Step-down treatment with mepolizumab for eosinophilic granulomatosis with polyangiitis: a real-life single-centre study

Objectives: To evaluate the efficacy and safety of a step-down treatment approach using mepolizumab for eosinophilic granulomatosis with polyangiitis (EGPA) in a real-life single-centre cohort. The study aimed to assess outcomes following a transition from high-dose (300 mg/4 weeks) to low-dose (100 mg/4 weeks) mepolizumab after achieving remission. Methods: This retrospective study included EGPA patients treated with mepolizumab between April 2014 and December 2024. Patients receiving step-down therapy were in remission, defined by a Birmingham Vasculitis Activity Score (BVAS) of 0, Asthma Control Test (ACT) >20 and steroid-free for at least one year. Disease activity, eosinophil counts and systemic glucocorticoids (GC) use were tracked in medical charts. Results: Among 45 patients initially treated with 300 mg/4 weeks, 12 (27%) switched to 100 mg/4 weeks after a median of 26.5 months. Over a median follow-up of 27.5 months post-step-down, 50% maintained complete remission without GC therapy. In 50% of patients sinonasal symptoms recurred and were treated with either increased mepolizumab dose or optimization of local therapy. No asthma or vasculitis exacerbations occurred. Conclusion: Our preliminary data show that step-down therapy with mepolizumab to 100 mg/4 weeks was effective in maintaining systemic remission and reducing GC use in EGPA patients. However, recurrence of sinonasal symptoms suggests the need for an individualized management. Larger studies are warranted to confirm these findings and optimize dosing strategies for long-term care.