This is the lay version of the EULAR recommendations for the management of people with a type of
vasculitis associated with an antibody called antineutrophil cytoplasmic antibody. This name of this disease
is often shortened to ANCA-associated vasculitis, or AAV. The original publication can be downloaded from
the EULAR website: www.eular.org.
Introduction
EULAR gives advice to doctors, nurses, and patients about the best way to treat and manage diseases. In
2022, EULAR updated its recommendations on the management of AAV.
Doctors, nurses, other health professionals and patients worked together to develop this advice. The patients in the team ensured that the patient point of view was included.
What do we already know?
AAV is in fact a subgroup of diseases within the spectrum of primary systemic vasculitis. These include
granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). AAV is an autoimmune disease that causes inflammation in the small blood vessels.
This most commonly involves the upper airways, lungs, kidneys, eyes, and peripheral nerves, but almost any part of the body can be affected.
The EULAR recommendations on the management of people with small and medium vessel vasculitis were
first written in 2009, and updated in 2016 with a focus on AAV. Since that time there have been several new
clinical trials in AAV, and new treatments have been explored. The results of these have the potential to
change clinical care.
The updated recommendations also set out definitions of various disease activity states in AAV. Sometimes
these definitions can differ between clinical trials, which makes it hard to compare results. For the purpose of the recommendations, EULAR propose the following consensus definitions:
- Active disease: Presence of typical signs, symptoms, or other features of active AAV
- Remission: Absence of typical signs, symptoms, or features, with or without immunosuppressive
therapy - Sustained remission: Absence of typical signs, symptoms, or features over a defined time period,
with or without immunosuppressive therapy - Response: At least 50% reduction of disease activity score and absence of new manifestations
- Relapse: Recurrence of active AAV after a period of remission
- Refractory disease: Unchanged or increased signs, symptoms, or features after a period of
standard induction therapy. Damage, infections, side effects of treatment or co-morbidities as
potential causes of the persistent or worsened disease manifestations need to be ruled out.
What do the recommendations say?
In total, there are 4 overarching principles and 17 recommendations. The principles say that people with AAV should be offered best care based on shared decision making between the patient and the physician, and which includes consideration of efficacy, safety, and costs. People with AAV should have access to education so that they understand the impact of AAV, and can recognise key warning symptoms and complications. They also say that people should be screened every so often for treatment-related adverse effects and co-morbidities, and preventative treatment or lifestyle advice offered where needed. Finally, the overarching principles stress that AAV are rare, heterogeneous, and potentially life-and organ-threatening diseases which require multidisciplinary management by centres with – or access to – vasculitis experts.
Each recommendation is based on the best current knowledge from studies of scientific evidence or expert
opinion. The more stars a recommendation has the stronger the evidence is. However, recommendations
with limited scientific evidence may be important, because the experts can have a strong opinion even when the published evidence may be lacking.
One star (*) means it is a recommendation with limited scientific evidence.
Two stars (**) means it is a recommendation with some scientific evidence.
Three stars (***) means it is a recommendation with quite a lot of scientific evidence.
Four stars (****) means it is a recommendation supported with a lot of scientific evidence.
Recommendations
- Biopsies are recommended to establish a new diagnosis of AAV and to evaluate people who
might have relapsing vasculitis.**
A positive biopsy is strongly supportive of a diagnosis of vasculitis. A biopsy can also be helpful to
distinguish active disease from damage, or to work out the cause of clinical decline. However, it might
not be possible to do a biopsy in every person with suspected AAV. If you are unable to have a biopsy, or if it is delayed for some reason, treatment should be started while awaiting the biopsy results. - If you have signs or symptoms that raise suspicion of AAV, antibody tests are recommended.****
ANCA are detectable in most people with newly diagnosed GPA and MPA and contribute to the
diagnosis. However, the diagnosis should not be made on ANCA alone, as these antibodies can be
found in other inflammatory diseases and infections, or may be drug-induced. If AAV is suspected, you should be tested for both PR3- and MPO-ANCA using a high-quality antigen-specific assay. - To achieve remission in organ- or life-threatening disease new-onset or relapsing GPA or MPA,
you should receive treatment with a combination of glucocorticoids and either rituximab or
cyclophosphamide.**** Rituximab is preferred in relapsing disease.***
Treatment can help you achieve remission – where you do not have any signs or symptoms of your
disease. The choice of treatment will depend on your personal symptoms and disease severity. New
evidence has shown that a drug called rituximab can restore remission in people with relapsing disease. This may be used in combination with a course of steroids. Cyclophosphamide is also an option, but this drug can have long-term complications, and should not be used as a first choice in less severe disease. - To achieve remission of GPA or MPA which is not organ- or life-threatening, you should be
treated with a combination of glucocorticoids and rituximab. Methotrexate or mycophenolate
mofetil can be considered as alternatives to rituximab.***
