Reduced Effectiveness of Anti-IgE Treatment Among Adults with Severe Asthma with Older Age of Asthma Onset: Results from the CHRONICLE Study

Purpose: Younger age of asthma onset (AAO) has been associated with an allergic phenotype, whereas eosinophilic phenotypes have been associated with older AAO. In randomized trials, biologic efficacy among adults with severe asthma (SA) has varied by age at asthma onset. To determine whether these associations observed in trials apply to real-world outcomes, this study examined biologic effectiveness by AAO and biologic class in a large, real-world cohort. Patients and methods: CHRONICLE is an ongoing, real-world study of US adults with subspecialist-treated SA receiving biologics, maintenance corticosteroids, or who are uncontrolled on high-dosage inhaled corticosteroids with additional controllers. Patients enrolled between February 2018 and February 2022 who initiated a biologic for SA and had complete data for analysis were included. A locally estimated scatterplot smoothing (LOESS) analysis was used to plot the relationship between percentage exacer- bation rate reduction and AAO by biologic class. Results: Of 578 patients with complete data, 198, 149, and 231 were diagnosed with asthma at age <18, 18-39, and >= 40 years, respectively. Across subgroups, patients were predominantly White (72-78%), female (67-73%), and commercially insured (54-71%). In the LOESS analysis, exacerbation rate reductions were similar for anti-IgE and anti-IL-5/5R and anti-IL-4R subgroups with younger AAO, but the exacerbation rate reduction diminished for patients with older AAO receiving anti-IgE therapy, particularly with asthma onset age >= 40 years. Conclusion: Clinicians should consider age of onset in biologic treatment decisions, given reduced effectiveness of omalizumab in patients with asthma onset at age >= 40 years.