ANCA-associated vasculitis
Looking for the plain-language version? See the patient version of this page.
Safety update: avacopan (Tavneos) should not be started in new patients right now
Health Canada risk communication (7 July 2026, RA-82287): the pivotal ADVOCATE trial supporting avacopan was retracted by the New England Journal of Medicine on 29 June 2026, raising questions about efficacy. Per the retraction notice, the academic authors requested it after an FDA investigation found the primary end-point assessments in 9 of 331 patients were readjudicated after database lock and trial unblinding, undisclosed and inconsistent with proper research conduct. Health Canada advises NOT initiating avacopan in new patients pending its review, and reviewing patients already on it for continued appropriateness (patients should not stop unilaterally). The EULAR 2022 recommendation to consider avacopan rested substantially on ADVOCATE; treat it as superseded by this advisory pending regulatory and guideline updates. Retained below as flagged history, not a current endorsement.[3, 4]
Understanding this condition
What ANCA-associated vasculitis is
AAV comprises GPA (necrotizing granulomatous inflammation with vasculitis; commonly destructive sinonasal disease, pulmonary nodules, pauci-immune glomerulonephritis; usually PR3-ANCA), MPA (vasculitis without granulomatous inflammation; commonly rapidly progressive pauci-immune glomerulonephritis and alveolar haemorrhage; usually MPO-ANCA), and EGPA (eosinophilic tissue infiltration with vasculitis; asthma, eosinophilia, neuropathy). Small- and medium-vessel involvement with multisystem organ disease. Historically high mortality before alkylating agents.[1]
Common symptoms
Constitutional features (fever, fatigue, weight loss, arthralgia) are common. Organ-threatening manifestations defining severe disease include alveolar haemorrhage, glomerulonephritis, CNS vasculitis, mononeuritis multiplex, cardiac involvement, mesenteric ischaemia, and limb or digit ischaemia. Nonsevere features include rhinosinusitis, asthma, mild systemic symptoms, uncomplicated cutaneous disease, and mild inflammatory arthritis.[1]
Who gets it
Rare diseases. Reported European prevalence: GPA about 24 to 157 per million (highest in Sweden and the UK), MPA about 0 to 66 per million (86 per million in Japan), EGPA about 2 to 38 per million. Predominantly adult disease. Figures are from the guideline introduction and are region-specific.[1]
How it is diagnosed
Diagnosis integrates clinical pattern, ANCA serology (PR3-ANCA/c-ANCA typical of GPA, MPO-ANCA/p-ANCA typical of MPA; only about 40 percent of EGPA is ANCA-positive), organ-function testing including urinalysis for glomerulonephritis, imaging, and histology from an involved organ. The 2022 ACR/EULAR classification criteria exist for research; see the classification callout. Serology thresholds and classification scoring to confirm from primary sources.[1]
What to expect over time
Modern induction and maintenance regimens have transformed historically poor survival. Course ranges from monophasic to relapsing; PR3-ANCA positivity and prior relapse are associated with higher relapse risk. Treatment-related morbidity, particularly infection and glucocorticoid toxicity, is a major consideration. All guideline recommendations are conditional, reflecting the limited randomized evidence base.[1]
Living with and treating it
The goals of treatment
Induce remission (Table 1 definition: absence of clinical signs or symptoms attributable to disease, on or off immunosuppression), then maintain it while minimising glucocorticoid exposure. Intensity is matched to severe versus nonsevere disease. See the treat-to-target box for why AAV uses defined disease states rather than a numeric composite target.[1]
Treatment options
