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GlaxoSmithKline recently got a boost for fluticasone-furoate + vilanterol (Breo Ellipta), its new once-daily COPD maintenance inhaler. Patients with COPD randomized to Breo Ellipta (called Relvar Ellipta in Europe), instead of usual care, had 8% fewer exacerbations and no increased risk for serious adverse events over one year. GSK presented the data at the ERS international congress and published it simulatneously in the New England Journal of Medicine.
The Salford Lung Study had an interesting design: it was a year-long (2013-2014), open-label comparative effectiveness trial conducted in unselected patients recruited from 75 general practices around the town of Salford in the U.K. As such, it sidestepped a common criticism of COPD treatment trials: that highly restrictive enrollment criteria result in drugs' being approved without proven benefit in the (much sicker) patients in the community. The Salford study, by contrast, enrolled about half of the registered patients with COPD in the designated geographic area around Salford.
About 2,800 patients were randomized to receive either once-daily inhaled combination of fluticasone furoate 100 μg and vilanterol 25 μg or to usual care. They could continue a long-acting muscarinic antagonist (e.g. tiotropium) if they were already on one. Usual care was determined by the practicing physician. All recruited patients had experienced one or more COPD exacerbation in the past 3 years (average, 2 in the previous year) and were already taking regular maintenance inhalers. The patients were on average 67 years old, overweight (BMI 28), evenly split by gender, with an average FEV1 of 1.62 liters, and about 25% had cardiac disease.
The primary outcome was the mean annual rate of moderate or severe exacerbations, defined as any worsening of respiratory symptoms leading to treatment with antibiotics or systemic glucocorticosteroid, to hospital admission, or to scheduled or unscheduled hospital visits.
The rate of moderate to severe exacerbations was 1.64 over the course of the year in the usual care group, compared with 1.50 in the fluticasone furoate-vilanterol group. That's a 0.14 exacerbation per year absolute reduction, or a number needed to treat for one year of about 7 to prevent an exacerbation. There was no increase in pneumonia, death, or other adverse events in the treatment group.
Unblinded (open label) studies are inherently more susceptible to bias. More patients taking fluticasone-furoate + vilanterol did choose to switch back to their more familiar treatments than the other way around. However, a priori, the high observed crossover would be expected to reduce any observed benefit of fluticasone-furoate + vilanterol. Many patients (22%) also had a diagnosis of asthma in addition to COPD, a common co-diagnosis in the community that would have led to exclusion from traditional clinical trials for COPD.
Authors, some of whom are GSK employees, lauded their trial design and its applicability to real-world practice:
For any new treatment, safety and efficacy randomized, controlled trials are essential, but they are carried out in carefully selected populations, from which patients with coexisting conditions are excluded, and represent less than 10% of patients with COPD. [Patients in the Salford study] were largely unsupervised over the yearlong period, which allowed important factors in usual clinical care, such as adherence, frequency of dosing, and persistence of good inhaler technique, to come into play.
The benefits shown for fluticasone-furoate + vilanterol in a large group of unselected people with COPD -- outside the Japanese garden of a tightly controlled phase III clinical trial -- are persuasive. It's unclear why the drug was superior, but increased adherence with the once daily inhaler compared to usual care is possible. Expect heavy airplay of these results by GSK and a push to include Breo Ellipta in future guidelines for care of COPD.
Read more: Effectiveness of Fluticasone Furoate–Vilanterol for COPD in Clinical Practice. N Engl J Med 2016; 375:1253-1260