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Antonio Leon Lloreda, Belen Muñoz-Sánchez, David Echavarria Kashmiri, Maria Luisa Polonio Gonzalez, Maria Victoria Maestre Sanchez, Marta Ferrrer Galvan, Auxiliadora Romero Falcon, Juan Francisco Medina Gallardo, Francisco Javier Alvarez-Gutierrez High-Complexity Asthma Unit. Medical–Surgical Unit of Respiratory Diseases, Virgen Del Rocío University Hospital, Seville, SpainCorrespondence: Antonio Leon Lloreda, High-Complexity Asthma Unit. Medical–Surgical Unit of Respiratory Diseases. Virgen del Rocío University Hospital, Avenue Manuel Siurot, S/N, Seville, 41013, Spain, Email antonio.leon.lloreda.sspa@juntadeandalucia.esAbstract: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic disorder frequently presenting with severe asthma. Mepolizumab, an interleukin-5 inhibitor, is approved for both severe asthma and relapsing or corticosteroid-dependent EGPA, yet treatment response has traditionally been evaluated using systemic-focused scores, such as BVAS, which may underestimate asthma-specific improvements. We conducted a retrospective study of 142 patients with severe uncontrolled asthma (SUA), including 14 with EGPA, all treated with mepolizumab 100 mg every four weeks. Biologic response was assessed using asthma-focused tools, the EXACTO scale and SEPAR-REMAS criteria, which consider exacerbations, asthma control, lung function, and oral corticosteroid (OCS) use. At baseline, EGPA patients exhibited higher prevalence of nasal polyposis and OCS dependence. After one year of treatment, patients with EGPA showed numerically higher rates of good or complete response and clinical remission compared with patients with severe asthma; however, these differences did not reach statistical significance (70% vs 55.7% and 30% vs 18.5%, respectively; p = 0.03). Regarding oral corticosteroid (OCS) use, a higher proportion of EGPA patients remained on OCS after one year (p < 0.001), and the relative reduction in the number of OCS users from baseline was smaller than in the severe asthma group but without statistically significant (p = 0.55). Mean daily OCS dose increased in EGPA (9.8 to 15.3 mg) but decreased in non-EGPA patients (18.4 to 10.3 mg). These findings suggest that patients with SUA and EGPA can achieve asthma-specific improvements with 100 mg mepolizumab, highlighting the value of asthma-focused assessment tools and the need for larger multicenter studies to optimize treatment strategies.Keywords: asthma control, type 2 inflammation, vasculitis spectrum, biologic therapy, precision medicine