Latest 2024 guidelines for the management of ANCA-associated Vasculitis

Here is a comprehensive blog post on the latest guidelines for the management of ANCA-associated vasculitis (AAV), based on the attached KDIGO 2024 guideline

Outline:

1. Introduction to ANCA-associated vasculitis (AAV)

2. Key recommendations from latest guidelines 

3. Diagnosis of AAV

4. Prognosis of AAV

5. Treatment of AAV

- Induction therapy

- Maintenance therapy

- Treatment of relapsing disease

6. Special situations 

- Refractory disease

- Transplantation

7. Practical considerations and use case examples

8. Controversies and emerging research

9. Discussion comparing guidelines

10. References

 

 

Key Recommendations:

- Glucocorticoids plus rituximab or cyclophosphamide are recommended for initial treatment of new-onset AAV (KDIGO 2024, 1B)

- Maintenance therapy with rituximab or azathioprine plus low-dose glucocorticoids is recommended after induction of remission (KDIGO 2024, 1C)

- Patients with relapsing disease should be reinduced, preferably with rituximab (KDIGO 2024, practice point)

- Transplantation should be delayed until patients are in complete remission for ≥6 months (KDIGO 2024, practice point)

 

 

Introduction:

ANCA-associated vasculitis (AAV) is a group of autoimmune diseases characterized by inflammation and damage to small blood vessels. The major forms are granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). AAV frequently involves the kidneys, lungs, upper airways, skin, and nervous system. Untreated, AAV has a poor prognosis, but survival has improved with the use of immunosuppressive therapy. However, both AAV and its treatment are associated with considerable morbidity. Recently, several guidelines have been published with evidence-based recommendations for the management of AAV.

 

 

Diagnosis:  

The diagnosis of AAV is based on a compatible clinical presentation along with detection of ANCA (anti-PR3 or anti-MPO antibodies) and histologic evidence of pauci-immune vasculitis, typically necrotizing and crescentic glomerulonephritis on kidney biopsy. However, treatment should not be delayed while awaiting biopsy results in patients with active disease, especially if rapidly progressive glomerulonephritis is present (KDIGO 2024, practice point). Patients with suspected AAV should be referred to a center with experience in managing these complex cases.

 

 

Prognosis:

Factors associated with worse prognosis in AAV include older age, kidney involvement, and pulmonary hemorrhage. Achieving remission improves survival. Patients with PR3-ANCA are more prone to relapse than those with MPO-ANCA. Rising ANCA titers may predict relapse. Chronic kidney damage from prior inflammation confers a poor long-term renal prognosis.

 

 

Treatment - Induction:

For induction of remission in new-onset disease, the KDIGO 2024 guideline recommends treatment with glucocorticoids in combination with either rituximab or cyclophosphamide (1B recommendation). Specific dosing regimens are provided in the guideline. In patients with severe kidney dysfunction (SCr >4 mg/dL), rituximab data is limited, so a combination of rituximab and cyclophosphamide can be considered. Avacopan, a C5a receptor inhibitor, is a potential alternative to glucocorticoids, especially for patients at high risk of steroid toxicity. Plasma exchange may be beneficial in severe cases, particularly those with diffuse alveolar hemorrhage or requiring dialysis.

 

 

Treatment - Maintenance:  

To maintain remission after induction, the KDIGO 2024 guideline recommends ongoing immunosuppression with either rituximab or azathioprine, in combination with low-dose glucocorticoids (1C recommendation). The optimal duration of maintenance therapy is 18-24 months after stable remission is achieved. Rituximab is preferred for relapsing or PR3-positive patients. Methotrexate and mycophenolate are alternative options in case of intolerance to first-line agents.

 

 

Relapsing Disease:

Patients experiencing a relapse of AAV should be reinduced with immunosuppression, preferably using rituximab, according to the KDIGO 2024 guideline. Minor relapses may be treated by increasing glucocorticoids and optimizing maintenance immunosuppression.

 

 

Special Situations:

For refractory cases not responding to standard therapy, the KDIGO guideline suggests treatment escalation by adding rituximab to cyclophosphamide (or vice versa), increasing glucocorticoids, and/or using plasma exchange. In patients with end-stage kidney disease due to AAV who are transplant candidates, transplantation should be delayed until the patient has been in complete remission for at least 6 months.

