⚡ Quick Start — If You Read Nothing Else

The 8 most important things to know right now.

AAV is a rare but serious autoimmune disease that inflames blood vessels. ANCA-associated vasculitis (AAV) causes inflammation of small blood vessels throughout the body, most commonly affecting the kidneys, lungs, sinuses, and nerves. Without treatment, it can cause permanent organ damage.
There are two main types: GPA and MPA. Granulomatosis with polyangiitis (GPA, formerly Wegener’s) typically affects the upper airways, lungs, and kidneys. Microscopic polyangiitis (MPA) primarily affects kidneys and lungs. Both require the same core treatments.
ANCA blood tests are central to diagnosis. Most AAV patients test positive for ANCA antibodies: PR3-ANCA (common in GPA) or MPO-ANCA (common in MPA). ANCA-negative disease exists but is less common.
Rituximab has replaced cyclophosphamide as preferred first-line therapy for most patients. The RAVE trial established rituximab as equally effective and better tolerated than cyclophosphamide for inducing remission, especially in relapsing disease.
Avacopan (Tavneos), approved in 2021, can reduce or eliminate glucocorticoids while improving kidney outcomes. This first-in-class oral complement C5a receptor inhibitor is added to (not a replacement for) rituximab or cyclophosphamide. Important: in 2026 the FDA warned of serious/fatal liver injury and proposed withdrawing it from the market — see the avacopan safety alert below and discuss its current status with your specialist.
Maintenance therapy is essential — AAV relapses frequently. After achieving remission, maintenance therapy with rituximab (preferred) or azathioprine for 2–4 years significantly reduces relapse risk. Stopping maintenance too early is the most common cause of preventable relapse.
Kidney involvement requires urgent specialist care. Rapidly progressive glomerulonephritis (RPGN) can lead to dialysis within days to weeks if untreated. If kidney function is declining rapidly, treatment must begin immediately, sometimes before biopsy results are back.
Get to a vasculitis specialist. AAV is rare enough that many general physicians have limited experience managing it. Care at a center with a dedicated vasculitis program significantly improves outcomes. The Vasculitis Foundation can help locate specialists.

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Understanding ANCA-Associated Vasculitis

ANCA-associated vasculitis (AAV) is a group of rare autoimmune diseases that cause inflammation of small blood vessels throughout the body. The term “ANCA” refers to anti-neutrophil cytoplasmic antibodies — immune system proteins that mistakenly attack the body’s own white blood cells (neutrophils), causing them to damage the walls of small blood vessels.

When small blood vessels become inflamed and damaged, the organs they supply are starved of blood flow and become injured. The kidneys, lungs, sinuses, ears, eyes, nerves, skin, and joints are the most commonly affected organs, but AAV can affect virtually any organ system.

Approximately 40,000 people in the United States are living with AAV
Annual incidence is approximately 20–25 new cases per million people
GPA and MPA occur roughly equally; GPA is more common in Northern Europe and the US, while MPA is more common in Southern Europe and Japan
AAV can occur at any age but most commonly presents between ages 50–70
Slightly more common in men than women for GPA; roughly equal for MPA
EGPA (eosinophilic granulomatosis with polyangiitis, formerly Churg-Strauss) is a related but distinct condition not covered in detail in this guide

Granulomatosis with polyangiitis (GPA): Formerly called Wegener’s granulomatosis. Typically causes granulomatous inflammation in the upper airways (sinuses, nose, ears), lungs, and kidneys. Often associated with PR3-ANCA antibodies. Can cause nasal crusting, bloody nose, saddle-nose deformity, hearing loss, cough, and kidney failure.
Microscopic polyangiitis (MPA): Primarily affects the kidneys and lungs without the granulomatous inflammation seen in GPA. Often associated with MPO-ANCA antibodies. Can cause rapidly progressive kidney failure and, less commonly, diffuse alveolar hemorrhage (bleeding into the lungs).
EGPA (eosinophilic granulomatosis with polyangiitis): A related but distinct condition associated with asthma, eosinophilia, and vasculitis. Has different treatment approaches and is not the primary focus of this guide.

Important: The distinction between GPA and MPA matters somewhat for prognosis and relapse risk, but the core treatment approach (rituximab or cyclophosphamide for induction, rituximab or azathioprine for maintenance) is similar for both.

The most important concept in this guide: AAV is a chronic disease that can be controlled but rarely cured. The goals of treatment are to achieve remission (stop the inflammation), prevent organ damage, minimize treatment side effects, and reduce relapse risk through maintenance therapy. With modern treatment, most patients achieve remission and many live normal lifespans, but lifelong monitoring is essential.

Key Breakthroughs in AAV

The AAV treatment landscape has improved dramatically over the past 15 years. Here are the most important advances:

FDA-APPROVED Avacopan is a first-in-class oral complement C5a receptor inhibitor approved in October 2021. The ADVOCATE trial demonstrated that avacopan, added to rituximab or cyclophosphamide, allowed significant reduction in glucocorticoid (prednisone) exposure while achieving equivalent or better remission rates and significantly better kidney outcomes at 52 weeks. This is a paradigm shift because it addresses one of the biggest problems in AAV treatment: the severe side effects of long-term high-dose prednisone.

FDA-APPROVED The RAVE trial (NCT00104299), published in 2010, demonstrated that rituximab was non-inferior to cyclophosphamide for inducing remission in severe AAV. Rituximab was actually superior in relapsing disease. This fundamentally changed AAV treatment by offering a less toxic alternative to cyclophosphamide, which carried risks of infertility, bladder cancer, and severe infections.

GUIDELINE-SUPPORTED The MAINRITSAN trial showed that rituximab maintenance (500 mg every 6 months) was significantly superior to azathioprine for preventing relapse after remission induction. MAINRITSAN-2 showed that ANCA-guided rituximab dosing was as effective as fixed-schedule dosing. RITAZAREM (NCT01697267) confirmed that rituximab maintenance was superior to azathioprine in patients with relapsing disease. These trials established rituximab as the preferred maintenance agent, especially for patients at high relapse risk (PR3-ANCA positive, relapsing disease).

