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Pending and recently approved treatment options for patients with chronic obstructive pulmonary disease range from biologics to a triple-drug inhaler.
Pending and recently approved treatment options for patients with chronic obstructive pulmonary disease (COPD) range from biologics to a triple-drug inhaler. Here are four treatment changes to watch:
“Inflammation is an important component in the pathogenesis of both asthma and COPD,” says Michael Jacobs, PharmD, director of research development in the department of thoracic medicine and surgery at Temple University Lewis Katz School of Medicine. “The cell types involved in this inflammatory process have generally been considered to be different, with asthma being driven by eosinophilic inflammation and COPD being driven by neutrophils.”
However, it is now recognized that eosinophils can contribute to the daily symptom burden of some patients with COPD.
“Interleukin-5 (IL-5) is a cytokine that regulates eosinophil growth and recruitment, and plays a key role in many allergic diseases,” Jacobs says. “Hence, it has been considered a potential therapeutic target.”
Mepolizumab is a monoclonal antibody that has been directed against IL-5. The results of two randomized, placebo-controlled trials of the antibody for the treatment of COPD unresponsive to triple therapy were recently published in the New England Journal of Medicine.
“These studies demonstrate that mepolizumab given as a 100 mg. subcutaneous injection every four weeks for 52 weeks reduced the frequency of moderate or severe COPD exacerbations: a reduction of 1.40 exacerbations per year compared to a reduction of 1.71 per year with placebo,” Jacobs says.
Based on these results, GlaxoSmithKline has submitted an application to the FDA for the approval of mepolizumab for the treatment of COPD with elevated eosinophils unresponsive to triple therapy.
“The proportion of COPD patients who meet these clinical characteristics is unknown at this time,” Jacobs says. “Nonetheless, mepolizumab will provide a valuable treatment option for those patients who otherwise are poorly controlled.”
“Patients with mild disease and intermittent symptoms of COPD can be adequately managed with short-acting bronchodilators, such as albuterol or ipratropium,” Jacobs says. “However, as symptoms progress and become more chronic, longer-acting agents are recommended.”
These longer-acting drugs can be in the form of a long-acting beta-2 agonist (LABA), such as formoterol and salmeterol, or a long-acting antimuscarinic (LAMA) like tiotropium and aclidinium.
To further intensify therapy, combinations of a LABA and a LAMA are available; for example, Utibron from Sunovion, a combination of indacaterol and glycopyrrolate. “But some patients require the addition of an inhaled corticosteroid (ICS),” Jacobs says.
In September 2017, the FDA approved the first triple therapy (LABA, LAMA, ICS) in a single inhaler: Trelegy Ellipta from GlaxoSmithKline and Innoviva, containing fluticasone furoate, umeclidinium, and vilanterol, for maintenance of COPD.
“Because of the known compliance issues with inhalers, the availability of this triple combination should benefit a sizeable population of COPD patients,” Jacobs says. “Still, there are some potential concerns, such as the higher risk of pneumonia, associated with longer-term use of inhaled corticosteroids in the COPD patient population.”
The older oral agent roflumilast, which is a potent and selective inhibitor of the enzyme phosphodiesterase-4 in oral form, may soon show an increased demand, according to Fernando Martinez, MD, chief of the division of pulmonary and critical care medicine at Weill Cornell Medical College in New York City. “There is data under review that suggests that the medication is most likely beneficial in a very narrow population of COPD patients: those with chronic bronchitis, severe COPD, and a previous history of exacerbations,” Martinez says.
Martinez believes COPD patients most likely to benefit from roflumilast will be those with severe airflow obstruction, chronic bronchitis phenotype, and a hospitalization for a COPD exacerbation in the past year.
This is considered mostly experimental in the U.S. but is broadly used clinically in Europe. “I suspect, though, within the near future, that bronchoscopic approaches will begin to be used clinically in the U.S., albeit in a narrow group of severe COPD patients with favorable emphysema CT appearance,” Martinez says.
Overall, there is a growing movement to segment therapy for COPD patients to a precision-based therapeutic approach, says Martinez. “This will balance benefit with risk, and aid patients and likely decision making for their clinicians and payers. As such, therapies with limited benefit but higher risk and/or cost may be less likely to be clinically used,” he says.
Bob Kronemyer is a freelance writer based in Elkhart, Indiana, with an emphasis in healthcare and general business.