Chronic obstructive pulmonary disease (COPD) is responsible for considerable morbidity and mortality, affecting approximately 15 million persons in the United States and 65 million persons worldwide. In 2012, COPD was the third leading cause of death in the US. Emphysema is present in 25% of patients with COPD and in that population is associated with increased symptoms, a worse quality of life substantial costs, and increased mortality.1,2
There are ongoing efforts to find better therapies for this disease. At the American College of Chest Physicians 2015 meeting (CHEST 2015) in Montreal, a session discussing potential new treatments for COPD in phase II and III clinical trials was held. Following are highlights of several studies.
Inhaled combination therapies. Dr Jay Peters of University of Texas Health Science Center, presented data regarding improved inhaled combination therapies created using particle engineering. Dr. Peters and colleagues chose a combination of formoterol (4.5 microgram), budesonide (160 microgram) and tiotropium (9 microgram) prepared by an ultrarapid freezing phase followed by a thin film freezing technique. The technology puts the multidrug therapy in a single dry powder inhaler. Clinical trials assessing the effectiveness of this unique combination will follow.
Arformoterol. Professor James Donohue, MD, chairman of the board of the American Thoracic Society presented data on arformoterol, a long-acting β2-agonist (LABA), added to tiotropium. The agent has been shown to significantly improve outcomes in moderate-to-severe COPD as compared to tiotropium monotherapy or placebo. The study was a multicenter, randomized controlled trial with 841 patients followed for 1 year. The patients remained on standard COPD medications throughout the trial (excepting LABAs). Primary endpoints were respiratory death or COPD exacerbation-related hospitalizations and both were lower in the treatment group compared to placebo. Improvements in lung functions (FEV1) were small in patients already receiving tiotropium at baseline. There was no increase in incidence of adverse events with the addition of arformoterol.
QVA149. Dr. Edward Kerwin, medical director of clinical research institute in southern Oregon, presented a pooled analysis from studies demonstrating efficacy of the novel fixed-dose combination agent QVA149 (indacaterol/glycopyrronium or IND/GLY). The combined formulation afforded a significant improvement in lung function compared with placebo or either component of QVA 149 alone. Indacaterol (a LABA) and glycopyvrronium, a long acting-muscarinic antagonist (LAMA) are approved in 75 countries for the maintenance treatment of patients with moderate to severe COPD.
Dr Kerwin’s analysis included more than 2030 patients. Improvements in lung function were reported as post-dose FEV1 at 5 minutes on day 1; pre and post-dose trough FEV1 on day 85 and day 86 respectively; and peak FEV1during first 4 hrs post-dose on day 1 and day 85. There was a 109 mL increase in FEV1 at 5 minutes post-dose on day 1; a 207 mL increase of pre-dose trough FEV1 on day 85; and a 223 mL increase of post-dose trough FEV1 on day 86. The study concluded that twice daily IND/GLY 27.5 microgram/12.5 microgram is an effective treatment for patients with moderate to severe COPD. The agent is currently awaiting FDA approval.
Angiotensin receptor blockade. Finally, Dr Allison Lambert, from the department of pulmonology at Johns Hopkins presented a phase II trial showing the potential benefit of angiotensin receptor blockade in the treatment of COPD. In animal studies, losartan partially reversed impaired alveolar septation, preventing emphysema in mice.3 In another mouse model, losartan attenuated a cigarette smoking-induced increase in total lung capacity, prevented cigarette smoking-impaired elasticity changes, and blocked destructive airspace enlargement.4
The Hopkins group randomized 106 patients into losartan 100 mg daily versus placebo groups with follow up at 6 months and then at 1 year. CT scans were obtained at randomization and after 1 year to quantify the percent of emphysema and airway wall thickness. Spirometry, lung volumes, and DLCO were also obtained. Among patients with CT-defined emphysema, losartan had the potential to prevent disease progression. The group is planning a phase III trial with a larger number of patients.
COPD is a common condition seen in primary care but can be difficult to treat. Newer, effective medications will help clinicians and patients when they “hit a wall” with the paucity of therapeutic choices available today. Slowing the progression of the disease with losartan is also an attractive possibility; even more so as primary care is already comfortable with losartan so that learning curve might be mild.