RARE DISEASE
Anti-neutrophil cytoplasmic antibody-associated vasculitis
Anti-neutrophil cytoplasmic antibody-associated vasculitis
Anti-neutrophil cytoplasmic antibody-associated vasculitis
Synonyms: AAV, ANCA-associated vasculitis, Antineutrophil cytoplasmic antibody-associated vasculitis
Synonyms: AAV, ANCA-associated vasculitis, Antineutrophil cytoplasmic antibody-associated vasculitis
Synonyms: AAV, ANCA-associated vasculitis, Antineutrophil cytoplasmic antibody-associated vasculitis
Drug discovery
4
drugs
With orphan designations
Overview
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses rare autoimmune disorders (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], eosinophilic granulomatosis with polyangiitis [EGPA]) characterized by necrotizing inflammation of small-to-medium vessels. ANCAs targeting PR3 or MPO trigger neutrophil activation, leading to organ damage (e.g., kidneys, lungs). Diagnosis hinges on clinical features, ANCA testing, and histopathology. Treatment involves glucocorticoids combined with cyclophosphamide or rituximab for induction, followed by maintenance therapy. Emerging biologics (e.g., avacopan) aim to reduce glucocorticoid-related toxicity [1][3][6][13]. Relapses and treatment-related adverse effects contribute to morbidity [1][8][14].
Therapies
Induction: High-dose glucocorticoids + rituximab/cyclophosphamide; plasma exchange for severe renal involvement [1][3][13].
Maintenance: Rituximab/azathioprine/methotrexate for ≥24 months; extended therapy for high-risk relapses [3][8][13].
Emerging therapies: Avacopan (complement C5a inhibitor) for glucocorticoid-sparing effects; mepolizumab for refractory EGPA [5][8][18].
Categories: rare circulatory system diseases, rare respiratory diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood, rare transplant-related disorders
Research Papers
1,827 drug discovery papers about Anti-neutrophil cytoplasmic antibody-associated vasculitis, with 5 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,827 drug discovery papers about Anti-neutrophil cytoplasmic antibody-associated vasculitis, with 5 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-14 | Clinical and electrodiagnostic features of nerve conduction study-classified peripheral neuropathy in symptomatic patients with antineutrophil cytoplasmic antibody-associated vasculitis: a single-centre cohort study.
This study investigated the clinical and electrodiagnostic features of vasculitic peripheral neuropathy (VPN) in symptomatic patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) who underwent nerve conduction studies (NCS) within 3 months after AAV diagnosis. Among 323 patients with AAV, 97 presenting with clinical symptoms suggestive of VPN and with the availability of results of NCS performed within 3 months after AAV diagnosis were included in this study. VPN was classified based on the case definition and guidelines proposed by the Brighton Collaboration Vasculitic Peripheral Neuropathy Working Group in 2017. Of the 97 patients, 12 underwent nerve biopsy. At AAV diagnosis, the median age of the 97 patients was 63.0 years (57% women), consisting of 48 patients with microscopic polyangiitis (MPA), 20 with granulomatosis with polyangiitis (GPA), and 29 with eosinophilic granulomatosis with polyangiitis (EGPA). Among symptomatic AAV patients who underwent early NCS, 55 patients (56.7%) were classified as having electrodiagnostically supported VPN. The most common type of VPN was a mixed type (83.6%), and the most frequently affected nerve was the peroneal nerve (70.9%). The concordance rate between NCS and nerve biopsy findings was 75% based on histological evidence of vasculitis. In this selected cohort of symptomatic AAV patients who underwent NCS within 3 months after diagnosis, more than half were classified as having electrodiagnostically supported VPN. NCS may provide adjunctive objective information for characterizing peripheral nerve involvement in clinically suspected VPN.
2026-08-05 | BAFF and APRIL signaling in the B-cell lineage: implications for the pathogenesis of ANCA-associated vasculitis.
