Disclosure(s): No financial relationships with ineligible companies to disclose
Background/Purpose: Glucocorticoid (GC)-dependent asthma and ENT exacerbations may persist in more than half of patients with eosinophilic granulomatosis with polyangiitis (EGPA). Mepolizumab and benralizumab, monoclonal antibodies targeting IL-5 and its receptor, respectively, have demonstrated comparable remission rates in patients with relapsing or refractory EGPA. As mepolizumab was the first approved agent for the treatment of EGPA, a switch to benralizumab is often considered in case of failure of mepolizumab. We aimed to describe the use of benralizumab after mepolizumab failure in patients with refractory EGPA. Methods: We conducted a retrospective multicenter European study of patients with EGPA according to ACR/EULAR classification criteria 2022 who received benralizumab after mepolizumab for inadequate disease control. Complete response was defined as no disease activity (BVAS=0) and a prednisone-equivalent dose ≤4 mg/day, and partial response as no disease activity and a prednisone-equivalent dose >4 mg/day. Results: Fifty-nine patients (median age 55 years [IQR 47; 63]) were included. ANCA was positive in 18 (31%) patients at the time of EGPA diagnosis. Mepolizumab was initiated at a median of 4 years [1; 9] after diagnosis, mainly for uncontrolled asthma (100%) and/or ENT manifestations (61%). The majority of patients received a dose of 100 mg/month (76%), while 14 (24%) received a dose of 300 mg/month. Mepolizumab was discontinued due to lack of efficacy or partial efficacy in 27 (46%) and 25 (42%) patients, respectively, while 7 patients (12%) experienced a respiratory relapse after an initial complete response.
Benralizumab was started a median of 15 months [11; 24] after starting mepolizumab at a dose of 30 mg every 8 weeks in all but one patient. The median follow-up for benralizumab was 33 months [23; 43]. Complete response was achieved in 23 patients (39%) and partial response in 14 patients (24%). However, only 11 of the 23 patients maintained a complete response at the last follow-up. GCs were discontinued in 35 patients (59%) but restarted in 11 (31%). Six patients (10%) experienced a relapse of vasculitis during follow-up, a median of 25 months [16; 25] after starting benralizumab.
Primary refractoriness to mepolizumab to mepolizumab (OR 4.46, 95% CI 1.44–13.83) and the presence of ENT manifestations at the time of benralizumab initiation (OR 4.00, 95% CI 1.22–13.13) were associated with lack of response to benralizumab. FEV1 and eosinophil count at the start of benralizumab were not associated with response. Conclusion: After mepolizumab failure, switching to benralizumab provides a complete response and GC withdrawal in one third of patients. However, this efficacy declines over time in half of the patients. These data suggest that targeting a pathway other than IL-5 may be more effective in patients who do not respond to mepolizumab.
