A four-year journey towards clinical remission and background therapies optimization with benralizumab: A retrospective analysis

Background Clinical remission is increasingly recognized as a primary treatment goal in severe asthma, particularly severe eosinophilic asthma (SEA), where comorbidities such as chronic rhinosinusitis with nasal polyps (CRSwNP) contribute to persistent inflammation and treatment burden. Benralizumab, an anti–IL-5Rα monoclonal antibody, has shown efficacy in achieving sustained control in SEA, but long-term real-world data beyond 36 months remain limited. Objective To evaluate the long-term (48-month) effectiveness of benralizumab in SEA patients, focusing on clinical remission, airway function, and reduction of background therapy, including oral corticosteroids (OCS) and inhaled corticosteroids (ICS). Methods In this retrospective, multicenter study across 9 Italian centers, 128 adult SEA patients (mean age 57.1 years, 57% female; 59.4% with CRSwNP) were treated with subcutaneous benralizumab for up to 48 months. Clinical remission was assessed using SANI criteria: partial (pCR, meeting ≥2 of 3 criteria without OCS) and complete (cCR, all criteria fulfilled without OCS). Outcomes included annualized exacerbation rate (AER), pulmonary function (FEV 1 , FEV 1 /FVC, FEF25-75%), airway inflammation (FeNO, blood eosinophils), patient-reported outcomes (ACT, ACQ-6, AQLQ), and background therapy use. Mixed-effects regression models evaluated longitudinal changes. Results Benralizumab induced rapid and sustained improvements. AER decreased from 3.62 to 0.33 at 48 months; blood eosinophils were nearly undetectable throughout. FEV 1 increased from 2.04 L to 2.49 L, with proportional gains in FEV 1 /FVC and FEF25-75%. ACT and ACQ-6 scores improved significantly (p < 0.001), and sinonasal symptoms in CRSwNP patients declined (VAS 4.70 → 2.31). OCS discontinuation was achieved in 88.5% of patients at 48 months, with mean ICS dose reduced by 35%. Overall, clinical remission was observed in 87.9% of patients, with cCR in 63.8%. Improvements were consistent regardless of ICS dose reduction. Conclusions Long-term benralizumab treatment in SEA patients leads to rapid, sustained clinical remission, improved large and small airway function, and significant reduction of background therapy, including OCS and ICS. These results support the role of benralizumab as a disease-modifying therapy and highlight the feasibility of remission-based management in real-world practice.