Among the immune mechanisms underlying the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), B-lineage cells play crucial roles by producing ANCA, presenting antigens to T cells, and secreting proinflammatory cytokines. The upregulated signaling pathways of the B-cell activation factor of tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL), which are broadly produced by several types of myeloid cells, contribute to the activation and survival of autoreactive B cells, leading to disease onset and relapse. Furthermore, elevated levels of soluble BAFF and APRIL persist even in patients who achieve clinical remission following conventional induction therapies such as cyclophosphamide and rituximab (RTX), resulting in the cause of relapse. Active AAV is characterized by expansions of specific phenotypes in circulating B-cell lineages, including plasmablasts and plasma cells. Conversely, reductions in transitional, memory, and regulatory B cells are observed. Significant expressions of affinity receptors binding to secreting BAFF/APRIL, including decreased BAFF receptor expression on memory B cells and transitional B cells or increased transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) expression on transitional B cells and plasmablasts/plasma cells, are also observed during acute and remission AAV. Enhanced BAFF and APRIL signaling through these receptors, especially TACI, activates the intracellular nuclear factor-κB pathway in B cells, promoting their proliferation and ANCA production. B-cell depletion therapy using RTX is effective; however, it requires repeated administration to maintain remission, which can occasionally lead to infection. Belimumab, a BAFF-inhibiting monoclonal antibody, alone has shown limited efficacy in preventing relapse of AAV. Targeting BAFF/APRIL signaling pathways and their binding receptors, along with the downstream molecular pathways in targeted B cells, is essential for developing novel therapeutic strategies aimed at achieving complete and sustained AAV remission.
2026-08-05 | Anterior ischaemic optic neuropathy as an initial manifestation of eosinophilic granulomatosis with polyangiitis: The importance of early and appropriate immunosuppressive treatment for visual recovery.
Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody-associated vasculitis, affecting various organs. Although ocular involvement occurred in 6.8-11.1% of patients, anterior ischaemic optic neuropathy (AION) is rare. We present the case of a 57-year-old woman with an 11-year history of asthma who developed sudden, painless visual loss in her left eye. On admission (3 days after symptom onset), visual acuity was counting fingers in the left eye and 20/20 in the right eye. Funduscopy showed left optic disc oedema. Magnetic resonance imaging revealed intravitreal protrusion of the left optic nerve head with restricted diffusion and local contrast enhancement of the left intraorbital and retrobulbar fat. Given also peripheral eosinophilia, myeloperoxidase-antineutrophil cytoplasmic antibody positivity, mononeuritis multiplex, nasal polyps, sinusitis, and pulmonary involvement, EGPA with AION was diagnosed. Intravenous methylprednisolone pulse was urgently administered, followed by mepolizumab 2 weeks later. Although eosinophilic inflammation and imaging findings improved, visual acuity remained unchanged over 1 year. A literature review identified 14 cases of EGPA-associated AION. Including our case, 11 cases with available data (14 eyes) were analysed. Overall, visual recovery was observed in 29%. Among 12 eyes with severe visual impairment before treatment, visual recovery occurred only in those treated earlier or with cyclophosphamide except for one, whereas no recovery occurred in those with delayed treatment or without cyclophosphamide. This case highlights the potential of AION as an initial manifestation of EGPA. Both earlier initiation and adequate intensity of immunosuppressive therapy, particularly including cyclophosphamide when clinically appropriate, may be important for visual recovery in EGPA-associated severe AION.
