麻豆传媒

SAN ANTONIO -- Treatment with the triple, single-inhaler therapy Trelegy Ellipta significantly reduced the annual rate of moderate-to-severe and severe exacerbations in patients with both reversible and nonreversible chronic obstructive pulmonary disease (COPD) participating in the IMPACT trial.

In new findings from the GlaxoSmithKline trial, reported here at the patients on the triple therapy also had improvements in overall lung function and quality of life (QoL) -- regardless of disease reversibility -- compared with patients taking dual inhaled corticosteroid/long-acting beta agonist (ICS/LABA) or long-acting muscarinic agonist (LAMA)/LABA therapies.

The GlaxoSmithKline ICS/LAMA/LABA combination treatment is the first fixed-dose, triple therapy approved in the U.S. for COPD.

James Donohue, MD, of the University of North Carolina in Chapel Hill, who was not involved in the post-hoc analysis presented here, told 麻豆传媒 that the fact that patients with baseline nonreversible COPD responded with an improvement in lung function is noteworthy.

"It speaks to important positive interactions with the three agents," he said. "And the impact on quality of life and exacerbation hospitalizations as noted in these follow-up IMPACT studies is also encouraging."

Donohue said triple therapy should now be considered a first-line treatment for COPD patients with exacerbations or GOLD D-stage disease.

IMPACT was a randomized, double-blind, parallel-group, 1-year global study that initially included 10,355 COPD patients with a history of moderate-to-severe exacerbations in the prior year.

At screening, patients were categorized as "reversible" when a difference between pre- and post-albuterol assessment of forced expiratory volume in 1 second (FEV₁) of ≥12% and ≥200 mL was observed.

The effect of baseline reversibility on treatment response with the triple therapy -- fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) 100/62.5/25 mcg -- was compared with two dual therapies, FF/VI and UMEC/VI.

At screening, 18% of patients demonstrated reversibility. There was a statistically significant reduction in the rate of on-treatment moderate or severe exacerbations with the triple therapy versus UMEC/VI in reversible (40% reduction, 95% CI 28%-50%) and non-reversible patients (21% reduction, 95% CI 14%-28%).

Compared with UMEC/VI, the reduction in the severe exacerbation rate with the triple therapy was 44% (95% CI 14%-63%) in reversible patients and 31% (95% CI 17%-44%) in non-reversible patients.

Treatment with the triple therapy also led to a reduction in the risk of time-to-first moderate-to-severe exacerbation:

• FF/UMEC/VI 25.6%, 95% CI 11.0%-37.9%
• UMEC/VI 13.6%, 95% CI 6.2%-20.5%

And in the risk of time-to-first severe exacerbation:

• FF/UMEC/VI 32.8%, 95% CI 2.8-53.5%
• UMEC/VI 23.5%, 95% CI 9.7%-35.2%

Greater improvement with the triple therapy compared with UMEC/VI was observed in lung function (change from baseline in trough FEV₁ at 1 year: 76 mL and 49 mL, respectively), and in QoL as measured by the St. George Respiratory Questionnaire (odds of questionnaire responders at 1 year: 1.38 and 1.41, respectively). These differences were independent of reversibility status at screening (all P values<0.05).

Statistically significant improvements of FF/UMEC/VI over FF/VI were observed on all endpoints in non-reversible patients and on the moderate/severe exacerbation rate and lung function endpoints for reversible patients. The triple therapy did not reduce the rate of severe exacerbations over FF/VI in reversible patients.

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