Treatment of Eosinophilic Granulomatosis With Polyangiitis (EGPA): Do We Need Immunosuppressives?

Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis, distinguished by a complex interplay between type 2 (T2) eosinophilic and non-T2 inflammatory pathways. Systemic glucocorticosteroids remain the mainstay of both induction and maintenance therapy, achieving remission in patients without poor prognostic factors, yet long-term dependence and toxicity remain pervasive challenges. Conventional immunosuppressive agents such as cyclophosphamide (CYC), azathioprine, and methotrexate have been widely used, and rituximab has shown similar remission rates to CYC for induction therapy. However, robust randomized controlled trial evidence supporting their efficacy in EGPA is limited. Biologic therapies targeting eosinophils through IL-5 or IL-5R blockade, notably mepolizumab and benralizumab, have markedly reduced relapse rates, steroid exposure, and improved remission rates in relapsing or refractory disease, with excellent tolerability. Their role in induction is yet to be assessed, alongside novel approaches targeting thymic stromal lymphopoietin and other non-T2 immune pathways. Future priorities include clarifying the contribution of vasculitic versus nonvasculitic mechanisms, the significance of ANCA status, and the immunobiology of relapse. Despite therapeutic inertia in the absence of definitive trials, the collective drive of clinicians and researchers promises to transform and advance management of EGPA in the years ahead.