A32-05 Longitudinal Outcomes and Predictors of Refractory Type 2 Asthma Despite Treatment With Various Biologics From REGAIN, a Real-world Multi-center and Multimodal Study

Abstract Rationale In the era of numerous asthma biologics, an increasingly distinct subset of patients with asthma, despite evidence of type 2 (T2) disease, do not respond to multiple biologic classes that target T2 pathways. Their clinical course and predictors of biologic-refractory asthma remain poorly elucidated. The REal-world and Genomic data-based Asthma Insights through Network analysis (REGAIN) study—an 18-month prospective, observational, study with clinical, genomic, transcriptomic, and mobile health data—was designed to answer crucial knowledge gaps in the heterogeneity and pathogenesis underlying refractory T2 asthma. Methods REGAIN enrolled adults with asthma from specialty clinics at two academic centers according to T2 inflammation, asthma control, and treatment. T2 inflammation required evidence of blood eosinophil counts ≥300 cells/mcL, exhaled nitric oxide ≥50 ppb, or induced sputum/bronchoalveolar lavage eosinophilia ≥3%. The T2 Failed 2 Biologics group (T2 Failed) had to demonstrate T2 inflammation, history of failed response to ≥ 2 classes of biologics, and any level of control. The T2 Stable on Biologic group (T2 Stable) had to demonstrate T2 inflammation, current biologic therapy ≥4 months, and partly to well controlled status. Study visits occurred at 0-, 6-, and 18-months. Results Comparing T2 Failed (n = 40) and T2 Stable (n = 172) at baseline, T2 Failed had significantly higher proportions of obesity, gastroesophageal reflux disease, vocal cord dysfunction/laryngeal hypersensitivity, diabetes mellitus, lower educational status, and earlier age of asthma onset (all P .05). At 6- and 18-months, they had significantly worse asthma control and higher rates of exacerbations (all P ≤.001). At 6- and 18-month visits, most in T2 Stable had symptom control (71% and 74%, respectively) and were exacerbation-free between visits (80% and 79%, respectively). In contrast, for T2 Failed, only 24% and 13% had symptom control and 52% and 40% were exacerbation-free between visits at 6- and 18-months. In multivariate regression, at 18-months, controlling for race, ethnicity, gender, age, education, income, BMI, age of asthma onset, and smoking, T2 Failed remained a significant predictor for poor asthma control defined by ACT, GINA, and exacerbations (all (P.001). In these models, protective factors included white race (P=.04), non-Latino ethnicity (P=.03), and high income (P=.04). Conclusions Refractory T2 asthma—despite evidence of elevated T2 biomarkers, the use of different biologic classes, and ongoing specialty care—represents a persistently difficult-to-treat and high-morbidity group. Elucidating predictors may aid in earlier detection and inform whether repeated switching of T2-targeted biologics, dual biologics, or new agents targeting other key pathways may be more effective therapeutically. This abstract is funded by: Sanofi