2026-08-01 | Epidemiology and Clinical Features of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in a Multiethnic Tertiary Care Center Cohort
Objectives At our center, ANCA-associated vasculitis (AAV) is seen with increasing frequency. We have a multiethnic population for whom less information is known about AAV,[1,2] and sought to describe the demographic characteristics, diagnostic settings, and mortality of patients diagnosed with AAV at a single tertiary care center. Methods Records of all patients with AAV were abstracted from 2015-2025 from the electronic medical record at a single tertiary care center. Demographic data, including ethnicity by self-report, diagnostic setting, ANCA subtype (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], and eosinophilic granulomatosis with polyangiitis [eGPA]), and vital status at last follow-up were included. Descriptive statistics were used to characterize the cohort and compare patients from different ethnic backgrounds and ANCA subtypes. Survival was compared using Cox proportional hazard models. Results A total of 334 patients were identified; 192 (58%) were female. Mean age at diagnosis was 53 years ±18; mean disease duration was 10 years ±7. 61% (n=202) of patients were White, 30% (n=101) Indigenous, 8% (n=26) Asian, and 1.5% other (n=5). 49% of patients were diagnosed in a hospital ward, 36% in ambulatory care, 9% in intensive care and unknown in 6%. GPA was diagnosed in 50% (n=167), MPA in 38% (n=128), and EGPA in 11 %. Males were more frequently diagnosed with EGPA (61%, 39% in females; p=0.12) and were older at diagnosis (56±17 years, females 51±19 years; p-0.011). Sixty-two patients (19%) died during the study period. Mean age at death was 61 ±19 years. Indigenous patients were younger at diagnosis (46±18 years; White = 56±18 years; Asian = 55±18 years; p<0.001). Indigenous patients were more often diagnosed with MPA (50%), compared to 34% of white patients and 30% of Asian patients (p = 0.029). More Indigenous patients had died by the end of the follow-up period (28%; White 14%, Asian 19%; p=0.028). Adjusted hazard ratio for mortality was 4.5 (95% CI 2.5-8.3, p<0.001) for Indigenous patients compared to White patients (Figure 1). Figure 1. Adjusted Survival from Disease Onset by Ethnic Group (p <0.001) Conclusion On initial exploratory analysis of a large single center cohort, AAV appears to affect all ethnicities proportionally. We found differences in onset age and AAV subtype between ethnicities, with Indigenous patients diagnosed at a younger age and more often with MPA. Mortality was overall high at 19% during the follow-up period, with adjusted mortality particularly high in Indigenous patients. More studies are needed to determine factors contributing to poor outcomes and differences between ethnic groups. References [1.] Henderson BA. Arthritis Care Res 2025;77:873-80. [2.] Mohammed AJ. Rheumatology 2020;59:iii42-50.
2026-08-01 | Diffuse alveolar hemorrhage in ANCA-associated vasculitis: Current evidence and multimodal treatment approaches.
Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with management largely extrapolated from broader AAV and ARDS literature. We conducted a review of studies published between 2000 and 2025 evaluating treatments and outcomes in AAV-associated DAH, synthesizing evidence across immunosuppressive, plasmapheresis, hemostatic, respiratory and hemodynamic, and infection prevention strategies. Glucocorticoids combined with rituximab or cyclophosphamide induce remission in most patients, although optimal steroid tapering and comparative efficacy in severe, ventilated DAH remain uncertain. Avacopan improves sustained remission and renal recovery in severe AAV and appears to be a feasible steroid-sparing adjunct in early DAH series. Large randomized trials demonstrate no survival benefit of plasma exchange. Local hemostatic therapies may provide rapid bleeding control, but evidence is limited. Respiratory outcomes are driven by hypoxemia severity and need for invasive ventilation or extracorporeal support. Lastly, infection prevention measures are strongly supported.
2026-08-14 | Clinical and electrodiagnostic features of nerve conduction study-classified peripheral neuropathy in symptomatic patients with antineutrophil cytoplasmic antibody-associated vasculitis: a single-centre cohort study.
This study investigated the clinical and electrodiagnostic features of vasculitic peripheral neuropathy (VPN) in symptomatic patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) who underwent nerve conduction studies (NCS) within 3 months after AAV diagnosis. Among 323 patients with AAV, 97 presenting with clinical symptoms suggestive of VPN and with the availability of results of NCS performed within 3 months after AAV diagnosis were included in this study. VPN was classified based on the case definition and guidelines proposed by the Brighton Collaboration Vasculitic Peripheral Neuropathy Working Group in 2017. Of the 97 patients, 12 underwent nerve biopsy. At AAV diagnosis, the median age of the 97 patients was 63.0 years (57% women), consisting of 48 patients with microscopic polyangiitis (MPA), 20 with granulomatosis with polyangiitis (GPA), and 29 with eosinophilic granulomatosis with polyangiitis (EGPA). Among symptomatic AAV patients who underwent early NCS, 55 patients (56.7%) were classified as having electrodiagnostically supported VPN. The most common type of VPN was a mixed type (83.6%), and the most frequently affected nerve was the peroneal nerve (70.9%). The concordance rate between NCS and nerve biopsy findings was 75% based on histological evidence of vasculitis. In this selected cohort of symptomatic AAV patients who underwent NCS within 3 months after diagnosis, more than half were classified as having electrodiagnostically supported VPN. NCS may provide adjunctive objective information for characterizing peripheral nerve involvement in clinically suspected VPN.
