D1.105 - Real-Life Evidence of Type 2 Immunomodulation with Benralizumab: From Steroid-Dependent to Controlled Asthma

Type 2 (T2) inflammation underlies multiple atopic diseases and is orchestrated by T helper 2 cells, group 2 innate lymphoid cells, eosinophils, basophils and IgE. A cytokine environment rich in interleukin (IL)-5 is essential for eosinophil maturation and survival, making the IL-5/IL-5 receptor α (IL-5Rα) axis a central therapeutic target in severe asthma. Benralizumab, a humanized monoclonal antibody anti-IL-5Rα, not only blocks IL-5 signaling but also induces near-complete depletion of eosinophils/basophils through enhanced antibody-dependent cell-mediated cytotoxicity by natural killer cells (NK). Additional mechanisms include antibody dependent cellular phagocytosis by macrophages and amplification of eosinophil apoptosis via tumor necrosis factor (TNF)/TNF receptor 1 and NK-derived interferon-γ.

We present a 28-year-old female with severe asthma and other atopic comorbidities - chronic rhinosinusitis without polyposis, atopic dermatitis and suspected ibuprofen hypersensitivity.

Despite treatment with high-dose inhaled corticosteroids (CS)/long-acting beta adrenergic bronchodilators, inhaled tiotropium, montelukast and oral CS (prednisolone 0,15mg/kg/day), patient’s respiratory symptoms remained uncontrolled, despite optimization of inhaler technique and comorbidities. Immunological profile revealed a T2-high endotype: eosinophils 700/uL, fractional exhaled nitric oxide (FeNO) 91 ppb, total IgE 1324 kU/L and sensitization to dust mites/cat dander. Spirometry confirmed airway obstruction with reversibility: baseline FEV1 2.05L (68%), FEV1 post-bronchodilation 2.56L (85%).Benralizumab was then initiated and, over the course of 18 months, sustained clinical control was observed, allowing CS discontinuation. Moreover, the lung function and biomarkers mirrored clinical outcomes: FEV1 2.74L (91%), eosinophils 140/μL, FeNO 39 ppb and total IgE 671 kU/L. Concomitant atopic conditions also shown clinical improvements.

This case illustrates the immunological cascade triggered by IL-5Rα blockade: rapid eosinophil depletion, reduction of T2 airway inflammation and indirect modulation of IgE responses. Clinical benefits extended to concomitant atopic conditions, highlighting the systemic interconnectedness of T2 inflammation. Such real-world observations provide translational insight into how benralizumab reshapes immune networks, supporting its role as a paradigm of precision immunomodulation in severe eosinophilic asthma.