D102-07 When Biologics Are Not Enough: Characteristics of Asthma Patients Who Continue to Exacerbate

Abstract Rationale Monoclonal antibody therapies (biologics) significantly reduce exacerbations in patients with asthma that remains poorly controlled despite optimized inhaled therapy. However, some individuals continue to experience exacerbations following initiation of the appropriate biologic. This seeming lack of effectiveness can be due to various factors that may be patient-, disease-, and medication-related. We sought to evaluate factors contributing to continued exacerbations on biologics in patients with moderate-severe asthma. Methods We leveraged data from 1,449 patients with severe asthma who initiated one of the six biologics currently approved for the treatment of asthma and were seen in a tertiary center in the US between 2010 and 2025. We compared the baseline clinical, demographic, and laboratory characteristics of patients who had low-frequency (2 exacerbations in the year following therapy initiation) vs high-frequency (≥2) on-treatment exacerbations. Likewise, we identified factors associated with the probability of switching from a high-frequency group before biologic treatment to a low-frequency group post-biologic and vice-versa. Results Of the 1449 patients, 529 (36.5%) initiated omalizumab, 408 (28.2%) dupilumab, 322 (22.2%) mepolizumab, 115 (7.9%) benralizumab, and 75 (5.2%) tezepelumab. Mean baseline exacerbation count was 2.0 (SD 2.5) in the year prior to biologic initiation and baseline total IgE and eosinophil counts were 521 IU/ml (SD 1130) and 410 cells/microliter (SD 611), respectively. At baseline, 813 (56.2%) of patients were low-frequency (2) exacerbators and 636 (43.8%) as high-frequency (≥2) exacerbators. Following biologic initiation, 325 (51.1%) of the high-frequency exacerbators became low-frequency exacerbators, with 311 (48.9%) continuing to be high-frequency exacerbators. Patients who remained high-frequency exacerbators despite treatment were more likely to be Hispanic (5.5% vs. 3.8%, p = 0.05), urban-dwelling (23.7% vs 13.6%, p 0.001), have public insurance (37.5% vs 30.7%, p = 0.012), have comorbid COPD (9.6% vs 22.6%, p 0.001), and had lower baseline eosinophil counts (344 vs 484 cells/mcl). Patients with high-frequency exacerbations requiring admissions (≥2) after initiating biologic therapy were more likely to be urban-dwelling, have a BMI ≥30, Black, have comorbid COPD and less likely to have CRSwNP. Conclusions In this single but large health-system study, multiple socioeconomic factors associated with exacerbations before biologic therapy were also associated with continued exacerbations on biologics. Our findings highlight the importance of identifying and addressing these factors in patients who continue to have frequent exacerbations on biologics in order to maximize the benefits of these therapies in all patients with poorly controlled asthma. This abstract is funded by: None