Targeted therapy in eosinophilic chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a common and preventable airway disease causing significant worldwide mortality and morbidity. Lifetime exposure to tobacco smoking and environmental particles are the two major risk factors. Over the last decades, COPD has become a growing public health problem with an increase in incidence. COPD is defined by airflow limitation due to airway inflammation and small airway remodelling coupled to parenchymal lung destruction. Most patients exhibit neutrophil-predominant airway inflammation combined with an increase in macrophages and CD8+ T-cells. Asthma is a heterogeneous chronic inflammatory airway disease. The most studied subtypes is T2 high eosinophilic asthma, for which there are an increasing number of biologic agents developed. However, both asthma and COPD are complex and share common pathophysiologic mechanisms. They are known as overlapping syndromes as approximately 40% of patients with COPD present an eosinophilic airway inflammation. Several studies suggest a putative role of eosinophilia in lung function decline and COPD exacerbation. Recently, pharmacological agents targeting eosinophilic traits in uncontrolled eosinophilic asthma, especially monoclonal antibodies directed against interleukins (IL5, IL4, IL13) or their receptors, have shown promising results. This review examines data on the rationale for such biological agents and assesses efficacy in T2-endotype COPD patients.

Precision medicine in chronic obstructive pulmonary disease

“…They are associated with worse health status, and an increased risk of exacerbations and respiratory mortality [41,42] . Identifying IL-13 driven bronchitis opens the possibility of precision therapy with anti-IL-13 agents for these patients [43] …”

“…[ 41 , 42 ] Identifying IL-13 driven bronchitis opens the possibility of precision therapy with anti-IL-13 agents for these patients. [ 43 ]…”

Evolving Concept of Severe Asthma: Transition From Diagnosis to Treatable Traits

“… 72 The pathogenetic role of eosinophils is less clear in COPD than in asthma, but eosinophilic inflammation in COPD is associated with an increased risk of exacerbation, and a strategy to mitigate eosinophilic inflammation in patients with COPD reduces severe exacerbation. Although RCTs of T2 biologics in COPD have not demonstrated efficacy, mepolizumab reduces the rate of exacerbations in the subgroup of COPD patients with an elevated blood eosinophil level, 73 suggesting that eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway diseases.…”

Is it Time to Look Beyond Bronchodilators and Corticosteroids in Treating COPD?

“…The high percentage of patients with COPD who show a T2 (eosinophilic) inflammation explains the interest in evaluating the effects of anti-IL-5 mAbs [10]. There is evidence that mepolizumab, which blocks free IL-5, and benralizumab (an anti-IL-5Rα mAb) may reduce the rate of moderate and severe exacerbations in patients who have both COPD and higher levels of blood eosinophils [7,10].…”

“…The high percentage of patients with COPD who show a T2 (eosinophilic) inflammation explains the interest in evaluating the effects of anti-IL-5 mAbs [10]. There is evidence that mepolizumab, which blocks free IL-5, and benralizumab (an anti-IL-5Rα mAb) may reduce the rate of moderate and severe exacerbations in patients who have both COPD and higher levels of blood eosinophils [7,10]. Furthermore, two pivotal studies assessing dupilumaba mAb that targets IL4Rα thus inhibiting signaling of both IL-4 and IL-13, key drivers of T2 inflammation -in COPD patients with T2 inflammation (NCT03930732 and NCT04456673) are ongoing [10].…”