AUSTIN, TEX.– Once daily combination treatment with umeclidinium and vilanterol was more effective than twice-daily combination treatment with fluticasone and salmeterol in patients with moderate to severe chronic obstructive pulmonary disease in two 12-week double-blind, parallel-group double-dummy studies.
In the two multicenter studies, 706 and 697 patients, respectively, were randomized to receive either 62.5 mcg of the long-acting muscarinic antagonist (LAMA) umeclidinium and 25 mcg of the long-acting beta-2 agonist (LABA) vilanterol – a recently approved combination bronchodilator maintenance treatment for COPD – or a combination of 250 mcg of the inhaled corticosteroid (ICS) fluticasone and 50 mcg of the LABA salmeterol, which is also indicated as a maintenance therapy for COPD.
The patients in the LAMA/LABA groups, who were treated once daily for 12 weeks, had significantly greater improvements on all lung function measures, compared with those in the ICS/LABA groups, who were treated twice daily, Dr. James F. Donohue of the University of North Carolina at Chapel Hill reported at the annual meeting of the American College of Chest Physicians.
In the first study, the improvement from baseline to day 84 (the primary study endpoint) in 0- to 24-hour weighted mean forced expiratory volume in 1 second (FEV1) was 165 mL for the LAMA/LABA group, compared with 91 mL in the ICS/LABA group. In the second study, the improvement in the two groups was 213 mL and 112 mL.
The LAMA/LABA combination also improved trough FEV1 on day 85 by 82 mL and 98 mL more than did the ICS/LABA combination in the two studies, respectively.
Both combinations provided clinically meaningful improvements in dyspnea and quality of life scores, Dr. Donohue said.
Adverse events occurred during treatment in a similar proportion of patients in both treatment groups in both studies: 26% and 27% in the LAMA/LABA and ICS/LABA patients in the first study, and 30% and 31%, respectively, in the second study. The most common adverse events were headache and nasopharyngitis.
In the first study, serious adverse events occurred in 2% of the LAMA/LABA patients and 3% of ICS/LABA patients, and in 3% and 4% of patients in the second study.
One death occurred in the ICS/LABA group in the first study, but it was not considered study related. Five deaths occurred in the second study, including two in the LAMA/LABA patients and three in the ICS/LABA patients. One of the deaths in the ICS/LABA group was because of pneumonia and was reported as drug related by the investigator.
No new safety signals were detected in these studies, Dr. Donohue said.
Patients in both studies had FEV1 between 30% and 70%, and had not experienced a COPD exacerbation within the previous year. The LAMA/LABA therapy was delivered via Ellipta inhaler, and the ICS/LABA therapy was delivered via Diskus inhaler.
The Food and Drug Administration approved umeclidinium/vilanterol combination therapy (Anoro Ellipta) in December 2013, the first LAMA/LABA therapy approved in the United States. Dr. Donohue and his colleagues conducted the pivotal regulatory trial of the drug combination, which was published in July 2013 (Respir. Med. 2013;107:1538-46).
The current trials represent an effort to determine where the treatment fits into the armamentarium for treating patients with COPD, he said.
The “really robust findings as befits two bronchodilators” suggest umeclidinium/vilanterol combination therapy is an effective treatment option that provides greater lung function than fluticasone/salmeterol for moderate to severe COPD in patients with infrequent exacerbations, Dr. Donohue said.
GSK, which developed the umeclidinium/vilanterol combination product with Theravance, funded the studies. Dr. Donohue reported receiving consultant fees and/or serving on an advisory committee for Almirall, AstraZeneca, Boehringer Ingelheim, Dey, Elevation Pharmaceutical, Forest Laboratories, GlaxoSmithKline, Novartis, Pearl Pharmaceuticals, Pfizer, and Sunovion. He has also served as a member of drug safety monitoring boards for the National Institutes of Health, Novartis, Otsuda, Pearl, and Teva.