PRACTICE-CHANGING The PEXIVAS trial (NCT00987389), published in 2020, was the largest randomized trial ever conducted in AAV. It showed that plasma exchange (plasmapheresis) did NOT reduce death or end-stage kidney disease at 12 months compared to standard immunosuppressive therapy alone. This reversed decades of practice where plasma exchange was routinely used in severe renal AAV. PEXIVAS also showed that a reduced-dose glucocorticoid regimen was non-inferior to the standard higher-dose regimen.

PRACTICE-CHANGING Both the PEXIVAS and LoVAS trials have supported the use of reduced-dose glucocorticoid protocols, with shorter tapers to lower cumulative steroid exposure. The ADVOCATE trial further demonstrated that avacopan can replace most prednisone use. This is clinically important because long-term glucocorticoid side effects (diabetes, osteoporosis, infections, cataracts, weight gain, mood changes) are a major source of morbidity in AAV — sometimes causing more harm than the disease itself.

Diagnosis: The Tests You Need

AAV diagnosis is based on a combination of clinical symptoms, ANCA blood testing, and, in most cases, tissue biopsy. No single test is sufficient on its own — the diagnosis requires putting together the clinical picture.

The ANCA test is the single most important blood test in diagnosing AAV. There are two main ANCA targets:

PR3-ANCA (proteinase 3): Positive in approximately 75–80% of GPA patients and some MPA patients. Also called c-ANCA when detected by immunofluorescence.
MPO-ANCA (myeloperoxidase): Positive in approximately 60–70% of MPA patients and some GPA patients. Also called p-ANCA by immunofluorescence.

Important limitations: About 10–15% of AAV patients are ANCA-negative, particularly in localized GPA (disease limited to the sinuses/airways without kidney involvement). A negative ANCA test does NOT rule out AAV if the clinical picture is suggestive. Modern testing uses specific antigen immunoassays (ELISA or chemiluminescence for PR3 and MPO) rather than the older, less specific immunofluorescence method alone.

Kidney biopsy is the gold standard for confirming kidney involvement in AAV and is strongly recommended whenever kidney function is impaired and AAV is suspected. The biopsy shows:

Pauci-immune crescentic glomerulonephritis: The hallmark finding in AAV kidney disease. “Pauci-immune” means little or no antibody deposition on immunofluorescence (unlike lupus nephritis).
Crescents: Crescent-shaped cellular proliferations in the glomeruli, indicating active inflammation.
Sclerosis: Scarring of glomeruli, indicating chronic damage that may not be reversible.

The ratio of active (crescentic) to chronic (sclerotic) lesions on biopsy helps predict kidney outcomes and guides treatment intensity. The Berden classification divides AAV kidney biopsies into focal, crescentic, mixed, and sclerotic categories.

Blood tests: Kidney function (creatinine, eGFR), inflammatory markers (ESR, CRP), complete blood count, urinalysis with microscopy (looking for blood and protein in urine, especially red blood cell casts)
CT scan of the chest: To evaluate for lung involvement (nodules, cavities, ground-glass opacities indicating alveolar hemorrhage)
CT or MRI of sinuses: In GPA, to evaluate for sinus inflammation, destruction, or granulomatous disease
Lung biopsy: Sometimes needed when lung nodules or cavities are present and infection or cancer must be excluded
Nasal/sinus biopsy: Can show granulomatous inflammation characteristic of GPA
Nerve conduction studies: If numbness, tingling, or weakness suggests nerve involvement (mononeuritis multiplex)

Was I tested for both PR3-ANCA and MPO-ANCA using the modern specific assays?
Do I have GPA or MPA, and does the distinction matter for my treatment?
Is a kidney biopsy recommended in my case? What will it tell us?
Which organs are currently affected by my vasculitis?
How much kidney function do I have right now, and is it declining?
Is this a new diagnosis or could I have had this for a while before it was recognized?
Should I see a vasculitis specialist for a second opinion?
What is my BVAS (Birmingham Vasculitis Activity Score) — how active is my disease right now?

ANCA Types — What They Mean for You

The specific type of ANCA antibody you have provides important information about your likely disease course and relapse risk.

ANCA Type	Associated Disease	What This Means
PR3-ANCA	Most commonly GPA; some MPA	Higher relapse risk (up to 50–70% over 5 years without maintenance). Rituximab maintenance is generally preferred. Disease may involve upper airways, lungs, and kidneys. Rituximab may be superior to cyclophosphamide for induction in relapsing PR3-ANCA disease (RAVE trial subgroup).
MPO-ANCA	Most commonly MPA; some GPA	Lower relapse risk than PR3-ANCA but higher risk of chronic kidney damage. Disease tends to be more kidney-predominant. Both rituximab and cyclophosphamide are effective for induction. Azathioprine maintenance may be reasonable for some low-risk MPO-ANCA patients.
ANCA-negative	GPA (especially localized) or MPA	Approximately 10–15% of AAV patients. Diagnosis relies more heavily on biopsy and clinical features. Same treatment approach as ANCA-positive disease. May have a different underlying biology.

Important: Rising ANCA levels during remission may predict relapse, particularly for PR3-ANCA. However, a rising ANCA alone, without clinical symptoms, is generally NOT a reason to change treatment immediately. Discuss with your specialist how they use serial ANCA monitoring in your care. Some centers use rising ANCA to trigger pre-emptive rituximab dosing (MAINRITSAN-2 approach).

Organ Involvement in AAV

AAV can affect many organs. Understanding which organs are involved helps guide treatment urgency and monitoring.

Kidney involvement is the most common serious manifestation. It typically presents as rapidly progressive glomerulonephritis (RPGN) — a rapid decline in kidney function over days to weeks. Symptoms may be subtle early on: blood or protein in the urine (often detected only by testing), rising creatinine, and sometimes edema or high blood pressure.