2026-08-05 | BAFF and APRIL signaling in the B-cell lineage: implications for the pathogenesis of ANCA-associated vasculitis.
Among the immune mechanisms underlying the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), B-lineage cells play crucial roles by producing ANCA, presenting antigens to T cells, and secreting proinflammatory cytokines. The upregulated signaling pathways of the B-cell activation factor of tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL), which are broadly produced by several types of myeloid cells, contribute to the activation and survival of autoreactive B cells, leading to disease onset and relapse. Furthermore, elevated levels of soluble BAFF and APRIL persist even in patients who achieve clinical remission following conventional induction therapies such as cyclophosphamide and rituximab (RTX), resulting in the cause of relapse. Active AAV is characterized by expansions of specific phenotypes in circulating B-cell lineages, including plasmablasts and plasma cells. Conversely, reductions in transitional, memory, and regulatory B cells are observed. Significant expressions of affinity receptors binding to secreting BAFF/APRIL, including decreased BAFF receptor expression on memory B cells and transitional B cells or increased transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) expression on transitional B cells and plasmablasts/plasma cells, are also observed during acute and remission AAV. Enhanced BAFF and APRIL signaling through these receptors, especially TACI, activates the intracellular nuclear factor-κB pathway in B cells, promoting their proliferation and ANCA production. B-cell depletion therapy using RTX is effective; however, it requires repeated administration to maintain remission, which can occasionally lead to infection. Belimumab, a BAFF-inhibiting monoclonal antibody, alone has shown limited efficacy in preventing relapse of AAV. Targeting BAFF/APRIL signaling pathways and their binding receptors, along with the downstream molecular pathways in targeted B cells, is essential for developing novel therapeutic strategies aimed at achieving complete and sustained AAV remission.
2026-08-05 | Anterior ischaemic optic neuropathy as an initial manifestation of eosinophilic granulomatosis with polyangiitis: The importance of early and appropriate immunosuppressive treatment for visual recovery.
Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody-associated vasculitis, affecting various organs. Although ocular involvement occurred in 6.8-11.1% of patients, anterior ischaemic optic neuropathy (AION) is rare. We present the case of a 57-year-old woman with an 11-year history of asthma who developed sudden, painless visual loss in her left eye. On admission (3 days after symptom onset), visual acuity was counting fingers in the left eye and 20/20 in the right eye. Funduscopy showed left optic disc oedema. Magnetic resonance imaging revealed intravitreal protrusion of the left optic nerve head with restricted diffusion and local contrast enhancement of the left intraorbital and retrobulbar fat. Given also peripheral eosinophilia, myeloperoxidase-antineutrophil cytoplasmic antibody positivity, mononeuritis multiplex, nasal polyps, sinusitis, and pulmonary involvement, EGPA with AION was diagnosed. Intravenous methylprednisolone pulse was urgently administered, followed by mepolizumab 2 weeks later. Although eosinophilic inflammation and imaging findings improved, visual acuity remained unchanged over 1 year. A literature review identified 14 cases of EGPA-associated AION. Including our case, 11 cases with available data (14 eyes) were analysed. Overall, visual recovery was observed in 29%. Among 12 eyes with severe visual impairment before treatment, visual recovery occurred only in those treated earlier or with cyclophosphamide except for one, whereas no recovery occurred in those with delayed treatment or without cyclophosphamide. This case highlights the potential of AION as an initial manifestation of EGPA. Both earlier initiation and adequate intensity of immunosuppressive therapy, particularly including cyclophosphamide when clinically appropriate, may be important for visual recovery in EGPA-associated severe AION.
