New COPD Treatments Being Developed

BY DOUG BRUNK
Elsevier Global Medical News

HONOLULU – Current interventions for chronic obstructive pulmonary disease leave many patients with unmet needs, said Dr. Nicola A. Hanania, FCCP.

“We know from large clinical trials that current pharmacotherapies do not change the natural history of COPD, and many patients remain symptomatic with current therapies,” Dr. Hanania, director of the asthma clinical research center at Baylor College of Medicine, Houston, said at the annual meeting of the American College of Chest Physicians.

Inadequate adherence to therapy “is a major cause of poor clinical outcomes in the treatment of COPD,” he said. The cost, compliance, and safety of certain agents are issues “that we cannot ignore.”

When considering a therapy for COPD, clinicians should factor in components of COPD beyond bronchoconstriction, he advised, including mucociliary dysfunction, structural changes in the airway and the lung, systemic components, and airway inflammation. “We also have to look at outcomes other than lung function including exacerbations, activity limitation, and symptoms of dyspnea,” he said. “We are no more satisfied with just a drug that improves lung function but does nothing for the patient-reported outcomes.”

Dr. Hanania’s “wish list” for an ideal COPD therapeutic option in the future is one that addresses the multiple components and phenotypes of COPD. He said he would like to see drugs that blunt proinflammatory cells and molecules known to be involved in COPD. Agents should be well tolerated and compatible with other therapies for COPD and comorbid conditions, be simple to administer, and have the potential to improve patient adherence, he added.

Treatment approaches being studied include novel formulations of existing medications, such as the combination of ultralong-acting beta₂ agonists and long-acting antimuscarinics. Other agents in “development include bifunctional muscarinic antagonist–beta₂-agonists and combinations of once-daily long-acting beta₂-agonists and inhaled corticosteroids.

However, perhaps the most promising pharmacotherapies will be novel agents aimed at reducing local and systemic inflammation. “We know that COPD is an inflammatory disease, so we need drugs that can target inflammation right from the very beginning,” Dr. Hanania explained. “Inhaled steroids are important, but they’re not as effective in COPD as they are in asthma.”

Phosphodiesterase type 4 inhibitors are currently being studied in COPD. These agents reduce the activity of neutrophils, macrophages, and CD8-positive T lymphocytes, as well as the expression of cytokines and other inflammatory mediators. Currently, the only phosphodiesterase type 4 inhibitor approved in the United States for use in patients with COPD is roflumilast (Daliresp). Several others are in development.

Because they target airway inflammation, p38 mitogen-activated protein kinase inhibitors are also being studied in COPD patients. However, so far clinical trials have found potential problems related to systemic side effects and toxicity, “indicating that it is probably necessary to deliver these drugs by inhalation to reduce systemic exposure,” Dr. Hanania said.

He concluded his presentation by noting that certain medications used to treat comorbidities in COPD may have beneficial effects on COPD outcomes. These include statins, ACE inhibitors, beta-blockers, peroxisome proliferator– activated receptor agonists, and macrolides. The National Heart, Lung, and Blood Institute COPD Clinical Research Network is currently conducting a prospective randomized controlled trial in 1,126 patients with severe COPD randomized to daily simvastatin (40 mg) vs. placebo for at least 1 year. Furthermore, a recent study showed that daily azithromycin significantly reduced exacerbations in high-risk patients.

Dr. Hanania disclosed that he has received funds from the National Institutes of Health, the American Lung Association, GlaxoSmithKline, Boehringer Ingelheim, Sunovion, Novartis, Pfizer, Forest Pharmaceuticals, Dey Pharmaceuticals, and AstraZeneca.

COMMENTARY
Dr. Darcy Marciniuk, FCCP, comments: COPD has recently overtaken stroke to become the third leading cause of death in the United States, and barriers to optimal clinical care are abundant. Our patients continue to suffer. But as outlined by Dr. Hanania, many new potential therapies are being investigated – there are reasons to be hopeful the future holds exciting breakthroughs in COPD management.