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<p>Antineutrophil cytoplasmic antibody&#xa0;(ANCA)-associated vasculitis (AAV) consists of a group of small-vessel vasculitides that often present with organ-threatening or life-threatening manifestations. Current immunosuppressive treatments have improved survival and rates of remission, but are not curative, have frequent toxicities, and do not effectively prevent relapse. Clinical trials have established the role of rituximab, an anti-CD20 B cell-depleting monoclonal antibody, in both the remission-induction and maintenance phases of the disease and demonstrated that glucocorticoid doses can be substantially reduced from historical dosing levels without affecting treatment efficacy. Therapies that have the potential to be more effective and safer have become available or are under investigation. Avacopan, an oral C5a receptor antagonist, was approved as an adjunctive treatment for AAV and use of this drug in combination with rituximab or cyclophosphamide and markedly reduced glucocorticoid dosing demonstrated superior efficacy and potentially greater kidney recovery than prior standard of care. Other agents under study for treatment of AAV include next-generation anti-CD20 monoclonal antibodies, anti-CD19 chimeric antigen receptor T cells, novel complement inhibitors and agents that can target fibrosis. Alongside traditional randomized controlled trials with clinical endpoints, experimental medicine studies are focusing on mechanistic endpoints and disease biomarkers. This Review discusses current treatments and the advances in the management of AAV.</p>

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Advances in the treatment of ANCA-associated vasculitis

  • 期刊论文

  • 发表日期：

    2025年6月5日

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  • Giorgio Trivioli,
  • Marta Casal Moura,
  • Andreas Kronbichler,
  • Rona M. Smith,
  • Benjamin Terrier,
  • Stephen McAdoo,
  • Rachel B. Jones,
  • Peter A. Merkel,
  • David R. W. Jayne

摘要

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) consists of a group of small-vessel vasculitides that often present with organ-threatening or life-threatening manifestations. Current immunosuppressive treatments have improved survival and rates of remission, but are not curative, have frequent toxicities, and do not effectively prevent relapse. Clinical trials have established the role of rituximab, an anti-CD20 B cell-depleting monoclonal antibody, in both the remission-induction and maintenance phases of the disease and demonstrated that glucocorticoid doses can be substantially reduced from historical dosing levels without affecting treatment efficacy. Therapies that have the potential to be more effective and safer have become available or are under investigation. Avacopan, an oral C5a receptor antagonist, was approved as an adjunctive treatment for AAV and use of this drug in combination with rituximab or cyclophosphamide and markedly reduced glucocorticoid dosing demonstrated superior efficacy and potentially greater kidney recovery than prior standard of care. Other agents under study for treatment of AAV include next-generation anti-CD20 monoclonal antibodies, anti-CD19 chimeric antigen receptor T cells, novel complement inhibitors and agents that can target fibrosis. Alongside traditional randomized controlled trials with clinical endpoints, experimental medicine studies are focusing on mechanistic endpoints and disease biomarkers. This Review discusses current treatments and the advances in the management of AAV.