2026-08-01 | Epidemiology and Clinical Features of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in a Multiethnic Tertiary Care Center Cohort
Objectives At our center, ANCA-associated vasculitis (AAV) is seen with increasing frequency. We have a multiethnic population for whom less information is known about AAV,[1,2] and sought to describe the demographic characteristics, diagnostic settings, and mortality of patients diagnosed with AAV at a single tertiary care center. Methods Records of all patients with AAV were abstracted from 2015-2025 from the electronic medical record at a single tertiary care center. Demographic data, including ethnicity by self-report, diagnostic setting, ANCA subtype (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], and eosinophilic granulomatosis with polyangiitis [eGPA]), and vital status at last follow-up were included. Descriptive statistics were used to characterize the cohort and compare patients from different ethnic backgrounds and ANCA subtypes. Survival was compared using Cox proportional hazard models. Results A total of 334 patients were identified; 192 (58%) were female. Mean age at diagnosis was 53 years ±18; mean disease duration was 10 years ±7. 61% (n=202) of patients were White, 30% (n=101) Indigenous, 8% (n=26) Asian, and 1.5% other (n=5). 49% of patients were diagnosed in a hospital ward, 36% in ambulatory care, 9% in intensive care and unknown in 6%. GPA was diagnosed in 50% (n=167), MPA in 38% (n=128), and EGPA in 11 %. Males were more frequently diagnosed with EGPA (61%, 39% in females; p=0.12) and were older at diagnosis (56±17 years, females 51±19 years; p-0.011). Sixty-two patients (19%) died during the study period. Mean age at death was 61 ±19 years. Indigenous patients were younger at diagnosis (46±18 years; White = 56±18 years; Asian = 55±18 years; p<0.001). Indigenous patients were more often diagnosed with MPA (50%), compared to 34% of white patients and 30% of Asian patients (p = 0.029). More Indigenous patients had died by the end of the follow-up period (28%; White 14%, Asian 19%; p=0.028). Adjusted hazard ratio for mortality was 4.5 (95% CI 2.5-8.3, p<0.001) for Indigenous patients compared to White patients (Figure 1). Figure 1. Adjusted Survival from Disease Onset by Ethnic Group (p <0.001) Conclusion On initial exploratory analysis of a large single center cohort, AAV appears to affect all ethnicities proportionally. We found differences in onset age and AAV subtype between ethnicities, with Indigenous patients diagnosed at a younger age and more often with MPA. Mortality was overall high at 19% during the follow-up period, with adjusted mortality particularly high in Indigenous patients. More studies are needed to determine factors contributing to poor outcomes and differences between ethnic groups. References [1.] Henderson BA. Arthritis Care Res 2025;77:873-80. [2.] Mohammed AJ. Rheumatology 2020;59:iii42-50.
2026-08-01 | Diffuse alveolar hemorrhage in ANCA-associated vasculitis: Current evidence and multimodal treatment approaches.
Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with management largely extrapolated from broader AAV and ARDS literature. We conducted a review of studies published between 2000 and 2025 evaluating treatments and outcomes in AAV-associated DAH, synthesizing evidence across immunosuppressive, plasmapheresis, hemostatic, respiratory and hemodynamic, and infection prevention strategies. Glucocorticoids combined with rituximab or cyclophosphamide induce remission in most patients, although optimal steroid tapering and comparative efficacy in severe, ventilated DAH remain uncertain. Avacopan improves sustained remission and renal recovery in severe AAV and appears to be a feasible steroid-sparing adjunct in early DAH series. Large randomized trials demonstrate no survival benefit of plasma exchange. Local hemostatic therapies may provide rapid bleeding control, but evidence is limited. Respiratory outcomes are driven by hypoxemia severity and need for invasive ventilation or extracorporeal support. Lastly, infection prevention measures are strongly supported.
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Drug Discovery Landscape
4 orphan drug designations for Anti-neutrophil cytoplasmic antibody-associated vasculitis, including 2 approved therapies.
4 orphan drug designations for Anti-neutrophil cytoplasmic antibody-associated vasculitis, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
a humanized IgG4 mAb that binds to hC5aR1 and blocks C5a binding to C5aR1 resulting in inhibition of C5aR1 activation and downstream signaling | antibodies | FDA | 2026-02-19 | — | Otsuka Pharmaceutical Development & Commercialization, Inc |
Gabexate | small molecules | FDA | 2020-09-18 | — | RNR BioMedical Inc. |
avacopan [Tavneos] | small molecules | FDA | 2014-06-02 | 2021-10-07 | ChemoCentryx, Inc. |
rituximab [Rituxan] | antibodies | FDA | 2006-02-14 | 2011-04-19 | Genentech, Inc. |
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