C33-25 Lung Function Decline on Benralizumab Associated With an Il-13 Signature

Abstract Introduction Biologic therapies targeting type 2 inflammatory pathways have transformed the management of severe asthma.1 We report a case of asthma deterioration and severe dermatitis following initiation of benralizumab(anti-interleukin-(IL)-5-receptor-alpha, IL-5Rα), lack of response to dual biologic therapy with benralizumab and dupilumab (anti-IL-4Rα), and complete remission after switching to dupilumab monotherapy. Clinical Summary A 21-year-old woman with atopic dermatitis, allergic rhinitis, elevated immunoglobulin-E (20,000 kU/L) and eosinophilia (peak 1.7 × 109/Liter)was diagnosed with severe T2-high asthma. Despite high-dose budesonide/formoterol and tiotropium, she experienced recurrent exacerbations, fluctuating airflow limitation (45-98% predicted) and persistent symptoms. In November 2023, benralizumab was initiated given eosinophilic phenotype. Within weeks, she developed diffuse eczematous rash, worsening asthma control, elevated fractional-exhaled-nitric-oxide of 36-65 parts-per-billion, FEV1 decline to 59%predicted, and significant mucus plugging on chest computed tomography, despite complete eosinophil depletion. IL-13 is closely associated with high FeNO and mucus plugging.2 Additionally, IL-4 and IL-13 blockade via dupilumab is effective in patients with chronic sinusitis and atopic dermatitis.3,4 Given the clinical findings and biomarkers, symptomatic worsening was thought to be due to an increase in IL-13. Addition of dupilumab as dual biologic treatment in June 2024 failed to achieve meaningful improvement, with persistent symptoms, eczema flares, and reduced lung function. Persistent symptoms were hypothesized to be due to counterregulatory increase in IL-13 due to IL-5 blockade. As such, in March2025, benralizumab was discontinued and dupilumab continued as monotherapy. Within three months, she achieved complete asthma control, normalization of FEV1 (101%predicted), reduction of FeNO to 15 ppb, resolution of eczema and sustained over six months without exacerbations. Conclusion This case highlights a disease process predominantly driven by IL-4/IL-13-mediated inflammation, unresponsive to IL-5/IL-5Rα blockade despite eosinophilia. The association of atopic dermatitis, asthma worsening with benralizumab, elevated FeNO,mucus plugging, lack of response to dual therapy, and rapid remission on Dupilumab monotherapy suggests counterregulatory increase in IL-13 signature with IL-5blockade. Limitation of this case includes lack of sputum biomarkers including cell counts and cytokine analysis. This case highlights the importance of precise phenotyping and biomarker assessment before biologic selection. References: 1. Gyawali B et al. Eur Respir Rev. 2025 Jan 8;34(175):240088. 2. Svenningsen S et al. Chest. 2019 Jun;155(6):1178-1189. 3. Bachert C et al. Lancet. 2019 Nov 2;394(10209):1638-1650. 4. Simpson EL et al. N Engl J Med. 2016 Dec 15;375(24):2335-2348. This abstract is funded by: No third party, it was conducted in the university