Why it matters: Kidney damage from AAV can be permanent. The sooner treatment begins, the more kidney function can be preserved. About 20–25% of AAV patients eventually develop end-stage kidney disease requiring dialysis or transplant, but this rate is improving with earlier diagnosis and better treatment.

Lung involvement can range from mild cough to life-threatening diffuse alveolar hemorrhage (DAH) — bleeding into the air sacs of the lungs.

Lung nodules and cavities: Common in GPA. Can mimic cancer or infection. Biopsy may be needed to confirm vasculitis.
Diffuse alveolar hemorrhage: A medical emergency. Presents with cough, hemoptysis (coughing blood), shortness of breath, and dropping hemoglobin. Requires urgent immunosuppression. The combination of DAH and RPGN is called pulmonary-renal syndrome.
Airway stenosis: Narrowing of the trachea or bronchi due to scarring. More common in GPA. May require interventional procedures (dilation, stenting).

Sinusitis: Chronic, often bloody nasal discharge, nasal crusting, and recurrent sinus infections that do not respond to antibiotics
Saddle-nose deformity: Collapse of the nasal bridge due to cartilage destruction
Hearing loss: Conductive (middle ear involvement) or sensorineural (inner ear vasculitis)
Subglottic stenosis: Narrowing below the vocal cords causing hoarseness and breathing difficulty. May require ENT procedures. Can occur independently of systemic disease activity.

Peripheral neuropathy (mononeuritis multiplex): Sudden numbness, pain, or weakness in specific nerve distributions, often affecting feet and hands asymmetrically. Occurs in 20–40% of patients.
Skin: Purpura (small purple spots from bleeding under the skin), ulcers, nodules. Occurs in 30–50% of patients.
Eyes: Scleritis (painful red eye), episcleritis, orbital masses (GPA), retinal vasculitis. Eye involvement can threaten vision and requires ophthalmology evaluation.
Joints: Joint pain (arthralgias) and sometimes arthritis. Common but rarely destructive. Often the earliest symptom.
Constitutional symptoms: Fatigue, weight loss, fevers, and night sweats are common at presentation.

Key question for your specialist: “Which of my organs are currently affected by vasculitis, and which ones are at greatest risk of permanent damage? How will you monitor each organ system?”

Induction (Remission) Therapy

The goal of induction therapy is to rapidly suppress the overactive immune system and stop the vasculitis from damaging organs. Treatment urgency depends on the severity of organ involvement. For active, severe AAV (kidney involvement, lung hemorrhage, nerve damage), treatment must begin urgently.

FDA-APPROVED Rituximab is a monoclonal antibody that depletes B cells (a type of immune cell that produces ANCA antibodies). It was FDA-approved for AAV induction in 2011 based on the RAVE trial (NCT00104299).

Dosing: 375 mg/m² IV weekly for 4 weeks (RAVE protocol) OR 1000 mg IV on days 1 and 15 (rheumatoid arthritis dosing, widely used in practice)
Remission rate: Approximately 64% complete remission at 6 months (similar to cyclophosphamide)
Advantages over cyclophosphamide: No risk of infertility, no increased risk of bladder cancer, generally better tolerated
Particularly preferred for: Relapsing disease (superior to cyclophosphamide in this setting), patients who wish to preserve fertility, patients with prior cyclophosphamide exposure

Given with glucocorticoids: Rituximab is typically given alongside prednisone (starting at approximately 1 mg/kg/day, tapered over 3–6 months). With avacopan, the glucocorticoid dose can be significantly reduced.

GUIDELINE-SUPPORTED Cyclophosphamide was the original standard of care for AAV and remains effective for inducing remission. It may still be preferred in certain situations:

Oral cyclophosphamide: 2 mg/kg/day for 3–6 months, then switch to maintenance
IV pulse cyclophosphamide: 15 mg/kg (max 1.2 g) every 2–3 weeks for 3–6 months. Lower cumulative dose than oral, preferred in Europe.
When cyclophosphamide may be preferred: Very severe kidney involvement with high percentage of crescents on biopsy, situations where rituximab is contraindicated (active hepatitis B), limited access to rituximab

Key risks: Infertility (dose-dependent; discuss fertility preservation before starting), increased lifetime risk of bladder cancer (especially with oral dosing), bone marrow suppression, infections.

Glucocorticoids are a critical component of initial AAV treatment because they act quickly to suppress inflammation while waiting for rituximab or cyclophosphamide to take full effect.

IV pulse methylprednisolone: 500–1000 mg IV daily for 1–3 days for severe presentations (RPGN, DAH)
Oral prednisone: Starting dose typically 1 mg/kg/day (max 60–80 mg), tapered over 3–6 months
Reduced-dose protocols: PEXIVAS demonstrated that a faster prednisone taper (reaching lower doses sooner) was non-inferior to the traditional higher-dose protocol, with fewer steroid side effects
With avacopan: Prednisone exposure can be reduced by approximately 60% (ADVOCATE protocol used a 20-week taper to zero)

The steroid paradox: Glucocorticoids are essential for acute disease control but cause significant harm with prolonged use. The entire direction of modern AAV research is toward minimizing steroid exposure. Ask your doctor about the planned steroid taper schedule.

Do you recommend rituximab or cyclophosphamide for my induction, and why?
Am I a candidate for avacopan to reduce my steroid dose?
What is the planned prednisone taper schedule? When can I expect to be off prednisone?
If my kidneys are involved, do I need IV pulse steroids?
Should I take anything to protect my bones while on steroids (calcium, vitamin D, bisphosphonate)?
Do I need fertility preservation before starting cyclophosphamide?
How will you monitor whether the treatment is working?
When will I transition from induction to maintenance therapy?

Avacopan (Tavneos) — Reducing Steroid Dependence

Avacopan was a major recent advance in AAV treatment — the first targeted therapy designed specifically for AAV, addressing the serious problem of long-term steroid toxicity. However, its safety and regulatory status changed significantly in 2026 — please read the alert below before considering or continuing this drug.

⚠ Important 2026 FDA safety alert — serious liver injury and a proposed withdrawal.

