Latest Treatment Strategies to treat ANCA Associated Vasculitis - ESENeph Exam Nephrology

The management of AAV is complex and requires a nuanced understanding of both the disease mechanisms and the latest treatment strategies. This blog post aims to synthesize the most recent guidelines from major nephrology and rheumatology bodies to aid nephrologists in making informed clinical decisions.

Introduction

ANCA-associated vasculitis (AAV) is a group of multisystem disorders characterized by inflammation and necrosis of small and medium blood vessels with unknown aetiology.

 

Guideline Summary

The NICE guideline for the management of adults with ANCA-associated vasculitis was developed in collaboration with the British Society for Rheumatology (BSR) and the British Health Professionals in Rheumatology (BHPR) Standards, Guidelines and Audit Working Group[1]. The guideline aims to provide recommendations for the management of adults with ANCA-associated vasculitis, which includes granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA)[2]. The target audience for this guideline is rheumatologists, nephrologists, general physicians, specialists, trainees, and nurse practitioners[1].

 

The guideline covers the diagnosis, assessment, and management of ANCA-associated vasculitis, with a focus on inducing remission, maintaining remission, and treating relapse when necessary[2]. The recommendations for induction therapy include high-dose glucocorticoids and cyclophosphamide, while maintenance therapy involves azathioprine or methotrexate to maintain remission[2]. The guideline also emphasizes the importance of regular monitoring for relapse and adverse effects of therapy[2].

 

The NICE guideline is part of a series of clinical practice guidelines that provide recommendations for the management of various conditions, including systemic vasculitis and ANCA-associated vasculitis[2]. The guideline is based on the latest evidence and is intended to improve the quality of care for patients with ANCA-associated vasculitis[2].

 

Example Scenarios

Here are some practical considerations and use case examples related to the management of ANCA-associated vasculitis (AAV):

 

Case 1: A 40-year-old patient presents with rapidly progressive glomerulonephritis (RPGN) and a serum creatinine of 4.5 mg/dL. ANCA testing is positive for PR3-ANCA, consistent with granulomatosis with polyangiitis (GPA).

 

Per the KDIGO 2024 guideline, this patient would be considered to have a severe AAV presentation requiring aggressive induction therapy. The recommended regimen would be:

 

- Rituximab 375 mg/m2 weekly for 4 weeks 

- OR Cyclophosphamide 0.67 g/m2 monthly for 3-6 months

- PLUS Glucocorticoids (e.g. methylprednisolone 1g IV for 3 days, then oral prednisone 1 mg/kg/day)

- Plasma exchange should be initiated promptly given the RPGN presentation

 

 

Case 2: A 60-year-old patient with PR3-GPA has achieved remission after 6 months of cyclophosphamide and high-dose glucocorticoids for induction. 

 

The NICE and KDIGO guidelines recommend transitioning to a maintenance immunosuppressive regimen:

 

- Azathioprine 2 mg/kg/day 

- OR Rituximab 1000 mg IV every 4-6 months

- PLUS a prolonged taper of low-dose glucocorticoids

 

Close monitoring for relapse with periodic ANCA testing and assessment of disease activity is crucial during the maintenance phase.

 

These cases illustrate how the latest guidelines can be applied to tailor induction and maintenance regimens based on disease severity and individual patient factors.

 

Controversies

Here are some of the key controversies and emerging areas of research in the management of ANCA-associated vasculitis (AAV):

 

1. Role of Plasma Exchange

While the KDIGO 2024 guideline recommends plasma exchange for patients with severe renal involvement or pulmonary hemorrhage, its role in non-severe AAV remains controversial. Some studies suggest plasma exchange may not provide additional benefit over immunosuppression alone in these cases.

 

2. Use of Avacopan

The KDIGO 2024 guideline introduces avacopan, a selective C5a receptor inhibitor, as an alternative to glucocorticoids for induction therapy. However, its long-term safety, efficacy compared to rituximab, and role in maintenance therapy are still being evaluated.

 

 

Emerging Research:

1. Biomarkers for Disease Activity

Current monitoring relies heavily on clinical assessment and ANCA titers, which can be imperfect markers of active vasculitis. Research is ongoing to identify novel biomarkers that can more accurately predict relapse and guide treatment decisions.

 

2. Novel Therapeutic Targets

With improved understanding of AAV pathogenesis, new therapeutic targets are being explored. These include complement inhibitors, granulocyte apheresis, and agents targeting specific cytokines like GM-CSF.

 

3. Personalized Medicine Approaches

Efforts are underway to develop predictive models that integrate clinical, genetic, and molecular data to guide individualized treatment selection and dosing in AAV patients.

 

4. Long-term Outcomes

As survival improves with modern therapies, more research is needed on strategies to mitigate treatment-related toxicities and improve quality of life for AAV patients.

 

These areas highlight the rapidly evolving landscape in AAV management, with potential for more targeted and personalized approaches in the future.

 

 

Citations:

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

[2] [PDF] NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE - NICE https://www.nice.org.uk/guidance/gid-ta10199/documents/draft-scope-pre-referral

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

[4] [PDF] Guidelines for the Management of ANCA-Associated Vasculitis https://www.nnuh.nhs.uk/publication/download/guidelines-for-the-management-of-anca-associated-vasculitis-v1-2/

[5] [PDF] Avacopan for treating anti-neutrophil cytoplasmic antibody-associated ... https://www.nice.org.uk/guidance/ta825/documents/draft-scope-post-referral

[6] [PDF] national institute for health and clinical excellence - NICE https://www.nice.org.uk/guidance/ta308/documents/vasculitis-antineutrophil-cytoplasmic-antibodyassociated-rituximab-with-corticosteroids-final-scope2

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

[8] Vasculitis (anti-neutrophil cytoplasmic antibody-associated) | Guidance https://www.nice.org.uk/guidance/ta308/documents/vasculitis-antineutrophil-cytoplasmic-antibodyassociated-rituximab-with-glucocorticoids-appraisal-consultation-document

[9] 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis - PubMed https://pubmed.ncbi.nlm.nih.gov/34235880/

[10] Vasculitis Foundation Treatment Options and Guidelines https://www.vasculitisfoundation.org/treatments-research/treatments/

[11] Vasculitis Clinical Practice Guidelines - American College of Rheumatology https://rheumatology.org/vasculitis-guideline

[12] Clinical Practice Guidelines - American College of Rheumatology https://rheumatology.org/clinical-practice-guidelines

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

[14] Executive summary of the KDIGO 2024 Clinical Practice ... - PubMed https://pubmed.ncbi.nlm.nih.gov/38388147/

[15] 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis - PubMed https://pubmed.ncbi.nlm.nih.gov/34235884/

[16] Overview | Rituximab in combination with glucocorticoids for treating anti ... https://www.nice.org.uk/guidance/ta308

[17] Executive summary of the KDIGO 2024 Clinical ... - Kidney International https://www.kidney-international.org/article/S0085-2538%2823%2900745-7/fulltext

[18] Executive summary of the KDIGO 2024 Clinical Practice Guideline for ... https://www.sciencedirect.com/science/article/pii/S0085253823007457

[19] 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.24634

[20] 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis - Maz https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.41774