Abstract Rationale IL-4 and IL-13, key and central drivers of type 2 inflammation, contribute to mucus hypersecretion via promotion of goblet cell differentiation, excess mucin (MUC5AC) production, and associated mucociliary disruption, leading to poorer disease outcomes, including mucus plug formation, in patients with COPD. The phase 3 BOREAS and NOTUS trials demonstrated that dupilumab, blocks IL-4 and IL-13 signaling, reduces moderate or severe exacerbations and improves lung function, disease symptoms, and quality of life (QoL) in patients with COPD and type 2 inflammation. Recently, VESTIGE study confirmed that dupilumab reduces mucus plugs and improves small airway function. The phase 4 AEOLUS study will evaluate the effect of dupilumab on airway inflammation, resistance, and remodeling, including mucus plugging, and its association with improvements in exacerbations, lung function, symptoms, and QoL in patients with moderate-to-severe COPD and type 2 inflammation. Methods AEOLUS (NCT07053423) is a multinational, randomized, double-blind, placebo-controlled, parallel-group, phase 4 study in patients aged 40 − 85 years with moderate-to-severe COPD with a post-bronchodilator FEV1/FVC ratio ≤0.70 and post-bronchodilator percent predicted FEV1 of ≥ 30% and 80%, on triple (inhaled corticosteroids ICS, long-acting β2-agonist, and long-acting muscarinic antagonist) or dual therapy (if ICS are contraindicated), with type 2 inflammation (blood eosinophils ≥300 cells/µL at screening or blood eosinophils ≥150 cells/µL at screening and a history of blood eosinophils ≥300 cells/µL in the previous year), a history of high exacerbation risk (defined as an exacerbation history of ≥ 2 moderate or ≥ 1 severe exacerbations within the year prior to the study), and a computed tomography (CT) mucus plug score ≥3 at screening. Patients with a prior or current diagnosis of asthma will be excluded. Approximately 218 patients will be randomized (2:1) to dupilumab 300 mg or matched placebo every 2 weeks for 24 weeks. Results The primary outcome will be change from baseline to Week 24 in lung mucus score (range 0 − 18; higher scores indicate greater mucus burden and mucus plugging). Secondary outcomes include change from baseline to Week 24 in mucus volume and trimmed distal airway wall thickness measured by high-resolution computed tomography (HRCT), and the difference in airway resistance from R5 to R20 and reactance area (AX) measured by forced oscillation technique (FOT). Safety outcomes, including treatment-emergent adverse events, will also be assessed. Conclusions The AEOLUS study will evaluate the effect of dupilumab on mucus plugging and airway remodeling using HRCT and FOT techniques in patients with moderate-to-severe COPD and type 2 inflammation. This abstract is funded by: Sanofi and Regeneron Pharmaceuticals Inc.
Bhatt et al. (Fri,) studied this question.