On March 31, 2026, the U.S. FDA warned that avacopan has been linked to serious and sometimes fatal liver injury. In reports the FDA reviewed, there were 76 cases of likely drug-related liver injury, including 54 hospitalizations and 8 deaths, and several cases of a rare condition called vanishing bile duct syndrome. On April 29, 2026, the FDA formally proposed withdrawing Tavneos from the U.S. market, citing concerns about both its liver risk and how effectiveness was measured in the original ADVOCATE trial. The manufacturer (Amgen) disagrees and the drug remains available for now while the FDA process plays out (public comment open through June 29, 2026); the European Medicines Agency has begun its own review.

What this means for you: Do not stop avacopan on your own — talk with your vasculitis specialist about whether to continue, given your individual situation. If you take avacopan, you should have regular liver blood tests. Seek medical care promptly for any signs of liver problems: yellowing of the skin or eyes, dark urine, pale stools, severe tiredness, loss of appetite, nausea/vomiting, pain in the upper-right abdomen, or easy bruising/bleeding. Because the situation is evolving, ask your doctor to confirm avacopan’s current FDA status before starting or refilling it. (Source: FDA Drug Safety Communication, March 31, 2026; FDA/CDER proposal to withdraw Tavneos, April 29, 2026.)

FDA-APPROVED The ADVOCATE trial (NCT02994927) enrolled 331 patients with active AAV and compared avacopan (added to rituximab or cyclophosphamide) versus standard prednisone taper. Key results:

Remission at 26 weeks: Avacopan was non-inferior to prednisone (72.3% vs. 70.1%)
Sustained remission at 52 weeks: Avacopan was SUPERIOR to prednisone (65.7% vs. 54.9%)
Kidney outcomes: Significantly better eGFR recovery in the avacopan group
Steroid exposure: The avacopan group received approximately 60% less cumulative prednisone

Dosing: 30 mg orally twice daily with food. Taken continuously for at least 52 weeks.

Key safety: Liver injury is the central concern. In the ADVOCATE trial liver-enzyme elevations were usually reversible, but serious and fatal drug-induced liver injury (and vanishing bile duct syndrome) have since been reported after approval — see the 2026 FDA safety alert above. Liver blood-test monitoring is mandatory. Avacopan does NOT replace rituximab or cyclophosphamide — it is added to standard immunosuppression.

Ask your doctor: “Am I a candidate for avacopan? If not, what is the plan to minimize my steroid exposure?” Avacopan may not be available everywhere due to cost (approximately $150,000–200,000/year list price in the US). Insurance coverage varies.

Maintenance Therapy — Preventing Relapse

Maintenance therapy is essential in AAV. Without it, relapse rates are very high — approximately 50% within 2 years for PR3-ANCA positive patients. Maintenance begins after remission is achieved (typically 3–6 months after starting induction).

GUIDELINE-SUPPORTED Rituximab maintenance is now the preferred approach for most AAV patients, based on MAINRITSAN, MAINRITSAN-2, and RITAZAREM data.

Fixed-schedule dosing: 500 mg IV every 6 months for at least 2 years (MAINRITSAN protocol)
ANCA/B-cell guided dosing: Rituximab given when ANCA rises or B cells return (MAINRITSAN-2). Uses less rituximab overall but requires regular monitoring
Duration: Minimum 2 years; many experts recommend 4 years or longer, especially for PR3-ANCA positive and relapsing disease
MAINRITSAN-3: Extended maintenance (4 years) reduced relapse risk further compared to 2 years

GUIDELINE-SUPPORTED Azathioprine (2 mg/kg/day orally) was the traditional maintenance agent before rituximab maintenance trials. It remains an acceptable alternative when rituximab is unavailable, unaffordable, or contraindicated.

Advantages: Oral, inexpensive, widely available
Disadvantages: Higher relapse rate than rituximab maintenance (approximately 29% vs. 5% at 28 months in MAINRITSAN)
TPMT testing: Must check thiopurine methyltransferase (TPMT) enzyme level before starting. Patients with low TPMT activity are at risk of severe bone marrow suppression.
Duration: Typically at least 2 years

Mycophenolate mofetil (MMF): Used as an alternative to azathioprine. The IMPROVE trial showed it was slightly less effective than azathioprine for preventing relapse, but it may be appropriate for some patients.
Methotrexate: Can be used for maintenance in non-renal, non-severe AAV. The WEGENT trial showed it was comparable to azathioprine for maintenance after non-severe GPA/MPA.

Critical warning: Do NOT stop maintenance therapy without discussing with your vasculitis specialist. The most common cause of preventable relapse is premature discontinuation of maintenance therapy. Even if you feel well, the disease can return silently and cause organ damage before symptoms appear.

Supportive Care During Treatment

AAV treatment involves powerful immunosuppressive drugs that require careful monitoring and prevention of side effects.

Pneumocystis prophylaxis (PJP): Trimethoprim-sulfamethoxazole (co-trimoxazole) one single-strength tablet daily or one double-strength tablet three times weekly is standard during induction and while on significant immunosuppression. This prevents a dangerous pneumonia caused by Pneumocystis jirovecii.
Vaccinations: Influenza (annually), pneumococcal, COVID-19, and hepatitis B vaccines should be given before starting rituximab if possible (rituximab blunts vaccine responses). Live vaccines are contraindicated during immunosuppression.
Immunoglobulin monitoring: Rituximab can cause hypogammaglobulinemia (low antibody levels) with prolonged use, increasing infection risk. IgG levels should be checked regularly. Some patients need immunoglobulin replacement therapy.
Hepatitis B screening: Must be done before rituximab. Rituximab can reactivate latent hepatitis B, which can be fatal. Patients with past hepatitis B exposure need antiviral prophylaxis during treatment.

