ANCA-Associated Vasculitis: State of the Art and Perspectives

Anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitides are characterized by necrotizing inflammation of small blood vessels and primarily affect the kidneys, the lungs, and the upper respiratory tract. These conditions mainly include granulomatosis with polyangiitis and microscopic polyangiitis. Diagnosis relies on serological detection of ANCA directed against myeloperoxidase or proteinase-3, and on biopsy of an affected organ, most commonly the kidney. Management is provided by specialized centers with expertise in ANCA-associated vasculitides. Induction therapy for ANCA-associated vasculitis with kidney involvement or life-threatening manifestations consists of a combination of glucocorticoids and either rituximab or cyclophosphamide. Rituximab is preferred for relapsing cases. A rapid tapering of glucocorticoids, following the PEXIVAS trial regimen, is currently recommended to significantly reduce the risk of severe infections without compromising efficacy. For remission maintenance, fixed and repeated doses of rituximab administered over 18-48 months are preferred over azathioprine. The recent identification of the role of the complement system in the pathogenesis of ANCA-associated vasculitides has led to the development of avacopan, an oral C5a receptor antagonist. Administering avacopan alongside rituximab or cyclophosphamide for one year has demonstrated superior efficacy in achieving remission and kidney recovery, with lower toxicity compared to glucocorticoids, thus representing a promising therapeutic alternative. Keywords ANCA vasculitis, glomerulonephritis, renal failure, rare diseases, autoimmunity