Severe/organ-threatening GPA/MPA induction: glucocorticoids plus rituximab (preferred, especially in relapse) or cyclophosphamide, with a GC taper to 5 mg/day by 4 to 5 months. EULAR 2022 also listed avacopan as a glucocorticoid-sparing add-on, but it is not a current induction option: Health Canada advises against initiating it pending review of the retracted ADVOCATE trial (see the safety update above). Nonsevere GPA/MPA induction is the flagged divergence: EULAR 2022 recommends GC plus rituximab (MTX or MMF as alternatives), whereas ACR 2021 recommends methotrexate plus GC over rituximab or cyclophosphamide. Maintenance: rituximab (EULAR strong; ACR conditional), or methotrexate/azathioprine. Severe EGPA: high-dose GC plus cyclophosphamide, or rituximab as an alternative; nonsevere EGPA: GC, with mepolizumab for relapsing or refractory disease. Pneumocystis prophylaxis with trimethoprim-sulfamethoxazole on rituximab, cyclophosphamide, or high-dose GC. Plasma exchange is not routine. All positions verified against ACR/VF 2021 and EULAR 2022 (see the guideline table).[1, 2, 4, 3]
Monitoring and check-ups
Monitor disease activity clinically and by organ-function testing; do not adjust immunosuppression on ANCA titre alone (conditional against). On rituximab maintenance, check for hypogammaglobulinaemia (immunoglobulin supplementation is conditionally recommended if IgG is low with recurrent severe infections). Screen for glucocorticoid toxicity (for example bone mineral density). Agent-specific laboratory monitoring is on the medication guides.[1]
Relapses and how they are treated
Relapse (recurrence of active disease after remission) is managed by re-induction. For severe relapse not on rituximab maintenance, rituximab is conditionally preferred over cyclophosphamide; for severe relapse while on rituximab maintenance, switching to cyclophosphamide is conditionally recommended. PR3-ANCA positivity and prior relapse predict higher relapse risk.[1]
Living well with AAV
Adherence to maintenance therapy is central to relapse prevention. Infection prevention (vaccination, Pneumocystis prophylaxis on rituximab or cyclophosphamide), bone protection during glucocorticoid use, and, in EGPA, optimised asthma and allergy care are key. Care is best delivered with collaboration between rheumatology, nephrology, pulmonology, and otolaryngology, presented alongside nurse-led, NP or PA, and ACPAC-trained extended-role practitioner models, non-exclusively.[1]
Related problems to watch for
Complications include progressive kidney disease (renal transplantation is reasonable in remission with stage 5 CKD), an increased risk of venous thromboembolism, treatment-related infection, and glucocorticoid toxicity. In EGPA, cardiac involvement is a major cause of mortality, and an echocardiogram at diagnosis is conditionally recommended. Chronic sinonasal and airway damage occurs in GPA.[1]
What to expect at your appointment
Initial assessment: multisystem history and examination, ANCA serology, organ-function testing with urinalysis, imaging, and organ biopsy where indicated, with severity staged as severe or nonsevere to guide induction. Multidisciplinary care (rheumatology, nephrology, pulmonology, otolaryngology) is emphasised. Care may be delivered through rheumatologist-led, nurse-led, NP or PA, or ACPAC-trained extended-role practitioner models, presented non-exclusively.[1]
Described in kind only; the 2022 ACR/EULAR classification scoring for GPA, MPA, and EGPA is not in the 2021 management guideline and awaits those primary papers. Same posture as the axSpA and SLE atoms.
AAV is managed to defined disease states rather than a numeric disease-activity composite: remission (absence of signs or symptoms attributable to disease, on or off immunosuppression) followed by relapse-free maintenance. In GPA/MPA, EULAR 2022 adds a specific glucocorticoid taper target: from a starting dose of 50 to 75 mg prednisolone equivalent per day to 5 mg per day by 4 to 5 months, following the PEXIVAS-based reduced-dose schedule (Table 4). ANCA titre alone should not drive therapy. Severe versus nonsevere status sets treatment intensity. (EULAR 2022 also listed avacopan as a glucocorticoid-sparing option, but see the safety update: Health Canada advises against initiating it pending review.)
