When is avacopan used in Anti-Neutrophil Cytoplasmic Antibody (ANCA) vasculitis

From the Guidelines

Avacopan is used in Anti-Neutrophil Cytoplasmic Antibody (ANCA) vasculitis as an alternative to glucocorticoids for induction of remission, particularly in patients at increased risk of glucocorticoid toxicity or with lower kidney function (eGFR <20 ml/min per 1.73 m2).

Key Points

• Avacopan has been shown to be an effective alternative to glucocorticoid treatment in AAV, with potential to improve kidney outcomes 1.
• The recommended dose of avacopan is 30 mg twice daily, as used in the ADVOCATE trial 1.
• Avacopan may be considered for induction of remission in GPA or MPA, as part of a strategy to substantially reduce exposure to glucocorticoids, especially in patients with increased risk of glucocorticoid toxicity, such as those with high infection risk, preexisting diabetes mellitus, psychiatric disorders, and osteoporosis 1.
• Patients with lower kidney function (eGFR <20 ml/min per 1.73 m2) may benefit from avacopan, as it has been shown to lead to an increased recovery of kidney function in these patients 1.
• The use of avacopan is limited by financial considerations and lack of long-term data, and its use should be individualized based on patient-specific factors 1.

From the FDA Drug Label

The efficacy and safety of TAVNEOS was evaluated in a double-blind, active-controlled, phase 3 clinical trial (NCT02994927) in 330 patients with newly diagnosed or relapsed ANCA-associated vasculitis Remission at Week 26 and Sustained Remission at Week 52 Remission was achieved by 72.3% of patients in the TAVNEOS group and 70.1% of patients in the prednisone group at Week 26 At Week 52, a significantly higher percentage of patients had sustained remission in TAVNEOS group (65.7%) compared to the prednisone group (54. 9%)

Avacopan is used in ANCA-associated vasculitis for patients with newly diagnosed or relapsed disease, as part of a treatment regimen that includes standard immunosuppressive regimens such as cyclophosphamide, rituximab, or mycophenolate mofetil. The goal of avacopan treatment is to achieve disease remission and sustained remission. Key points about avacopan use in ANCA-associated vasculitis include:

• Indications: newly diagnosed or relapsed ANCA-associated vasculitis
• Treatment regimen: avacopan 30 mg twice daily for 52 weeks, plus standard immunosuppressive regimens
• Goals of treatment: disease remission and sustained remission 2

From the Research

Avacopan in ANCA-Associated Vasculitis

• Avacopan is used in the treatment of ANCA-associated vasculitis (AAV) as a steroid-sparing agent, reducing the cumulative dosage of glucocorticoids (GC) 3.
• The use of avacopan in AAV is recommended in international guidelines as a possible solution for reducing GC-toxicity in AAV patients 3.
• Avacopan has been shown to be effective in achieving disease remission and improving renal function in patients with ANCA-associated vasculitis, with a reduced risk of adverse events compared to prednisone 4, 5, 6.

Clinical Trials and Evidence

• The ADVOCATE trial, a phase III randomized double-blind placebo-controlled clinical trial, demonstrated that avacopan was noninferior to prednisone taper with respect to remission at week 26 and superior to prednisone taper with respect to sustained remission at week 52 5, 6.
• Avacopan has been shown to be effective in conjunction with standard therapy, including cyclophosphamide or rituximab, in achieving clinical remission in AAV patients 4, 5, 6.
• The safety and clinical effects of avacopan beyond 52 weeks have not been fully addressed in clinical trials 5, 6.

Recommendations and Guidelines

• The Canadian Vasculitis Research Network (CanVasc) has published recommendations for the use of avacopan in AAV, including guidance on therapy indication and duration, as well as timely glucocorticoid tapering 7.
• Avacopan is recommended as a steroid-sparing agent for the management of AAV, with the goal of reducing GC-toxicity in AAV patients 3.