Osteoporosis prevention: Calcium (1000–1200 mg/day), vitamin D (1000–2000 IU/day), and a bisphosphonate (e.g., alendronate) or denosumab for patients on prolonged glucocorticoids
Blood sugar monitoring: Glucocorticoids cause hyperglycemia. Monitor blood glucose regularly, especially in the first few weeks of high-dose steroids
Cardiovascular risk: AAV patients have increased cardiovascular risk. Monitor blood pressure, lipids, and glucose
Weight and diet: Steroid-induced weight gain is common. Maintaining a healthy diet and exercise regimen (as tolerated) is important

Regular kidney function tests: Creatinine, eGFR, urinalysis at every visit. Even during remission, kidney function should be monitored at least every 3–6 months
Blood pressure control: Target <130/80 mmHg. ACE inhibitors or ARBs are preferred for their kidney-protective properties
Avoid nephrotoxic drugs: NSAIDs (ibuprofen, naproxen) should generally be avoided. Inform all doctors that you have vasculitis-related kidney disease
Dialysis preparation: If kidney function continues to decline despite treatment, early referral for dialysis planning (fistula creation) and transplant evaluation is important. Kidney transplant is very successful in AAV when the disease is in remission.

Pregnancy & Family Planning

AAV often affects people during their reproductive years, and pregnancy is absolutely possible — but it needs planning. The single most important step is to raise family planning with your specialist early, ideally well before trying to conceive. Two things matter most: timing the pregnancy for a period of stable remission (many specialists suggest disease has been quiet for about 6–12 months), and reviewing your medications, because several AAV drugs can harm a developing baby and must be switched or stopped before conception.

Do not stop or change any medication on your own. Some drugs protect you from a dangerous flare, and stopping abruptly can be harmful. Plan changes with your rheumatology/nephrology team and a maternal–fetal medicine (high-risk obstetrics) specialist.

Always verify the latest guidance for your specific situation with your care team; this is a general summary.

Medication	During pregnancy	Breastfeeding
Cyclophosphamide	Not safe — can harm the baby and can affect future fertility. Reliable contraception required while taking it; ask about fertility preservation (egg or sperm banking) before treatment.	Not recommended
Methotrexate	Not safe — stop about 1–3 months before trying to conceive.	Not recommended
Mycophenolate (CellCept)	Not safe — stop at least 6 weeks before trying to conceive.	Avoid
Rituximab	Generally avoided in the 2nd and 3rd trimesters (can temporarily lower the baby’s immune cells). Reliable contraception during treatment and for ~12 months after; can sometimes be used earlier if disease requires — discuss timing.	Likely compatible (very little passes into milk); limited data
Azathioprine	Considered compatible — often the preferred maintenance drug during pregnancy (a TPMT blood test is checked first).	Compatible
Prednisone / steroids	Can be used at the lowest effective dose; your team will monitor blood pressure and blood sugar.	Compatible
Avacopan (Tavneos)	Limited human data — generally avoided; reliable contraception advised. (Also see the 2026 safety alert above.)	No data — avoid

Also for men: cyclophosphamide can reduce fertility, so ask about sperm banking before starting it if you may want children. Questions to ask your doctor: “Is my disease stable enough to plan a pregnancy?” · “Which of my medications need to change first, and when?” · “Should I see a high-risk pregnancy (maternal–fetal medicine) specialist before conceiving?”

Relapse Management

Relapse is unfortunately common in AAV, occurring in 30–50% of patients within 5 years even with maintenance therapy. Relapse rates are higher in PR3-ANCA positive patients and those with GPA. Early detection and treatment of relapse are critical to preventing organ damage.

Symptoms to watch for: Return of previous symptoms (nasal crusting, bloody nose, cough, joint pain, numbness), new symptoms, rising creatinine, blood in urine, new pulmonary nodules
Blood tests: Rising ANCA levels (especially PR3-ANCA), rising CRP/ESR, declining kidney function, active urine sediment
Major vs. minor relapse: A major relapse involves organ-threatening or life-threatening disease activity. A minor relapse involves symptoms without immediate organ threat. The treatment approach differs.

Major relapse: Re-induction with rituximab (preferred in relapsing disease based on RAVE) or cyclophosphamide, plus glucocorticoids. Consider avacopan to minimize steroid exposure.
Minor relapse: Increase in glucocorticoid dose and/or optimization of maintenance therapy. May not require full re-induction.
Rituximab for relapse: RAVE showed rituximab was superior to cyclophosphamide specifically in relapsing AAV. This makes rituximab the clear first choice for relapse treatment.
After relapse: Longer duration of maintenance therapy is recommended. If relapse occurred on azathioprine, switch to rituximab maintenance. If relapse occurred during rituximab maintenance, consider more frequent dosing or higher doses.

Is this a major or minor relapse?
Should I receive rituximab or cyclophosphamide for re-induction?
Was I on adequate maintenance therapy? Should the maintenance plan change?
How will you monitor for relapse going forward?
Has my cumulative cyclophosphamide dose reached a level where further use is concerning?
Is there a clinical trial I should consider?
How much additional kidney damage has this relapse caused?

Refractory Disease

A small percentage of AAV patients do not respond adequately to standard treatment (rituximab or cyclophosphamide) or relapse repeatedly despite optimal therapy. This is called refractory disease.

Switch between rituximab and cyclophosphamide: If one did not work, try the other
Avacopan addition: Adding avacopan may improve response in patients with inadequate response to standard therapy
IV immunoglobulin (IVIG): Can provide temporary disease control, particularly useful for patients with concurrent infections who need immunosuppression reduced
Clinical trials: Investigational agents including anti-CD19 therapies (obinutuzumab), anti-BAFF (belimumab for AAV), CAR-T approaches, and novel complement inhibitors are under investigation
Localized refractory disease: Some GPA manifestations (subglottic stenosis, orbital masses) may not respond to systemic therapy and require local treatments (dilation, intralesional steroids, surgery)

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Clinical Trials

Clinical trials are important in AAV because the disease is rare, treatments are still being optimized, and several promising new approaches are under investigation.