- Remission (absence of signs or symptoms attributable to disease), on or off immunosuppression
- Glucocorticoid taper to 5 mg prednisolone equivalent/day by 4 to 5 months in GPA/MPA (EULAR 2022, PEXIVAS-based)
- Severe versus nonsevere disease status to set treatment intensity
- Structured clinical assessment, not ANCA or CD19 testing alone, to guide changes
Disease-state definitions verified from ACR/VF 2021 Table 1 and EULAR 2022 Table 1; the glucocorticoid taper target from EULAR 2022 rec 5 and Table 4. No validated numeric disease-activity composite target exists in AAV.
Treatment ladder
- 1
Remission induction: bring the disease under control
Severe/organ-threatening GPA/MPA: glucocorticoids plus rituximab (preferred) or cyclophosphamide; taper GC to 5 mg/day by 4 to 5 months (EULAR 2022, PEXIVAS-based). Nonsevere GPA/MPA (flagged divergence): EULAR 2022 recommends GC plus rituximab (MTX or MMF alternatives); ACR 2021 recommends methotrexate plus GC over rituximab or cyclophosphamide. Severe EGPA: high-dose GC plus cyclophosphamide (rituximab alternative). Nonsevere EGPA: GC, with mepolizumab for relapsing or refractory disease. Avacopan is NOT included as a current induction option here: EULAR 2022 recommended it (rec 6) but Health Canada advises against initiating it pending review of the retracted ADVOCATE trial (see the safety update above).
Verified against ACR/VF 2021 and EULAR 2022. Avacopan is held out of the current ladder per the Health Canada advisory. Mepolizumab has no dedicated general drug guide yet.
- 2
Remission maintenance: keep it quiet
Severe GPA/MPA maintenance: rituximab conditionally preferred over methotrexate or azathioprine; methotrexate or azathioprine over mycophenolate and over leflunomide. EGPA maintenance: methotrexate, azathioprine, or mycophenolate over rituximab and over mepolizumab. Scheduled rituximab re-dosing over ANCA/CD19-guided dosing.
All conditional. Verified from ACR/VF 2021 Tables 2 and 3.
- 3
Relapse: re-induce remission
Severe relapse not on rituximab maintenance: rituximab over cyclophosphamide for re-induction. Severe relapse on rituximab maintenance: switch from rituximab to cyclophosphamide. In EGPA, rituximab is favoured for severe relapse.
All conditional. Verified from ACR/VF 2021 Tables 2 and 3.
- 4
Refractory disease and add-ons
Refractory disease: thorough reassessment of disease status and comorbidities, and switch of induction agent (rituximab to or from cyclophosphamide) over combining; consider adding IVIG; manage in conjunction with a vasculitis centre (EULAR 2022 rec 8). Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole on rituximab, cyclophosphamide, or high-dose glucocorticoids. Plasma exchange is not routine (reserved for serum creatinine above 300 micromol/L due to active glomerulonephritis and for anti-GBM overlap; not routine for alveolar haemorrhage).
Verified against ACR/VF 2021 and EULAR 2022. IVIG has no dedicated general drug guide.
Guideline recommendations
| Topic | Recommendation | Strength | Guideline |
|---|---|---|---|
| Diagnostic ANCA testing | For suspected AAV, test both PR3-ANCA and MPO-ANCA using a high-quality antigen-specific assay as the primary method (EULAR 2022 rec 2).[1] | Strong (EULAR A) | EULAR 2022 (1a/A) |
| Biopsy to support diagnosis | A positive biopsy is strongly supportive; biopsies are recommended to establish a new diagnosis and to evaluate suspected relapse (EULAR 2022 rec 1; ACR/VF 2021).[1] | Conditional (EULAR C) | EULAR 2022 (3b/C); ACR/VF 2021 (biopsy guidance) |
| Severe GPA/MPA remission induction | For organ- or life-threatening GPA/MPA, glucocorticoids plus rituximab or cyclophosphamide; rituximab preferred in relapse (EULAR 2022 rec 3). ACR conditionally prefers rituximab over cyclophosphamide.[1] | Strong (EULAR A); Conditional (ACR) | EULAR 2022 (1a/A); ACR/VF 2021 (conditional) |
