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  • Review Article
  • Published:

Advances in the treatment of ANCA-associated vasculitis

Nature Reviews Rheumatology volume 21, pages 396–413 (2025)Cite this article

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Abstract

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.

Key points

  • The main regimen of remission induction in antineutrophil cytoplasmic antibody-associated vasculitis is based on high-dose glucocorticoids combined with rituximab or cyclophosphamide.

  • The initial approach to treatment induces remission of vasculitis in most patients but does not prevent relapse in a substantial number of people and has multiple toxicities.

  • Clinical trial data show that reduced-dose regimens of glucocorticoids are non-inferior to standard-dose regimens and have a lower risk of serious infections; rituximab is superior to azathioprine in maintaining disease remission.

  • B cell-targeting therapies under evaluation for antineutrophil cytoplasmic antibody-associated vasculitis treatment include anti-CD20 monoclonal antibodies with increased B cell depletion capacity compared with rituximab, chimeric antigen receptor T cells and B cell-inhibiting antibodies.

  • Avacopan in combination with rituximab or cyclophosphamide and markedly reduced glucocorticoids has superior efficacy, kidney function recovery and improvement in quality of life to regimens based on standard glucocorticoid dose.

  • Novel targets include pathways involved in antineutrophil cytoplasmic antibody-induced inflammation and fibrosis, which could be combined with immunosuppressive therapies. Strategies to reduce cardiovascular risk and improve response to vaccines are being tested.

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Fig. 1: B cell-targeting and T cell-targeting therapies for AAV.
Fig. 2: Innovative therapies targeting mechanisms of ANCA-induced inflammation.

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Acknowledgements

We thank all our colleagues and members of the European Vasculitis Society and the patients who participated in the studies discussed.

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Authors and Affiliations

  1. Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

    Giorgio Trivioli, Rona M. Smith, Rachel B. Jones & David R. W. Jayne

  2. Department of Medicine, University of Cambridge, Cambridge, UK

    Giorgio Trivioli, Rona M. Smith, Rachel B. Jones & David R. W. Jayne

  3. Mayo Clinic College of Medicine and Science, Rochester, MN, USA

    Marta Casal Moura

  4. Department of Internal Medicine IV, Medical University Innsbruck, Innsbruck, Austria

    Andreas Kronbichler

  5. Hospital Cochin, and Université Paris Cité, Paris, France

    Benjamin Terrier

  6. Imperial College Hospitals, London, UK

    Stephen McAdoo

  7. University of Pennsylvania, Philadelphia, PA, USA

    Peter A. Merkel

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  1. Giorgio Trivioli
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  2. Marta Casal Moura
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  3. Andreas Kronbichler
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Contributions

G.T., M.C.M., A.K. and S.M. researched data for the article. G.T., A.K., R.M.S., R.B.J., P.A.M. and D.J. contributed substantially to the discussion of the content. G.T., M.C.M., A.K., S.P.M. and D.R.W.J. wrote the article. G.T., R.M.S., B.T., S.M., R.B.J., P.A.M. and D.R.W.J. reviewed and/or edited the manuscript before submission.

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Correspondence to Giorgio Trivioli or David R. W. Jayne.

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A.K. has received grant support from CSL Vifor and Otsuka and consultancy and speaking fees from Amgen, AstraZeneca, Boehringer Ingelheim, CSL Vifor, Delta4, GlaxoSmithKline, Miltenyi Biotec, Novartis, Novo Nordisk, Otsuka, Roche, Sobi and Walden Biosciences. B.T. has received consulting fees from AstraZeneca, GlaxoSmithKline, CSL Vifor, Novartis, LFB, Boehringer Ingelheim. R.M.S. has received research grants from GlaxoSmithKline and Union Therapeutics and speaking fees from Vifor. R.B.J. has received research funding from GSK, CSL Vifor, advisory board fees from CSL Vifor and GSK and honoraria from Roche. P.A.M. has received funds for the following activities in the past 2 years: consulting for AbbVie, Alpine, Amgen, ArGenx, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, CSL Behring, GlaxoSmithKline, iCell, Interius, Kinevant, Kyverna, Metagenomia, Neutrolis, Novartis, NS Pharma, Q32, Quell, Regeneron, Sanofi, Sparrow, Takeda, Vistera; research support from AbbVie, Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eicos, Electra, GlaxoSmithKline, Neutrolis, Takeda and stock options from Kyverna, Q32, Sparrow; royalties from UpToDate. D.R.W.J. has received research grants from Roche/Genentech and CSL Vifor, and consulting fees from Amgen, Alentis, Astra-Zeneca, Aurinia, BMS, Boehringer, GSK, Novartis, Roche, Takeda and CSL Vifor.

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Supplementary information

Glossary

Alternative complement pathway

This pathway does not require a trigger, such as immune complexes, but is instead constitutively activated through the ‘tick over’ of C3 and regulatory factors, such as factor H, which are required to prevent widespread activation in the absence of pathogenic stimuli.

Anaphylatoxin

A cytokine that mediates the recruitment and activation of innate immune cells.

Chimeric antigen receptor

(CAR). An engineered receptor that contains an antibody fragment that recognizes unprocessed antigen, such as CD19, and transmembrane and intracellular signalling domains of the T cell receptor complex, which provide activation and co-stimulatory signals in response to antigen binding.

Chimeric autoantigen receptor

(CAAR). An engineered receptor that contains a portion of an autoantigen, potentially PR3, which can be recognized by autoreactive cells, and transmembrane and intracellular domains of the T cell receptor complex.

Cytokine release syndrome

A supraphysiologic inflammatory response (which can progress to multiorgan failure) that can occur following treatment with any immune therapy that activates or engages endogenous or infused T cells and/or other immune effector cells.

Granulomatous inflammation

A form of tissue inflammation that is characterized by the presence of granulomas, structures in which palisading macrophages, including multinucleated giant cells and epithelioid cells and lymphocytes aggregate to surround a core of material, such as apoptotic neutrophils, that cannot be eliminated.

Immune effector cell-associated neurotoxicity syndrome

Neurological symptoms (ranging from mild confusion to seizures and cerebral oedema) that can occur after treatment with any immune therapies that activate or engage endogenous or infused T cells and/or other immune effector cells, leading to damage of the blood–brain barrier.

Immune checkpoints

Molecules that provide co-stimulatory or co-inhibitory signals to T cells that can support or inhibit their activation.

Membrane attack complex

A structure that occurs when the components of the terminal complement pathway assemble and form pores in the cell membrane that can lead to cell lysis.

Neutrophil extracellular traps

(NETs). Net-like structures composed of decondensed chromatin and granule proteins, such as MPO and PR3, that are released as a form of programmed cell death by neutrophils.

T cell tubulitis

Inflammation in the tubule-interstitial compartment of the kidney predominantly driven by T cells.

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Trivioli, G., Casal Moura, M., Kronbichler, A. et al. Advances in the treatment of ANCA-associated vasculitis. Nat Rev Rheumatol 21, 396–413 (2025). https://doi.org/10.1038/s41584-025-01266-1

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