Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study

Abstract

Objective: Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real-life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort.

Methods: We included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015-2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations.

Results: Two hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty-five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty-two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty-four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44).

Conclusion: Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial.

Figure 1

Complete and partial response rates in patients with eosinophilic granulomatosis with polyangiitis who received stable treatment with mepolizumab 100 mg every 4 weeks (A) and 300 mg every 4 weeks (B). Complete response was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and daily prednisone dose ≤4 mg/day. Partial response was defined as no disease activity (BVAS = 0) and daily prednisone dose >4 mg/day. No response was defined as active disease (BVAS >0).

Figure 2

A and B, Variation in disease activity using the Birmingham Vasculitis Activity Score (BVAS) (A) and daily dose of prednisone equivalents (B) among patients with eosinophilic granulomatosis with polyangiitis receiving mepolizumab 100 mg every 4 weeks and those receiving mepolizumab 300 mg every 4 weeks. C and D, Respiratory outcomes in patients during mepolizumab treatment. Kaplan–Meier curves show the occurrence of asthma exacerbations (C) and ear, nose, and throat (ENT) exacerbations (D). E and F, Variation in the forced expiratory volume in 1 second (FEV₁) (E) and eosinophil count (F). Values in A, B, E, and F are the median and interquartile range.* = P < 0.05; ** = P < 0.01, versus baseline.