D1.130 - Immune markers after one year treatment with benralizumab in severe eosinophilic asthma

Benralizumab is a monoclonal antibody directed against the IL-5 receptor leading to rapid and sustained depletion of eosinophils which is used for severe eosinophilic asthma. However, evidence about the effect of this medication on different immune markers is lacking. The aim of this study was to evaluate patterns of local and systemic immune markers after 1 year treatment with benralizumab in severe eosinophilic asthma.

We conducted a retrospective single-centre study at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics. Adult patients with severe asthma (according to GINA) treated with benralizumab for at least a year from 2023 to 2025 were included. Peripheral blood eosinophils, lymphocyte subpopulations, cytokines (IL-4, IL-33, IL-22, IL-5, TNF-α, IFN-γ, IL-10, IL-2, IL-13) and IgE in serum and nasal lavage were evaluated at baseline and after 1 year of treatment.

A total of 19 patients were included in the study (median age 58 years, range 22-65). Peripheral blood eosinophils were rapidly depleted by the first follow-up and remained suppressed during observation. No significant changes were observed in CD3⁺, CD4⁺, CD8⁺, CD19⁺, or CD16⁺/CD56⁺ lymphocyte subpopulations. Th2 cells significantly reduced (3.7 (0.26-8.40) versus 1.23 (0.0-5.45), p = 0.00006), while Th17 cells increased (1.2 (0.13-3.31) versus 2.21 (0.36-10.65), p = 0.029). Th1 and Th22 subsets remained stable. Serum cytokine analysis showed significant reductions in IFN-γ and TNF-α (3.22 (0.0-761.3) versus 0.0 (0.0-21.7), p = 0.028 and 135.2 (35.8-500) versus 77.4 (15.8-500), p = 0.044), whereas serum IgE and other cytokines showed no significant longitudinal changes. In nasal lavage fluid, Th2-associated cytokines IL-4 and IL-13 were significantly reduced (10.37 (1.98-17.86) versus 0.0 (0-3.87), p = 0.002 and 3.93 (0.0-7.0) versus 0.0 (0.0-0.0), p = 0.0116), accompanied by decreased IgE (0.023 (0.0-1.18) versus 0.0 (0-0.582), p = 0.042). IL-33 levels in nasal lavage fluid were also reduced (0.0 (0.0-11.5) versus 0.0 (0.0-0.0), p = 0.0422).

In severe eosinophilic asthma after 1 year treatment with benralizumab levels of IL-4, IL-13, IL-33, and IgE in nasal lavage fluid, as well as IL-4, IL-13, TNF-α, and IFN-γ in peripheral blood significantly reduced, suggesting a broader local and systemic immunomodulatory effect.

The study was sponsored by "AstraZeneca".