A32-24 Baseline Characteristics and Prospective Outcomes of Symptom-Controlled Type 2 Low Compared to Type 2 High Asthma in the Real World and Genomics Based Asthma Insight Through Network Analysis (REGAIN) Cohort

Abstract Introduction T2 low (T2L) asthma is a group with unmet treatment needs with limited understanding of patient characteristics and longitudinal clinical course. T2L asthma has been defined using variable cutoff levels of FeNo and blood eosinophil counts (BEC). In studies where gene expression is assessed in sputum, T2L clinical phenotypes determined by biomarkers did not correlate with transcriptomes, and oral corticosteroid (OCS) use impacted biomarkers and gene expression. Here we describe baseline demographic and prospective exacerbation rates of T2L and high (T2H) participants with asthma symptom control at enrollment in REGAIN, a retrospective and prospective real world asthma cohort. Methods REGAIN is a cohort (n = 676) from 2 specialty clinic sites that enrolled prespecified subsets of asthma patients (ClinicalTrials.gov study #NCT06623435). T2H had FeNO ≥ 50 ppb or BEC ≥ 300/uL and T2L had FeNO ≤ 25 ppb, and BEC ≤ 200/uL on review of all biomarkers in the electronic medical record (EMR) prior to enrollment. Participants were on GINA Step 1-5 treatment excluding asthma biologics and chronic OCS. We compared characteristics of T2L and T2H participants with asthma control test (ACT ≥ 20) at enrollment given the groups’ dissimilarity in asthma markers with comparable therapeutic options. We also examined exacerbation events prospectively over 18 months. We generated P-values from two-sided Fisher’s exact test for categorical variables and Kruskal-Wallis test for numeric variables. T2L and T2H status in REGAIN participants was supported by baseline gene expression using transcriptomics of nasal epithelial brushings. Results REGAIN enrolled T2L (n = 152) and T2H (n = 197) participants. Asthma symptom control (ACT 20) at enrollment was noted in T2L (n = 64) and T2H (n = 169) participants. Age, biological sex, race, BMI, age of diagnosis and duration of asthma, and most comorbidities were similar between T2L and T2H groups. Fewer T2L enrolled from National Jewish Health had ACT 20 (p = 0.001) and were ethnic minorities (p = 0.011). T2H and T2L groups had similar GINA Step treatment at baseline. Over 18 months, T2H had more exacerbations requiring oral steroids, ED visits, and hospitalizations (p = 0.002, 0.035, 0.053, respectively). As expected, T2H had higher mean BEC (289.63 ± 233) versus T2L (107.81 ± 59, p = 0.0001) and mean FeNO of 36.3 ± 37 versus 14.1 ± 5 (p = 0.0001). Conclusions Symptom controlled T2L and T2H asthma participants categorized by historical FeNo and BEC and supported by nasal transcriptomics were not distinguishable by baseline characteristics. T2H participants had a higher risk clinical course on longitudinal follow-up. This abstract is funded by: Sanofi