI 62.5/25 µg in a population of patients aged 40 years and older with symptomatic COPD and either forced expiratory volume in 1 second (FEV₁) <50% predicted and at least 1 moderate or severe exacerbation, or FEV₁ 50% to <80% predicted and at least 2 moderate or at least 1 severe exacerbation.

Researchers analyzed time-to-first composite event, defined as on-treatment severe exacerbation or cardiovascular adverse events of special interest (AESI) and on-treatment pneumonia AESI, all resulting in hospitalization or death, or on-treatment death from any cause.

The total cohort included 10,355 patients (FF/UMEC/VI n=4151; FF/VI n=4134; UMEC/VI n=2070). In total, 16%, 15%, and 17% of patients in each group, respectively, experienced composite events. The probability of experiencing event before the 1-year mark with each treatment was 16.7%, 17.5%, and 19.1%, respectively.

Treatment with FF/UMEC/VI significantly reduced the risk of composite events vs UMEC/VI by 16.5% (95% CI, 5.0%-26.7%). Point estimates for risk reduction also favored FF/UMEC/VI over FF/VI (6.2% reduction) and FF/VI over UMEC/VI (11.1% reduction). However, these differences were not statistically significant.

“FF/UMEC/VI significantly reduced the risk of a composite adverse event vs UMEC/VI and numerically reduced the risk vs FF/VI, demonstrating a favorable benefit-risk profile [for] once-daily FF/UMEC/VI triple therapy compared with dual therapy in patients with symptomatic COPD and a history of exacerbations,” the researchers concluded.

Disclosure: This research was supported by GlaxoSmithKline. Please see the original reference for a full list of disclosures.

Reference

Wells JM, Bhatt SP, Carr TF, et al. An analysis of the IMPACT trial assessing single-inhaler therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI using a composite adverse event outcome in patients with COPD. Presented at: the American Thoracic Society (ATS) 2021 International Conference; May 14-19, 2021. Abstract A2240.