Jim Kling

October 26, 2014

AUSTIN, Texas — In two studies of patients with moderate to severe chronic obstructive pulmonary disease (COPD), patients receiving the once-daily combination of umeclidinium and vilanterol (Anoro Ellipta, GlaxoSmithKline) scored higher on lung function tests than those receiving the twice-daily combination of fluticasone and salmeterol (Advair Diskus, GlaxoSmithKline).

"We wanted to see how some of the other combinations compare," James Donohue, MD, professor of medicine at the University of North Carolina School of Medicine in Chapel Hill, who presented the research here at CHEST 2014, told Medscape Medical News.

Both combinations are approved by the US Food and Drug Administration for maintenance therapy of COPD.

The once-daily combination consists of a long-acting muscarinic antagonist and a long-acting inhaled beta-2 agonist, and is the only such combination currently available in the United States.

The combination of indacaterol and glycopyrronium bromide (Ultibro Breezhaler, Vectura Group PLC) has been approved in Europe, and other combinations are on the way in the United States.

Because combinations of muscarinic antagonists and inhaled beta-2 agonists are new, it is important to determine which patients are most likely to benefit from them. "Physicians don't know how to use them. We're trying to put them in their place, to determine what patients would benefit most," said Dr Donohue. There has also been some concern that the fluticasone and salmeterol can increase the risk for pneumonia.

The researchers conducted two 12-week trials of patients with a forced expiratory volume in 1 second (FEV₁) after salbutamol therapy of 30% to 70% of predicted values.

All patients were at least 40 years of age, had moderate to severe COPD, and had a dyspnea score above 2 on the modified Medical Research Council scale. Patients were excluded if they had at least one documented exacerbation that required oral corticosteroids, antibiotics, or hospitalization in the previous year.

In both studies, patients were randomly assigned to once-daily umeclidinium 62.5 μg and vilanterol 25.0 μg delivered with the Ellipta inhaler or to twice-daily fluticasone 250.0 µg salmeterol 50.0 µg delivered with the Diskus inhaler.

On day 84, improvement in FEV₁ was greater with the umeclidinium and vilanterol combination than with the fluticasone and salmeterol combination.

On day 85, the improvement in trough FEV₁ was also better with the umeclidinium and vilanterol combination.

Table. Improvement With the Umeclidinium and Vilanterol Combination

Improvement Study 930, mL (n = 706) Study 951, mL (n = 697) P Value
FEV1 74 101 <.001
Trough FEV1 82 98 <.001

 

There was one death in the fluticasone and salmeterol group in study 930, but it reportedly was not related to the drug. In study 951, there were two deaths in the umeclidinium and vilanterol group and three in the fluticasone and salmeterol group, one of which was from pneumonia and was drug-related.

"At the end of the day, the weighted mean of FEV₁ was greater by a substantial amount in the umeclidinium and vilanterol group," said Dr Donohue. "There was also a greater effect on FEV₁ trough in both studies. As far as quality of life and dyspnea, both combinations were very close. Both had good effect, but there was no significant difference. It's a little surprising because I would have thought patients would have perceived the differences in FEV₁."

He said, "This could be positioned for first-line therapy for patients with a lot of symptoms, pretty good lung function, and no exacerbations. I wouldn't use this in people with frequent exacerbations."

The data are compelling, and the umeclidinium and vilanterol combination is promising, said Samiran Patel, MD, a pulmonologist in the Saint Luke's Health System in Kansas City, Missouri, and critical care director at the system's Overland Park Hospital, who attended the session. The fact that the combination is taken once daily could increase compliance.

He expressed concern, however, over the short length of the trial. Depending on the time of year that the trial was run, there could have been weather effects. "Winter weather is harder on COPD patients, especially in North America," he explained.

Dr Patel does not expect to change his practice on the basis of the results. Instead, he will wait until more safety data have accumulated. He is also concerned about cost, because the newer medication is likely to have a higher price tag and might not be covered by insurance. "I have to be a patient advocate in terms of cost, and the way the healthcare reforms are now, they require that this is consciously considered in our decision making," he said.

Dr Patel has disclosed no relevant financial relationships. Dr Donohue has received consultant fees, speaker bureau fees, or advisory committee fees from Almirall, AstraZeneca, Boehringer Ingelheim, Dey, Elevation Pharmaceuticals, Forest Laboratories, GlaxoSmithKline, Novartis, Pearl Pharmaceuticals, Pfizer, and Sunovion; and has served as a member of Drug Safety Monitoring Boards for the National Institutes of Health, Novartis, Otsuda, Pearl, and Teva.

CHEST 2014: American College of Chest Physicians Meeting: Abstract 1991492. Presented October 26, 2014.

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