| Nonsevere GPA/MPA induction (DIVERGENCE, flagged for Dr. Mahendira) | For non-organ-threatening GPA/MPA induction, EULAR 2022 recommends GC plus rituximab (MTX or MMF as alternatives, rec 4, 1b/B), whereas ACR/VF 2021 recommends methotrexate plus GC over rituximab or cyclophosphamide (conditional). Flagged for adjudication.[1] | Divergent (see cell) | EULAR 2022: glucocorticoids + rituximab, MTX or MMF as alternatives (1b/B). ACR/VF 2021: methotrexate + glucocorticoids over rituximab or cyclophosphamide (conditional). Not resolved here. |
| Glucocorticoid taper target | In GPA/MPA induction, start oral GC at 50 to 75 mg prednisolone equivalent/day and taper to 5 mg/day by 4 to 5 months (EULAR 2022 rec 5, PEXIVAS-based Table 4). ACR concordantly prefers a reduced-dose regimen.[1] | Strong (EULAR A) | EULAR 2022 (1b/A); ACR/VF 2021 (reduced-dose, conditional) |
| Avacopan (superseded by 2026 safety advisory) | EULAR 2022 rec 6 recommended avacopan may be considered with rituximab or cyclophosphamide to reduce glucocorticoid exposure. This is superseded pending review: the pivotal ADVOCATE trial was retracted (NEJM, 29 June 2026) and Health Canada advises not initiating avacopan in new patients and reviewing those already on it (RA-82287, 7 July 2026).[3] | Do not initiate (Health Canada 2026) | EULAR 2022 recommended avacopan with rituximab or cyclophosphamide (rec 6, 1b/B). SUPERSEDED: the ADVOCATE trial was retracted (NEJM, 29 June 2026, doi:10.1056/NEJMe2608684) and Health Canada advises against initiating avacopan in new patients pending review (7 July 2026). |
| Plasma exchange | PLEX may be considered for serum creatinine above 300 micromol/L due to active glomerulonephritis; routine PLEX for alveolar haemorrhage is not recommended (EULAR 2022 rec 7). ACR conditionally recommends against routine addition, favouring consideration in high ESRD-risk patients.[1] | Conditional | EULAR 2022 (1a/B); ACR/VF 2021 (conditional against routine) |
| Severe GPA/MPA remission maintenance | For maintenance after induction with rituximab or cyclophosphamide, rituximab is recommended, with azathioprine or methotrexate as alternatives (EULAR 2022 rec 9). ACR conditionally prefers rituximab over methotrexate or azathioprine.[1] | Strong (EULAR A); Conditional (ACR) | EULAR 2022 (1b/A); ACR/VF 2021 (conditional) |
| Maintenance duration in GPA/MPA | Continue maintenance for 24 to 48 months after induction of remission of new-onset disease; longer for relapsing or high-relapse-risk patients, balanced against preferences and risks (EULAR 2022 rec 10).[1] | Conditional (EULAR B) | EULAR 2022 (1a/B); ACR/VF 2021 (conditional) |
| Do not change therapy on ANCA or CD19 alone | Structured clinical assessment, rather than ANCA and/or CD19+ B cell testing alone, should inform treatment changes (EULAR 2022 rec 15); ACR conditionally recommends against dosing on ANCA titre alone.[1] | Conditional (EULAR B) | EULAR 2022 (1b/B); ACR/VF 2021 (conditional against) |
| Immunoglobulin monitoring on rituximab | Measure serum immunoglobulin concentrations before each course of rituximab to detect secondary immunodeficiency (EULAR 2022 rec 16). ACR recommends immunoglobulin supplementation if IgG is low with recurrent severe infections.[1] | Conditional (EULAR B) | EULAR 2022 (1b/B) |
| Pneumocystis prophylaxis | Trimethoprim-sulfamethoxazole is recommended as prophylaxis against Pneumocystis jirovecii pneumonia and other infections in patients receiving rituximab, cyclophosphamide, and/or high-dose glucocorticoids (EULAR 2022 rec 17; ACR/VF 2021).[1] | Conditional (EULAR B) | EULAR 2022 (3b/B); ACR/VF 2021 (conditional) |