Trial	Agent(s)	Population	NCT Number
ADVOCATE (pivotal)	Avacopan (C5a receptor inhibitor)	Active AAV (GPA/MPA)	NCT02994927
RAVE (pivotal)	Rituximab vs. cyclophosphamide	Severe active GPA/MPA	NCT00104299
RITAZAREM	Rituximab vs. azathioprine maintenance	Relapsing AAV in remission	NCT01697267
PEXIVAS	Plasma exchange +/− reduced steroids	Severe AAV with renal/pulmonary involvement	NCT00987389
COMBIVAS	Rituximab + belimumab (sequential) vs. rituximab + placebo	PR3-ANCA AAV (mechanistic; recruitment closed)	NCT03967925
Various obinutuzumab trials	Anti-CD20 (next-gen rituximab)	Refractory/relapsing AAV	Search ClinicalTrials.gov for “obinutuzumab vasculitis”

ClinicalTrials.gov (clinicaltrials.gov): Search for “ANCA vasculitis” or “granulomatosis with polyangiitis”
Vasculitis Foundation: vasculitisfoundation.org — maintains a clinical trial database and patient registry
Vasculitis Clinical Research Consortium (VCRC): rarediseasesnetwork.org/vcrc — coordinates multi-center vasculitis trials across North America
Your vasculitis specialist: Many academic centers run trials not widely advertised. Ask about available studies.

International Access & Regulatory Landscape

AAV drug approvals and treatment approaches vary by country and region.

Drug	US FDA	EMA (Europe)	PMDA (Japan)	Notes
Rituximab (Rituxan)	Approved 2011 (GPA/MPA)	Approved 2013	Approved 2021	Biosimilars widely available, reducing cost. Standard of care globally.
Avacopan (Tavneos)	Approved Oct 2021; FDA proposed withdrawal Apr 2026	Approved Jan 2022; EMA review (2026)	Approved Sep 2021 (first in the world)	High cost limits access in some countries. 2026 FDA safety alert (serious/fatal liver injury) and proposed US withdrawal — see alert above; confirm current status with your doctor.
Cyclophosphamide	Generic (decades)	Available	Available	European practice favors IV pulse (CYCLOPS protocol) over daily oral.
Mepolizumab (Nucala, for EGPA)	Approved 2017 (EGPA)	Approved 2021 (EGPA)	Approved	For EGPA only, not GPA/MPA. Anti-IL-5 antibody.
Benralizumab (Fasenra, for EGPA)	Approved Sep 2024 (EGPA)	Approved (EGPA)	—	For EGPA only, not GPA/MPA. Anti-IL-5 receptor antibody; the second biologic approved for EGPA (MANDARA trial showed it was non-inferior to mepolizumab). 30 mg SC every 4 weeks.

ACR/Vasculitis Foundation 2021: American College of Rheumatology guidelines for AAV management
EULAR/ERA-EDTA 2022: European Alliance of Associations for Rheumatology guidelines
KDIGO 2024: Kidney Disease: Improving Global Outcomes guidelines for glomerulonephritis (includes AAV)
BSR/BHPR (UK): British Society for Rheumatology guidelines
Japanese College of Rheumatology: Japanese guidelines emphasize MPA management, which is more common in Japan. Japanese guidelines have historically favored longer maintenance and different steroid protocols.
EUVAS (European Vasculitis Society): Coordinates major European AAV trials (CYCLOPS, NORAM, IMPROVE, RITUXVAS, PEXIVAS)

EGPA — A Related Condition (Brief Overview)

This guide focuses on the two most common ANCA-associated vasculitides, GPA and MPA. The third member of the family, EGPA (eosinophilic granulomatosis with polyangiitis, formerly Churg-Strauss syndrome), is related but behaves differently — it centers on asthma, very high eosinophil counts, and allergic features alongside vasculitis, and only about 30–40% of people with EGPA are ANCA-positive. Because its biology and treatment differ, EGPA care should be guided by a specialist familiar with it; the summary below is orientation only.

Severe / organ-threatening disease (heart, gut, kidney, or nerve involvement): high-dose glucocorticoids, often with rituximab or cyclophosphamide, similar in spirit to GPA/MPA induction.
Eosinophil-driven, steroid-dependent, or relapsing disease (asthma/sinus-predominant): anti-IL-5 biologics are the major advance and help many people reduce steroids:
- Mepolizumab (Nucala): the first biologic FDA-approved for EGPA (2017), based on the MIRRA trial; given as an injection every 4 weeks.
- Benralizumab (Fasenra): FDA-approved for EGPA in September 2024 (the second biologic for EGPA), based on the MANDARA trial, which found it worked about as well as mepolizumab; also given by injection.
Avacopan and the GPA/MPA maintenance schedules on this page are not the standard framework for EGPA.

If you or a family member has EGPA specifically, ask for referral to a vasculitis or specialized allergy/immunology or rheumatology center.

Failed & De-Adopted Therapies

Understanding what has been tried and did not work helps evaluate new options and avoid outdated treatments.

DE-ADOPTED For decades, plasma exchange was considered standard for severe renal AAV and pulmonary hemorrhage. The PEXIVAS trial (NCT00987389), the largest AAV trial ever conducted (704 patients), definitively showed that plasma exchange did NOT reduce death or end-stage kidney disease. It is therefore no longer used routinely. However, it has not been abandoned entirely: current kidney guidelines (KDIGO 2024) still suggest considering plasma exchange for selected patients with the most severe kidney involvement (very high creatinine or needing dialysis) or with life-threatening lung bleeding (diffuse alveolar hemorrhage). The decision is individualized by your specialist.

FAILED The WGET trial (NCT00005007) tested etanercept added to standard therapy in GPA. It showed no benefit for remission maintenance and was associated with an unexpected increase in solid cancers. TNF inhibitors are not recommended for AAV.

INFERIOR The IMPROVE trial showed that mycophenolate mofetil had a higher relapse rate than azathioprine for maintenance therapy. While MMF may still be used for patients who cannot tolerate azathioprine, it is not preferred. Both are now superseded by rituximab maintenance.

