Abstract Rationale T2 inflammation is the underlying pathology for more than 80% of patients with severe asthma, which can lead to recurring symptoms and unpredictable exacerbations. IL-4, IL-5, and IL-13 are core cytokines in T2 inflammation that orchestrate multidirectional effects on immune and structural cells. Blood eosinophil count (BEC) ≥150 cells/µL is a well-established prognostic and predictive biomarker used to identify patients with a T2 inflammatory phenotype as well as those who may benefit from biologic therapy. This post hoc analysis assessed the relationship between BEC and serum T2 cytokine (IL-4, IL-5, and IL-13) levels in patients with severe asthma enrolled in the SWIFT-1/-2 Phase III trials of depemokimab; the first ultra-long-acting biologic, with enhanced IL-5 binding affinity, high potency, and an extended half-life, enabling sustained suppression of T2 inflammation with twice-yearly dosing in patients with asthma. Methods Baseline BEC from patients with asthma (N = 762; SWIFT-1/-2) and serum IL-4, IL-5, and IL-13 levels (assessed using MSD S-plex assays) from patients with severe asthma and non-atopic healthy volunteers (HVs; N = 82; GSK ID: 214099/NCT05602025) were measured. Spearman’s rank correlation coefficient and associated p-values were calculated for patients with severe asthma only. Results In patients with severe asthma from the pooled SWIFT-1/-2 trials, BEC was positively correlated with IL-4 (n = 479; r = 0.38, p 0.0001), IL-5 (n = 503; r = 0.68, p 0.0001), and IL-13 (n = 245; r = 0.51, p 0.0001). Baseline serum IL-4, IL-5, and IL-13 levels were significantly higher in patients with severe asthma compared with the HVs population (all p 0.0001; severe asthma vs HVs, median min, max fg/ml: IL-4, 15.9 3.4, 107.3, n = 479 vs 9.6 2.1, 71.0, n = 81; IL-5, 1107.0 124.8, 17,106.7, n = 503 vs 454.0 114.8, 9926.6, n = 81; IL-13, 44.2 8.1, 431.2, n = 245 vs 16.0 7.6, 72.6, n = 45). Conclusions This study shows that at baseline, BEC was positively and significantly correlated with serum IL-4, IL-5, and IL-13 levels, supportive of the clinical value of BEC as a T2 biomarker. In addition, comparisons with a non-atopic HV cohort confirmed that serum IL-4, IL-5, and IL-13 levels were elevated at baseline in the SWIFT-1/-2 population. Together these findings highlight that the SWIFT -1/-2 population had elevated baseline BEC and serum IL-4, IL-5, and IL-13 levels demonstrating that BEC can be used as a biomarker to select a T2 high population. This abstract is funded by: GSK (HVT 214099; NCT05602025; SWIFT-1/2 206713/213744; NCT04719832/NCT04718103)
Jackson et al. (Fri,) studied this question.