| Severe EGPA remission induction | For organ- or life-threatening EGPA, high-dose glucocorticoids plus cyclophosphamide, with rituximab as an alternative (EULAR 2022 rec 11). ACR conditionally recommends cyclophosphamide or rituximab over mepolizumab.[1] | Conditional (EULAR B) | EULAR 2022 (2b/B); ACR/VF 2021 (conditional) |
| Mepolizumab in relapsing or nonsevere EGPA | Mepolizumab is recommended for relapsing or refractory EGPA without active organ- or life-threatening disease (EULAR 2022 rec 13), and is favoured for maintenance of relapsing nonsevere EGPA (rec 14). ACR recommends mepolizumab as first choice for nonsevere induction and for nonsevere relapse.[1] | Conditional (EULAR B) | EULAR 2022 (1b/B); ACR/VF 2021 (conditional) |
Key points
| Point | Evidence |
|---|---|
| Care is organised as remission induction followed by remission maintenance, with agent choice stratified by severe versus nonsevere disease and by subtype (GPA/MPA versus EGPA).[1] | · |
| For active, severe GPA/MPA, rituximab is conditionally recommended over cyclophosphamide for remission induction, each combined with glucocorticoids; a reduced-dose glucocorticoid regimen is conditionally preferred.[1] | · |
| Minimising glucocorticoid exposure is central. EULAR 2022 sets a taper target of 5 mg prednisolone equivalent per day by 4 to 5 months from a starting dose of 50 to 75 mg/day, following the PEXIVAS-based schedule; ACR 2021 concordantly prefers a reduced-dose regimen.[2, 1] | · |
| In EGPA, mepolizumab is conditionally recommended as first choice with glucocorticoids for active nonsevere disease and for nonsevere relapse; severe EGPA is induced with cyclophosphamide or rituximab over mepolizumab.[1] | · |
| Dosing immunosuppression based on ANCA titre alone is conditionally recommended against; treatment decisions integrate clinical, laboratory, imaging, and biopsy findings.[1] | · |
| Avacopan (oral C5a-receptor inhibitor) was recommended by EULAR 2022 (rec 6) with rituximab or cyclophosphamide to reduce glucocorticoid exposure, but that recommendation rested on the ADVOCATE trial, retracted by NEJM on 29 June 2026; Health Canada advises against initiating it pending review (7 July 2026). Not a current induction option.[2, 3, 4] | · |
Medication guides
Plain-language guides to the medicines used for this condition. Each has a patient and a clinician view.
Key numbers
- Only about 40 percent of EGPA patients are ANCA-positive (guideline introduction), so ANCA-negative status does not exclude EGPA. Contrast with the high ANCA-positivity of GPA and MPA.[1]
References
- Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol. 2021;73(8):1366-1383. doi:10.1002/art.41773 https://doi.org/10.1002/art.41773
- Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024;83:30-47. doi:10.1136/ard-2022-223764 https://doi.org/10.1136/ard-2022-223764
- Rubin EJ. Retraction: Jayne DRW et al. Avacopan for the Treatment of ANCA-Associated Vasculitis, N Engl J Med 2021;384:599-609. N Engl J Med. Published June 29, 2026. doi:10.1056/NEJMe2608684. The academic authors requested retraction after an FDA investigation found the primary end-point assessments in 9 of 331 patients were readjudicated after database lock and trial unblinding, undisclosed and inconsistent with proper research conduct. https://www.nejm.org/doi/10.1056/NEJMe2608684
- Health Canada. TAVNEOS (avacopan) and Health Canada's Review of Data Integrity Concerns. Health professional risk communication, RA-82287. 2026-07-07. States that the pivotal ADVOCATE trial was retracted by the New England Journal of Medicine on 29 June 2026 and advises clinicians not to initiate avacopan in new patients pending review. https://recalls-rappels.canada.ca/en/alert-recall/tavneos-avacopan-and-health-canada-s-review-data-integrity-concerns