PO:35:234 | Sustained Vasculitis Quiescence and CS Reduction with Mepolizumab 100 mg

Francesca Mascia¹, Angelo Fassio², Marco Zurlo¹, Davide Chesini³, Francesco Pollastri², Giovanni Adami², Davide Gatti⁴, Maurizio Rossini⁴, Matteo Maule⁵, Gianentrico Senna¹, Marco Caminati¹ | ¹University of Verona - Allergology and Clinical Immunology Verona, Italy; ²Policlinico G. B. Rossi - Rheumatology Verona, Italy; ³University of Verona - Faculty of Medicine and Surgery Verona, Italy; ⁴University of Verona - Rheumatology Verona, Italy; ⁵Policlinico G. B. Rossi - Allergology and Clinical Immunology Verona, Italy

Introduction. Eosinophilic granulomatosis with polyangiitis (EGPA) is an uncommon systemic necrotizing vasculitis of small- to medium-sized vessels, defined by adult-onset asthma, marked peripheral eosinophilia and multisystem involvement. Standard of care comprises high-dose corticosteroids combined with immunosuppressive agents, a regimen frequently associated with treatment-related toxicity. Mepolizumab, a fully human monoclonal antibody against interleukin-5, has been approved for EGPA at 300 mg administered every four weeks, although many patients maintain sustained vasculitic remission with the asthma prescription of 100 mg every four weeks.

Objective and Methods. In this single-centre observational study at the University Hospital of Verona we aimed to assess the long-term efficacy, safety and CS/IS-sparing impact of mepolizumab 100 mg monthly in EGPA patients whose vasculitis was quiescent but who continued to experience refractory eosinophilic asthma. We enrolled 36 patients meeting ACR criteria for EGPA, with severe steroid-dependent asthma and Birmingham Vasculitis Activity Score (BVAS)–confirmed remission, received mepolizumab 100 mg every four weeks. Clinical data were retrospectively collected at disease onset, at treatment initiation (baseline), and at 6, 12, 18 and 24 months. We recorded BVAS, daily prednisone dose, concomitant IS use, peripheral eosinophil count, ANCA status, FEV1 % predicted, fractional exhaled nitric oxide (FeNO), Asthma Control Test (ACT) scores, asthma exacerbations and hospitalizations. Repeated measures ANOVA evaluated parameter trends over time. A Cox proportional hazards model examined whether baseline BVAS, prednisone dose or ANCA status predicted time to IS discontinuation. Remission at 24 months was defined per MIRRA criteria as BVAS = 0 with prednisone < or = 4 mg/day.

Results and Conclusions. At baseline, no patient met remission criteria, by months 12 and 24, 10 of 36 patients achieved remission, with no significant difference between ANCA-positive and ANCA-negative subgroups. BVAS and eosinophil counts declined significantly (p < 0.001). Median daily prednisone fell from approximately 50 mg at baseline to < or = 4 mg, enabling 75% of patients to discontinue corticosteroids by 24 months. ACT scores improved, FeNO levels declined and FEV1 remained stable. Rates of asthma exacerbation and hospitalization approached zero. Six patients (14%) required dose escalation to 300 mg or switching biologic due to flares. In Cox regression, higher baseline BVAS was associated with a lower likelihood of IS discontinuation (HR 0.87; 95% CI, 0.78–0.97; p = 0.014). Mepolizumab 100 mg monthly led to sustained reductions in vasculitis activity, eosinophil counts and CS/IS requirements, supporting an “asthma-tailored” low-dose strategy for EGPA patients in remission. Future multicenter randomized trials and biomarker studies are necessary to optimize patient selection and dosing strategies for long-term management.