If your disease does not pose an immediate danger to your organs or your life, then treatment should be started with steroids and rituximab. Other drugs called methotrexate or mycophenolate mofetil (often shortened to MMF) might be considered if your disease is new-onset. - If you have GPA or MPA your glucocorticoid starting dose will depend on your weight, but
should be gradually reduced over time.****
When oral glucocorticoids (steroids) are used, they should be started at a dose of 50–75 mg per day,
depending on your body weight. It is recommended that the dose is gradually reduced, aiming for 5 mg per day after 5 months. This is because taking a high dose of steroids for a long time can make you more likely to get infections or other side effects. - Avacopan in combination with rituximab or cyclophosphamide may be considered to induce
remission in people with GPA or MPA, as part of a strategy to reduce glucocorticoids.***
Avacopan is an oral drug that inhibits complement C5a receptor. It may be used to reduce your
exposure to steroid medicines. - If you have GPA or MPA and your serum creatinine is high due to active glomerulonephritis, you may be given plasma exchange.***
If your serum creatinine is more than 300 µmol/L due to active glomerulonephritis, your healthcare team may consider giving you plasma exchange. However, routine use of plasma exchange to treat alveolar hemorrhage in people with GPA or MPA is not recommended. - People with GPA or MPA that is refractory to therapy to induce remission should have a
thorough reassessment, and might be offered alternative treatments.*
People with refractory disease that does not respond to treatments aimed at inducing remission might
need to consider options for additional or different treatment. These people should have a thorough
reassessment of their disease status and any comorbidities. They should also be managed in close
conjunction with an expert centre, or be referred to somewhere with appropriate expertise - After achieving remission with either rituximab or cyclophosphamide, people with GPA or MPA
should continue treatment with rituximab; azathioprine or methotrexate may be considered.****
If you have achieved remission taking either rituximab or cyclophosphamide, your chances of sustained remission and overall survival are better if you carry on with treatment. This should be with rituximab, although azathioprine or methotrexate can also be considered as alternatives. - Therapy to maintain remission for GPA and MPA should be continued for 24 to 48 months after
achieving remission of new-onset disease.**** You might need treatment for longer than this if you have relapsing disease, but this should be balanced against your preferences and risks.*
Once you achieve remission, you will likely need to continue treatment for 2–4 years. A longer duration should be considered in relapsing patients or those with an increased risk of relapse. However, this should be balanced against your individual preferences and risks of continuing immunosuppression. - To induce remission in people with new-onset or relapsing EGPA with organ- or life-threatening manifestations treat with a combination of high-dose glucocorticoids and cyclophosphamide.***
If you have severe new-onset EGPA, you should be treated with a combination of high-dose steroids
and cyclophosphamide. A combination of high-dose steroids and rituximab may also be considered in
some people. - To induce remission in people with new-onset or relapsing EGPA without organ- or life-threatening manifestations, treat with glucocorticoids.***
Over 90% of people with EGPA without severe manifestations achieve remission when treated with
glucocorticoids. At the moment, there is no strong evidence to suggest a need for any other medication. - To induce remission in people with relapsing or refractory EGPA without active organ- or life-threatening disease, use mepolizumab.***
If your EGPA does not have severe or life-threatening manifestations, but is relapsing or refractory, you may be treated with a drug called mepolizumab instead of glucocorticoids. - Treatments to maintain remission of EGPA will vary depending on your disease.*
If you have achieved remission of an organ- or life-threatening EGPA, ongoing treatment with
methotrexate, azathioprine, mepolizumab, or rituximab should be considered. For people with non organ- or life-threatening manifestations at the time of relapse, treatment with mepolizumab is
recommended. - People with AAV should receive a structured clinical assessment to support treatment
decisions.***
Your structured clinical assessment should not be based on rather than ANCA and/or CD19+ B cell
testing alone. The results can be used to inform decisions on treatment changes. - People with AAV receiving rituximab should have their serum immunoglobulin concentrations
measured prior to each course of rituximab.***
This testing can help to detect any secondary immunodeficiency you may have. - If you are taking rituximab, cyclophosphamide, and or high-dose steroids for AAV, you may
need a preventative medicine against pneumonia and other infections.***
People taking rituximab, cyclophosphamide, and/or high doses of glucocorticoids should use
trimethoprim–sulfamethoxazole to protect them from Pneumocystis jirovecii pneumonia and other
infections.
Summary
Overall, these recommendations give guidance to health professionals and patients about the management
and treatment of people with AAV, based on the most recent evidence from clinical trials. However, there are still some knowledge gaps. This means it is important to work with your healthcare team to make an
informed decision about your disease and its treatment.
Recommendations with just one or two stars are based mainly on expert opinion and not backed up by
studies, but these may be as important as those with three or four stars.
If you have any questions or concerns about your disease or your medication, you should speak to a health
professional involved in your care.
