ANCA vasculitis: what is in the pipeline

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is now recognized as a complex immune-mediated inflammatory disorder rather than a purely pauci-immune small-vessel vasculitis. Advances in understanding ANCA specificity, complement activation, neutrophil extracellular trap formation, genetic susceptibility, and environmental triggers have reshaped concepts of disease classification, prognosis, and therapy. A focused review of these developments is timely because they are directly informing current treatment strategies, disease stratification, and future drug development.

Treatment has shifted from conventional cyclophosphamide and glucocorticoids toward targeted, steroid-sparing approaches. Rituximab is now central to remission induction and maintenance, while avacopan in GPA (granulomatosis with polyangiitis) and MPA (microscopic polyangiitis) and interleukin (IL)-5 blockade in EGPA (eosinophilic granulomatosis with polyangiitis) further reduce glucocorticoid exposure and toxicity. Emerging therapies include next-generation anti-CD20 monoclonal antibodies such as obinutuzumab, CAR-T cell strategies, and other precision immunologic approaches targeting B-cell pathways, including BAFF/APRIL blockade, tyrosine kinase inhibitors (TKIs) and complement-directed therapies designed to more selectively interrupt pathogenic inflammation.

Improved biologic insight is enabling biomarker-driven classification and mechanism-based therapy selection. These advances may reduce treatment-related morbidity, improve durability of remission, and support a more personalized approach to clinical care and translational research in AAV.