Mepolizumab for the treatment of eosinophilic granulomatosis withpolyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but potentially life-threatening antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis which affects, to varying degrees, the lungs, paranasal sinuses, heart, kidneys, skin and peripheral nervous system. It is strongly associated with asthma. Peripheral eosinophilia is a defining feature of EGPA and eosinophilic inflammation is often observed in biopsies of affected tissues. Acute and chronic management focuses on the control of inflammation with systemic corticosteroids and other immunosuppressants, all of which carry a significant burden of adverse effects. The development of monoclonal antibody therapies against interleukin-5 (IL-5), the major driver of eosinophilic inflammation, has therefore garnered significant interest among clinicians treating EGPA, who are hopeful that the targeted antieosinophilic effects of such drugs observed in large-scale asthma studies may be replicated in EGPA cohorts. In this review we discuss the features of EGPA, including the current understanding of the eosinophil's role in its pathogenesis. We also review the evidence to date regarding the efficacy of mepolizumab (an anti-IL-5 monoclonal antibody) in severe eosinophilic asthma and the smaller evidence base regarding its efficacy in EGPA, an indication for which it recently received U.S. Food and Drug Administration approval. The possible limitations of mepolizumab in EGPA management are also considered and suggestions put forward regarding the issues that further studies should seek to explore.