DE-ADOPTED Historically, cyclophosphamide was continued for 12 months or longer. The CYCAZAREM trial showed that switching to azathioprine after 3–6 months of cyclophosphamide was equally effective and reduced cyclophosphamide toxicity. Modern protocols limit cyclophosphamide to 3–6 months maximum.

Why this matters: If someone suggests long-term cyclophosphamide, routine plasma exchange, or TNF inhibitors for your AAV, you now know the evidence does not support these approaches. Always ask: “What is the trial evidence for this approach?”

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Specialty Centers

AAV outcomes are measurably better at centers with dedicated vasculitis programs, experienced rheumatologists and nephrologists, and access to clinical trials. A second opinion from a vasculitis center is strongly recommended.

No endorsement. Listing a center here does not constitute an endorsement or recommendation. Trouvera has no financial relationship with any medical center listed unless explicitly disclosed. Patients should evaluate centers based on their own needs and in consultation with their medical team.

Referral Routing

Vasculitis Foundation: vasculitisfoundation.org — Find-a-Doctor tool, support groups, educational resources
Vasculitis Foundation helpline: 1-800-277-9474
Vasculitis Clinical Research Consortium (VCRC): rarediseasesnetwork.org/vcrc — Clinical trials, patient registry
National Organization for Rare Disorders (NORD): rarediseases.org

University of Utah — Division of Rheumatology

Academic rheumatology division with vasculitis expertise at an NCI-designated Comprehensive Cancer Center campus

Location: 30 N 1900 E, Salt Lake City, UT 84132
Phone: 801-581-7724 (rheumatology clinic); main hospital 801-581-2121
Programs: Vasculitis clinic, rheumatology fellowship, renal biopsy services. Associated with Huntsman Cancer Institute (801-585-0303) for complex immunology cases.

University of Utah — Division of Nephrology

Location: Salt Lake City, UT
Phone: 801-581-2121
Programs: Renal vasculitis management, glomerulonephritis clinic, kidney biopsy interpretation, dialysis and transplant referral.

Intermountain Health

Location: Multiple locations, Salt Lake City, UT
Phone: 801-442-2000
Programs: Rheumatology, nephrology, pulmonology services. Community-based multi-specialty network across Utah and the Intermountain West.

How to choose. University of Utah = Academic medical center with rheumatology and nephrology divisions experienced in vasculitis, biopsy services, and clinical trial access. Intermountain Health = Broad community-based network with rheumatology and nephrology, often in-network for local insurance.

Information verified May 2026. Availability changes — confirm with each institution directly.

Mayo Clinic Rochester

Location: Rochester, MN · Phone: 507-538-3270
Comprehensive vasculitis program. Dedicated vasculitis clinic. VCRC member site. Active AAV clinical trials.

Cleveland Clinic

Location: Cleveland, OH · Phone: 866-588-2264
Center for Vasculitis Care and Research. One of the largest vasculitis programs in the US. VCRC member site.

Massachusetts General Hospital / Rheumatology

Location: Boston, MA · Phone: 617-726-2000
Vasculitis and Glomerulonephritis Center. Major VCRC site. Active in RAVE, RITAZAREM, and other landmark AAV trials.

Johns Hopkins Vasculitis Center

Location: Baltimore, MD · Phone: 410-955-5000
Dedicated vasculitis center within rheumatology. Active research program. VCRC founding member.

Hospital for Special Surgery

Location: New York, NY · Phone: 212-606-1000
Vasculitis program within rheumatology division. Clinical trial access.

University of Pennsylvania Vasculitis Center

Location: Philadelphia, PA · Phone: 215-662-4000
Dedicated vasculitis program. VCRC member site. Active in AAV research.

VA Rheumatology Care

The VA system provides rheumatology and nephrology care through its network of medical centers. For complex vasculitis requiring specialized management, the VA partners with academic centers through community care arrangements. Veterans should ask their VA rheumatologist about:

Referral to an academic vasculitis center for second opinion
Community care authorization for specialized vasculitis management
Clinical trial access through VA-academic partnerships

VA Salt Lake City (Wahlen VAMC): 801-582-1565
VA Community Care: 1-877-881-7618

Mount Sinai Hospital — Vasculitis Clinic, Toronto

Location: 600 University Avenue, Toronto, ON M5G 1X5
Phone: 416-586-4800
Programs: One of Canada’s leading vasculitis programs. Active in clinical trials. VCRC member site.

St. Joseph’s Healthcare Hamilton

Location: Hamilton, ON
Phone: 905-522-1155
Programs: Vasculitis clinic. Active in Canadian vasculitis research networks.

Vasculitis Foundation Canada: vasculitis.ca
Kidney Foundation of Canada: 1-800-361-7494

International Centers of Excellence for AAV

Addenbrooke’s Hospital / University of Cambridge, UK: EUVAS coordinating center. Conducted PEXIVAS, CYCLOPS, and other landmark trials
Universitätsklinikum Freiburg, Germany: Major European vasculitis referral center
Hôpital Cochin, Paris, France: French Vasculitis Study Group coordinating center
University of Tokyo Hospital, Japan: Japanese vasculitis research. MPA is more prevalent in Japan, driving unique clinical expertise
St. Vincent’s Hospital, Melbourne, Australia: Australian vasculitis referral center

Caregiver Guidance

Caring for someone with AAV requires understanding the chronic nature of the disease, the side effects of treatment, and the importance of vigilance for relapse.

AAV is chronic. Unlike an infection that is treated and cured, AAV requires long-term management. Expect years of medication, regular blood tests, and specialist appointments.
Remission is not cure. When the disease is “in remission,” it means inflammation is controlled, not gone forever. Maintenance therapy and monitoring continue.
Steroid side effects are real. The mood changes, weight gain, insomnia, and irritability from high-dose prednisone are not character flaws — they are drug effects. They improve as the dose is tapered.
Fatigue is the most common complaint. Even in remission, many AAV patients experience significant fatigue. This is real, not laziness, and may require pacing activities.

