IL-5 Pathway Inhibition in EGPA: Real-World Comparative, Multidimensional Assessment of Mepolizumab and Benralizumab

Background: Monoclonal antibodies targeting IL-5 (mepolizumab) and the IL-5 receptor α (benralizumab) have demonstrated efficacy in eosinophilic granulomatosis with polyangiitis (EGPA). However, despite clinical remission, persistent asthma and ENT symptoms are frequently reported by patients and not fully included by conventional scores such as BVAS. Patient-reported outcome measures (PROMs) may provide a more comprehensive view of disease control. Objectives: to provide an integrated evaluation of EGPA management under biologic therapy through two complementary studies: 1. a real-life 24-month study comparing the long-term effectiveness and safety of benralizumab and mepolizumab (100 mg and 300 mg). 2. an observational longitudinal study assessing the value of patient-reported outcome measures (PROMs) in capturing residual disease burden and their correlation with clinical parameters; Methods The first cohort included patients treated between August 2017 and November 2025 with benralizumab 30 mg, mepolizumab 100 mg, or mepolizumab 300 mg, with a 24-month follow-up. Clinical, laboratory, and functional parameters were assessed at baseline and at 3, 6, 12, and 24 months. Remission was defined as BVAS = 0 and prednisone ≤ 5 mg/day. The second cohort included 40 EGPA patients treated with anti–IL-5/IL-5R or anti–IL-4/13. PROMs (AAV-PRO, SNOT-22, ACT) were collected alongside BVAS, VDI, and prednisone dose. Correlations between PROMs and disease activity indices were analyzed using non-parametric tests. Results In the first study, 66 patients received 81 biologic treatment lines (benralizumab n = 33, mepolizumab 300 mg n = 32, mepolizumab 100 mg n = 16). Remission at 3 months was 81.8%, 46.9%, and 64.3% (p = 0.013), and at 12 months 54.8%, 77.4%, and 41.7% (p = 0.052), respectively. Benralizumab and mepolizumab 300 mg significantly reduced oral corticosteroid use (p < 0.001) and improved lung function. No serious adverse events were observed. In the second study, BVAS significantly decreased to 0 at 12 months (p < 0.001). Despite clinical remission, PROMs revealed a persistent symptom burden, particularly ENT- and asthma-related, with median SNOT-22 and total AAV-PRO scores remaining elevated at 12 months. The PROM domains most strongly correlated with BVAS were Physical Function, Organ-Specific Symptoms in the AAV-PRO, and SNOT-22 (p < 0.001). Conclusion Mepolizumab 300 mg and benralizumab proved effective and safe in long-term EGPA management, offering substantial corticosteroid-sparing and respiratory benefits. PROMs revealed persistent asthma and sinonasal symptom burden even in remission, underscoring their complementary role in assessing disease control. Integrating patient-reported and clinical outcomes may allow a more accurate, individualized approach to EGPA care.