PO:35:218 | Switching the dose of mepolizumab in patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA): a European retrospective multicentre real-world study

Edoardo Biancalana¹, Irene Mattioli¹, Emanuele Chiara², Danilo Malandrino¹, Maria Canfora¹, Palmerini Miki¹, Maria Paola Lisi¹, Michela Gasparotto³, Paola Tomietto³, Maria Letizia Urban¹, Giacomo Bagni¹, Elena Silvestri¹, Alessandra Bettiol³, Augusto Vaglio³, Giacomo Emmi² | ¹Department of Experimental and Clinical Medicine, University of Florence Firenze, Italy; ²Department of Medical, Surgery and Health Sciences, University of Trieste Trieste, Italy; ³Clinical Medicine and Rheumatology Unit, Cattinara University Hospital, Trieste, Trieste, Italy; ⁴Department of Biomedical, Experimental and Clinical Sciences Mario Serio, University of Florence Firenze, Italy

Background and Aims. Mepolizumab, a monoclonal antibody targeting IL-5, is approved at 300 mg every four weeks for treating Eosinophilic Granulomatosis with Polyangiitis (EGPA) based on the MIRRA trial. However, both 100 mg and 300 mg regimens are used in clinical practice, with limited data on their comparative effectiveness. This study aims to evaluate outcomes in patients with EGPA who switched mepolizumab dosing from 100 mg to 300 mg or vice versa. Materials and

Methods. We included patients with EGPA, classified according to ACR and/or MIRRA trial criteria, treated with mepolizumab and followed at 50 European referral centres. Patients required at least three months of follow-up and a documented dose switch. Reasons for switching, clinical outcomes, and oral corticosteroid (OCS) use after the switch were assessed. Complete response (CR) was defined as BVAS = 0 with prednisone < 4 mg/day; partial response (PR) as BVAS = 0 with prednisone > 4 mg/day.

Results. The final cohort included 145 patients with EGPA, of whom 138 (95%) switched mepolizumab dosage from 100 mg to 300 mg every four weeks, while 7 patients (5%) switched from 300 mg to 100 mg (Table 1). The main reasons for escalation were suboptimal disease control (32%), worsening asthma (28%), ENT symptom deterioration (16%), and facilitating OCS tapering (22%). De-escalation was mainly due to remission (43%), planned strategy (29%), or cost concerns (29%). Among those escalating to 300 mg, 62 (45%) achieved CR, 24 (17%) PR, and 34 (25%) remained stable. Clinical improvement was observed after a median of 4.3 months (IQR 3–6). Only 5% worsened. In the de-escalation group, 3 patients (43%) reached CR, 3 remained stable, and 1 worsened due to an infectious complication. Median time to response was 4.6 months (IQR 3–6). OCS dose decreased in both groups: from 9 to 4 mg/day after escalation, and from 10 to 5 mg/day after de-escalation. BVAS scores also improved in both subgroups (Table 2).

Conclusions. In real-world clinical practice , switching mepolizumab dose from 100 to 300 mg every four weeks enhances disease control and remission rates in patients with EGPA who respond inadequately to 100 mg. Although based on a limited cohort, dose de-escalation from 300 to 100 mg does not seem to compromise clinical control and may be considered as a strategy following sustained remission.