The Expanding Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Armamentarium

The complex pathophysiology of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) is reflected in the heterogeneity of the presenting clinical syndromes caused by these diseases but also provides a variety of conceivable molecular and cellular targets that can be therapeutically manipulated. The last decade has seen an expansion of established and potential therapies for treating AAV, some of which target the dysfunctional autoreactive immune response and others aim to ameliorate the downstream consequences of local vascular inflammation and necrosis. The success and widespread adoption of the anti-CD20 monoclonal antibody, rituximab, as an agent to both induce and maintain remission, has heralded a change in the standard-of-care management of AAV, replacing the "old guard" combination of cyclophosphamide and high-dose corticosteroids established in the 1970s. The development and approval of avacopan, a first-in-class small-molecule antagonist to the main receptor for the complement anaphylatoxin C5a, has the potential to reduce the corticosteroid burden experienced by patients with AAV and may also improve outcomes for those with AAV kidney disease. It marks the culmination of almost 20 years of international collaboration, from understanding the pathological role of complement in basic murine models of AAV through to a phase III clinical trial, and emphasises the importance of following promising translational discoveries through to drug development and clinical deployment. This article summarises how recent progress in our understanding of the basic pathophysiology of AAV has resulted in the development of new and effective treatments and, reciprocally, how studying the impact of these treatments in patients has advanced our understanding of dysfunctional immunobiology in disease.