Identification of biologic-responsive phenotypes in elderly people with eosinophilic asthma

Background: Asthma in the elderly is not as well studied as in younger age groups. Age-related immunosenescence may result in diminished TH2 inflammation, which raises a question about whether asthma in elderly patients responds well to anti-TH2 asthma biologics. Objective: We sought to determine whether asthma in elderly people has different TH2 biomarkers and clinical features compared to nonelderly people, and if disease in the 2 age groups responds differently to anti-TH2 biologics. We also aimed to identify treatment-responsive phenotypes with clinical and biomarker features that could be used to predict best response to biologics. Methods: A retrospective chart review was conducted for 56 patients (30 elderly [age ≥62 years] and 26 nonelderly [ages 18-59 years] subjects) with severe asthma treated with dupilumab or benralizumab. Differences in baseline characteristics and response to treatment were analyzed. A hierarchical cluster analysis was also performed to identify treatment-responsive phenotypes. Significance threshold was P = .05 for all analyses. Results: Baseline characteristics and TH2 biomarkers (blood eosinophil level, total IgE, aeroallergen sensitivity) were similar between elderly and nonelderly subjects. The disease in both groups responded well to biologics (improvement in ACT scores, decreased exacerbations, decreased need for prednisone), but no significant response difference was found based on age groups. Cluster analysis identified 3 phenotypes, as follows: cluster 1, youngest age, moderate eosinophil levels, lowest total IgE, few environmental allergies, and least response to biologics; cluster 2, intermediate age, lowest eosinophil level, highest IgE level, many environmental allergies, and an intermediate response to biologics; and cluster 3, oldest ages, highest eosinophil levels, high total IgE, few environmental allergies, and best response to biologics. These results confirm trends seen in another study utilizing cluster analyses showing that subjects with highest levels of IgE and eosinophils responded better to biologic treatment for asthma. Conclusion: Elderly people with asthma should be considered for biologic therapy no differently than younger people. There may be subgroups of patients with different biologic responses based on age, allergenicity, IgE, and eosinophil levels that could be used to predict treatment response.