Best of 2023: 2022 EULAR Recommendations for ANCA-associated Vasculitis Save

Editor's note: this article originally appeared March 16, 2023, and is being shared again as a Best of 2023. Enjoy!

EULAR has published the 2022 update on recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

AAV recommendations were last published in 2016, and since, research and clinical trials have advanced our understanding of AAV.  A EULAR task force of 20 experts from 16 countries, reviewed the literature and developed four overarching principles and 17 recommendations.

They recommend biopsies and ANCA testing are needed to assist in a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide.

They recommended steroid tapering within 4–5 months and that avacopan be considered to reduce steroid use in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. Rituximab may be used for remission and maintenance in GPA/MPA and patients with relapsing or refractory eosinophilic GPA, should consider the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV.

They defined Organ or Life-Threatening Manifestations: as glomerulonephritis, pulmonary haemorrhage, meningeal involvement, central nervous system involvement, retro-orbital disease, cardiac involvement, mesenteric involvement, and mononeuritis multiplex.

By contrast, manifestations not ultimately organ/life-threatening: includes nasal and paranasal disease, skin involvement without ulceration, myositis (skeletal muscle only), non-cavitating pulmonary nodules, and episcleritis.

Overarching principles

• Patients with AAV should be offered best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety and costs
• Patients with AAV should have access to education focusing on the impact of AAV and its prognosis, key warning symptoms and treatment (including treatment-related complications)
• Patients with AAV should be periodically screened for treatment-related adverse effects and comorbidities. We recommend prophylaxis and lifestyle advice to reduce treatment-related complications and other comorbidities
• AAV are rare, heterogeneous, and potentially life-threatening and organ-threatening diseases and thus require multidisciplinary management by centres with, or with ready access to, expertise in vasculitis

Recommendations

1. A positive biopsy is strongly supportive of a diagnosis of vasculitis and we recommend biopsies to assist in establishing a new diagnosis of AAV and for further evaluation of patients suspected of having relapsing vasculitis.
2. In patients with signs and/or symptoms raising suspicion of a diagnosis of AAV, we recommend testing for both PR3-ANCA and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing.
3. For induction of remission in patients with new-onset or relapsing GPA or MPA with organ-threatening or life-threatening disease, we recommend treatment with a combination of glucocorticoids and either rituximab or cyclophosphamide.* Rituximab is preferred in relapsing disease.
4. For induction of remission of non-organ-threatening or non-life-threatening GPA or MPA, treatment with a combination of glucocorticoids and rituximab is recommended. Methotrexate or mycophenolate mofetil can be considered as alternatives to rituximab.
5. As part of regimens for induction of remission in GPA or MPA, we recommend treatment with oral glucocorticoids at a starting dose of 50–75 mg prednisolone equivalent/day, depending on body weight. We recommend stepwise reduction in glucocorticoids according to table 4 and achieving a dose of 5 mg prednisolone equivalent per day by 4–5 months.
6. Avacopan in combination with rituximab or cyclophosphamide may be considered for induction of remission in GPA or MPA, as part of a strategy to substantially reduce exposure to glucocorticoids.
7. Plasma exchange may be considered as part of therapy to induce remission in GPA or MPA for those with a serum creatinine >300 µmol/L due to active glomerulonephritis.
   • Routine use of plasma exchange to treat alveolar haemorrhage in GPA and MPA is not recommended.
8. For patients with GPA or MPA with disease refractory to therapy to induce remission, we recommend a thorough reassessment of disease status and comorbidities and consideration of options for additional or different treatment. These patients should be managed in close conjunction with, or referred to, a centre with expertise in vasculitis.
9. For maintenance of remission of GPA and MPA, after induction of remission with either rituximab or cyclophosphamide, we recommend treatment with rituximab. Azathioprine or methotrexate may be considered as alternatives.
10. We recommend that therapy to maintain remission for GPA and MPA be continued for 24–48 months following induction of remission of new-onset disease.* Longer duration of therapy should be considered in relapsing patients or those with an increased risk of relapse, but should be balanced against patient preferences and risks of continuing immunosuppression
11. For induction of remission in new-onset or relapsing EGPA with organ-threatening or life-threatening manifestations, we recommend treatment with a combination of high-dose glucocorticoids and cyclophosphamide. A combination of high-dose glucocorticoids and rituximab may be considered as an alternative.
12. For induction of remission in new-onset or relapsing EGPA without organ-threatening or life-threatening manifestations, we recommend treatment with glucocorticoids.
13. For induction of remission in patients with relapsing or refractory EGPA without active organ-threatening or life-threatening disease, we recommend the use of mepolizumab.
14. For maintenance of remission of EGPA after induction of remission for organ-threatening or life-threatening disease, treatment with either methotrexate†, azathioprine‡, mepolizumab‡ or rituximab‡ should be considered
    • For maintenance of remission of relapsing EGPA after induction of remission for non-organ-threatening or life-threatening manifestations at the time of relapse, we recommend treatment with mepolizumab.
15. In the management of patients with AAV, we recommend that structured clinical assessment, rather than ANCA and/or CD19+ B cell testing alone, should inform decisions on changes in treatment.
16. In patients with AAV receiving rituximab, we recommend measurement of serum immunoglobulin concentrations prior to each course of rituximab to detect secondary immunodeficiency.
17. For patients with AAV receiving rituximab, cyclophosphamide and/or high doses of glucocorticoids, we recommend the use of trimethoprim–sulfamethoxazole as prophylaxis against Pneumocystis jirovecii pneumonia and other infections.