Comorbidities modify the phenotype but not the treatment effectiveness to mepolizumab in severe eosinophilic asthma

Background: Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities are needed to inform clinical practice. Objective: To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA. Methods: Patients enrolled in the Australian Mepolizumab Registry (n = 309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin-exacerbated airway disease, asthma-chronic obstructive pulmonary disease overlap (ACO), fungal sensitization, and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed. Results: Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range: 47%-77%), maintenance oral corticosteroid use (dose reduction: 4.2-13.3 mg/d), and improved symptom control (Asthma Control Questionnaire-5 score: 1.9-2.4 point reduction) and lung function (mean: 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1 second). Peripheral blood eosinophils were reduced (mean: 480-780 cells/μL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype. Conclusions: Mepolizumab treatment is associated with comparable clinical improvements in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.