 

 

Practical Considerations and Use Cases:

- A 60-year-old man is diagnosed with MPO-ANCA vasculitis and biopsy-proven pauci-immune glomerulonephritis (SCr 2.5 mg/dL). Induction therapy with rituximab (375 mg/m2 weekly x4) and glucocorticoids is initiated. After achieving remission, he is maintained on rituximab (500 mg every 6 months) and low-dose prednisone is slowly tapered off over 6 months.

 

- A 40-year-old woman with a history of relapsing PR3-ANCA vasculitis presents with rising creatinine and active urine sediment. She is reinduced with rituximab (1000 mg x2 doses) and glucocorticoids. Maintenance therapy with rituximab 1000 mg every 4 months is continued for 2 years after remission.

 

 

Controversies and Emerging Research:

The optimal duration and tapering protocol for glucocorticoids in AAV remains controversial. Lower-dose regimens are being studied to minimize toxicity. The role of plasma exchange is debated, with the PEXIVAS trial showing no overall benefit, but potential efficacy in severe kidney disease. Avacopan is a promising steroid-sparing agent but requires further long-term safety data. Newer therapies targeting alternative pathways (e.g. complement) are under investigation.

 

 

Discussion:  

The KDIGO 2024 guideline provides updated evidence-based recommendations largely consistent with other recent guidelines from EULAR/ERA, BSR, and ACR. The key areas of agreement include the central role of rituximab and cyclophosphamide for induction, use of maintenance immunosuppression to prevent relapse, and a general trend towards minimizing glucocorticoid exposure. The guidelines differ slightly in the details of dosing regimens and use of plasma exchange. Overall, the management of AAV requires an individualized approach based on the patient's disease severity, ANCA type, relapse risk, and comorbidities. Ongoing research aims to optimize therapy while reducing treatment-related toxicity.

 

 

References:

1. KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis. Kidney Int. 2024;105(3S):S71-S116.

2. Chung SA, 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. 

3. Suppiah R, et al. Peripheral neuropathy in ANCA-associated vasculitis: outcomes from the European Vasculitis Study Group trials. Rheumatology (Oxford). 2011;50(12):2214-2222.

4. Walsh M, et al. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020;382(7):622-631.

5. Jayne DRW, et al. Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis. J Am Soc Nephrol. 2017;28(9):2756-2767.

 

Citations:

[1] KDIGO-2024-ANCA-Vasculitis-Guideline-Update.pdf https://ppl-ai-file-upload.s3.amazonaws.com/web/direct-files/1359706/671261f3-497b-4f4d-9bfc-4d1fa202a694/KDIGO-2024-ANCA-Vasculitis-Guideline-Update.pdf

[2] BSR and BHPR guideline for the management of adults with ANCA ... https://academic.oup.com/rheumatology/article/53/12/2306/1802843

[3] [PDF] NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE - NICE https://www.nice.org.uk/guidance/ta825/documents/final-scope

[4] KDIGO 2024 Clinical Practice Guideline for the Management of ... https://pubmed.ncbi.nlm.nih.gov/38388102/

[5] EULAR recommendations for the management of ANCA-associated ... https://ard.bmj.com/content/83/1/30

[6] KDIGO Announces Publication of the 2024 Clinical Practice ... https://kdigo.org/kdigo-announces-publication-of-the-2024-clinical-practice-guideline-for-antineutrophilic-cytoplasmic-antibody-anca-associated-vasculitis/

[7] Antineutrophilic Cytoplasmic Antibody (ANCA)-Associated Vasculitis https://kdigo.org/guidelines/antineutrophilic-cytoplasmic-antibody-anca-associated-vasculitis-aav/

[8] Guidelines for Vasculitis https://www.vasculitis.org.uk/professionals/guidelines-vasculitis

[9] 2022 American College of Rheumatology/European Alliance of ... https://pubmed.ncbi.nlm.nih.gov/36382396/

[10] KDIGO 2023 ANCA Guideline Update Available for Public Review https://kdigo.org/kdigo-2023-anca-guideline-update-available-for-public-review/