Fever during immunosuppression: Can indicate serious infection. Seek medical attention promptly.
Return of vasculitis symptoms: Bloody nose, nasal crusting, cough, blood in urine, joint pain, numbness — may signal relapse
Blood in urine: Even if small amounts (pink-tinged urine), report to the medical team
New shortness of breath or coughing blood: Seek emergency care immediately

Vasculitis Foundation: 1-800-277-9474 — peer support, educational materials, annual conference
Vasculitis Foundation online community: vasculitisfoundation.org
Vasculitis UK: vasculitis.org.uk
Smart Patients Vasculitis Community: Online discussion forum for patients and caregivers

Glossary

AAV: ANCA-associated vasculitis. A group of autoimmune diseases (GPA, MPA, EGPA) that inflame small blood vessels.
ANCA: Anti-neutrophil cytoplasmic antibody. Autoantibodies that target proteins in neutrophils and cause vasculitis.
Avacopan (Tavneos): An oral complement C5a receptor inhibitor that reduces glucocorticoid use in AAV treatment.
BVAS: Birmingham Vasculitis Activity Score. A standardized tool used to measure disease activity in vasculitis.
Complement system: A group of blood proteins that help the immune system fight infection. In AAV, complement activation through the C5a pathway contributes to blood vessel damage. Avacopan blocks this pathway.
Crescentic glomerulonephritis: A severe form of kidney inflammation where crescent-shaped cellular proliferations form in the glomeruli. Hallmark of AAV kidney disease.
Cyclophosphamide: A potent immunosuppressive drug used for induction in severe AAV. Effective but carries risks of infertility and bladder cancer with prolonged use.
DAH: Diffuse alveolar hemorrhage. Bleeding into the lungs. A medical emergency in AAV.
eGFR: Estimated glomerular filtration rate. A measure of kidney function. Normal is above 90 mL/min. Below 15 indicates end-stage kidney disease.
EGPA: Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome). A related but distinct vasculitis associated with asthma and eosinophilia.
GPA: Granulomatosis with polyangiitis (formerly Wegener’s granulomatosis). A type of AAV that typically affects the upper airways, lungs, and kidneys.
Glucocorticoid: A class of steroid hormones (prednisone, methylprednisolone) used to suppress inflammation. Effective but causes significant side effects with prolonged use.
Induction therapy: Initial intensive treatment aimed at achieving remission by rapidly suppressing disease activity.
Maintenance therapy: Ongoing treatment after remission is achieved, aimed at preventing relapse.
MPA: Microscopic polyangiitis. A type of AAV that primarily affects kidneys and lungs without granulomatous inflammation.
MPO-ANCA: Myeloperoxidase ANCA. Autoantibodies targeting the MPO protein. Most common in MPA.
Pauci-immune: Little or no immune complex deposition seen on tissue biopsy. Characteristic of AAV kidney disease.
PR3-ANCA: Proteinase 3 ANCA. Autoantibodies targeting the PR3 protein. Most common in GPA. Associated with higher relapse risk.
Remission: Absence of active vasculitis symptoms and signs. Does not mean cure — relapse can occur.
Rituximab: A monoclonal antibody that depletes B cells. Used for both induction and maintenance in AAV.
RPGN: Rapidly progressive glomerulonephritis. A rapid decline in kidney function over days to weeks.
Subglottic stenosis: Narrowing of the airway below the vocal cords. A complication of GPA that may require ENT intervention.
Vasculitis: Inflammation of blood vessels. Can affect vessels of any size in any organ.

Sources and Further Reading

This guide draws on published medical literature, clinical trial records, and the work of rheumatologists, nephrologists, and vasculitis researchers across multiple countries. Key sources are listed below.

Primary Resources

PubMed (pubmed.ncbi.nlm.nih.gov) — Free public database of medical research
ClinicalTrials.gov (clinicaltrials.gov) — Authoritative registry of clinical trials
Vasculitis Foundation (vasculitisfoundation.org) — Patient education, support, advocacy (1-800-277-9474)
National Organization for Rare Disorders (NORD) (rarediseases.org) — Rare disease resources and patient assistance

Key Guideline and Trial References

ACR/VF 2021: Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of ANCA-Associated Vasculitis. Arthritis Rheumatol. 2021;73(8):1366–1383.
EULAR/ERA 2022: Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations on the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024;83(1):30–47.
RAVE: Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221–232. (NCT00104299)
ADVOCATE: Jayne DRW, Merkel PA, Schall TJ, et al. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021;384(7):599–609. (NCT02994927)
PEXIVAS: Walsh M, Merkel PA, Peh CA, et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med. 2020;382(7):622–631. (NCT00987389)
MAINRITSAN: Guillevin L, Pagnoux C, Karras A, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014;371(19):1771–1780.
RITAZAREM: Smith RM, Jones RB, Specks U, et al. Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease. Ann Rheum Dis. 2023;82(7):937–944. (NCT01697267)

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What This Guide Does Not Know

An honest guide names its own limits:

This guide cannot diagnose, stage, or treat anyone. It does not know your ANCA type, organ involvement, kidney biopsy results, or personal preferences. Only your medical team can build an actual plan.
AAV treatment is evolving. New trial results and guideline updates occur regularly. Every time-sensitive fact should be re-verified with your team.
Drug approvals and availability vary by country. This guide focuses primarily on FDA-approved therapies. Access differs in Europe, Japan, Canada, and other regions.
Individual outcomes cannot be predicted. Two patients with the same ANCA type and organ involvement can have very different courses.
This guide does not cover EGPA in depth. EGPA (eosinophilic granulomatosis with polyangiitis) is a related but distinct condition with different treatment approaches.

A final word. AAV is a frightening diagnosis, especially when organs like the kidneys and lungs are threatened. But the treatment landscape has improved enormously. Rituximab, avacopan, and improved steroid-sparing protocols mean that most patients achieve remission and many live normal lifespans. Get to a vasculitis specialist. Understand your ANCA type. Stay on maintenance therapy. Report new symptoms promptly. Bring this guide to your appointments. The Vasculitis Foundation (1-800-277-9474) connects you with other patients who understand your journey. You are not alone.