Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis (EGPA): a European multicenter observational study

Objective: Mepolizumab proved efficacious for eosinophilic granulomatosis with polyangiitis (EGPA, former Churg-Strauss) at the dosage of 300mg/4 weeks in the randomized controlled MIRRA trial. Few successful real-life experiences with the dosage approved for severe eosinophilic asthma (100mg/4 weeks) were recently reported. We retrospectively assessed the effectiveness and safety of mepolizumab 100 and 300mg/4 weeks in a large European EGPA cohort. Methods: We included all EGPA patients treated with mepolizumab at the recruiting centres in 2015-2020. Treatment response was evaluated from month 3 through 24 (T3-T24) after mepolizumab starting. Complete response (CR) was defined as no disease activity (Birmingham Vasculitis Activity Score, BVAS=0) and a prednisone dose ≤4mg/day. Respiratory outcomes included asthma and ear-nose-throat (ENT) exacerbations. Results: We included 203 patients, of whom 191 at stable dosage (158 mepolizumab 100mg/4 weeks, 33 300mg/4 weeks). At T3, 25 patients (12.3%) had a CR. CR rates increased to 30.4% and 35.7% at T12 and T24 and were comparable between mepolizumab 100 and 300mg/4 weeks. Mepolizumab led to a significant reduction in BVAS, prednisone dose, eosinophil counts from T3 through T24, with no significant differences between 100 and 300 mg/4weeks. Eighty-two patients (40.4%) experienced asthma exacerbations [57/158 (36%) on 100mg/4 weeks; 17/33 (52%) on 300mg/4 weeks]. Thirty-one (15.3%) experienced ENT exacerbations. Forty-four patients (21.7%) experienced adverse events, most being non-serious (38/44). Conclusion: Mepolizumab both at 100 and 300mg/4 weeks is effective for EGPA. The two dosages should be compared in the setting of a controlled trial.