Switching from mepolizumab to benralizumab in eosinophilic granulomatosis with polyangiitis (EGPA).

Abstract

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitis characterized by eosinophilic asthma and ENT involvement. Both mepolizumab and benralizumab have demonstrated efficacy in EGPA and are now considered front-line options. In patients who do not respond to mepolizumab, benralizumab may be a valuable alternative owing to its enhanced depletion of eosinophils. We assessed the efficacy for and safety of switching from mepolizumab to benralizumab in EGPA.

Research question: Is benralizumab effective and safe in EGPA patients after mepolizumab failure, given its enhanced depletion of eosinophil?

Study design and methods: We conducted a retrospective European multicenter study including 68 adult EGPA patients who received benralizumab after mepolizumab failure. Complete (CR) and partial (PR) response were defined as BVAS=0, with prednisone ≤4 mg/day and > 4 mg/day, respectively.

Results: Median benralizumab follow-up period was 28 [20-39] months. CR and PR were achieved in 32% and 25% of patients, and maintained at last follow-up in 19% and 16%. Median time to CR was 6 [4-12] months. Forced expiratory volume in one second improved from 73% to 79%, and 38% of patients discontinued glucocorticoids. Vasculitis flares occurred in six patients. Primary mepolizumab failure was associated with lower CR rates (OR 0.19, 95% CI 0.06-0.60). Benralizumab was discontinued in 18% due to persistent respiratory symptoms. Adverse events occurred in five patients, including two severe SARS-CoV-2 infections.

Interpretation: In EGPA patients with persistent respiratory manifestations after mepolizumab failure, switching to benralizumab could represent a valuable option, improving lung function and reducing glucocorticoid use. Further prospective studies are needed to optimize sequencing and patient selection.