Treatment of Chronic Obstructive Pulmonary Disease : – Is the Selective Phosphodiesterase Inhibitor Ensifentrine a Safe and Effective Adjunctive Treatment for COPD?

Background Chronic Obstructive Pulmonary Disease (COPD) is a major chronic disease that affects one in ten people globally. It is an inflammatory disease in the lungs and lower airways, causing obstruction due to swollen mucous membranes, fibrotic scarring, mucus and a collapse of the lung and airway suspension system that inhibits normal airflow. Major symptoms seen in COPD are breathlessness, mucous cough and fatigue. Risk factors are among others high age, smoking, infectious diseases, air pollution, passive smoking, undertreated asthma and exposure to dust, gas and smoke. Often the same patients also have cardiovascular diseases. COPD is progressive, but the progression can be slowed down with the right treatment. It is also partly preventable. The pharmacological treatment varies depending on symptoms and how far the COPD has progressed, but the focus is mostly on inhaled drugs. Inhaled bronchodilators, called long-acting muscarinic antagonists (LAMA) and long-acting beta 2-receptor agonists (LABA), give expansion of the airways and are often used. Exacerbation-prone patients can be treated with inhaled corticosteroids (ICS), among others. Still, patients with remaining breathlessness despite LAMA and LABA do not have any good pharmacological options in Europe today. Ensifentrine, a small molecule and a new drug with both anti-inflammatory and bronchodilating effects, was 2024 approved for treating COPD in the USA.Objective This thesis aimed to examine and conclude about ensifentrine’s efficacy and safety regarding treating COPD-associated breathlessness.Method By searching, selecting and analysing articles with randomised controlled studies from PubMed this was exercised as a literature study.Results Five articles including four studies were reviewed. Ensifentrine was used alone or in different combinations: combined with ICS, LABA or LAMA alone, or ICS paired with LABA or LAMA. Doses between 0,375 mg and 6 mg were tested, all inhaled by a nebulizer twice daily. The studies ran for 4–48 weeks, comparing lung function, symptom improvement, health-related quality of life and adverse effects. Also some improvements were analysed regarding clinical significance. The participants were at least 400 in each study, they were 40–80 years old and all diagnosed with COPD. Adverse effects were as rare in the treated participants as for those given placebo. There was a varied but clear improvement in the participant’s lung function, especially with the 3 mg dose. Since the lung function is correlated with the progression of COPD, it also can be said to affect breathlessness. An improvement in breathlessness was also evident, with the results of several measurements reaching clinical significance. All of the studies are closely tied to the developer of ensifentrine, and the studies do not combine ensifentrine with other drugs in the way that would be most relevant according to the recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD). However, the results are still considered legit and applicable.Conclusion Ensifentrine is a safe and effective drug for treating breathlessness in COPD, both in that, it shows an improvement of lung function which may ease breathlessness long term, and in that it improves breathlessness in itself.