Avacopan is a small-molecule complement 5a receptor (C5aR or CD88) antagonist approved by the United States Food and Drug Administration as an adjunctive therapy in combination with immunosuppressants and corticosteroids for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. By selectively inhibiting the C5a receptor, avacopan blocks neutrophil chemoattraction, activation, and adhesion while preserving other beneficial complement pathways. This selective mechanism represents a significant advancement in the management of ANCA-associated vasculitis, as conventional corticosteroid-based regimens are often linked to substantial adverse effects and reduced quality of life, along with a risk of relapse.
A recent study published in RMD Open found that avacopan demonstrated similar remission rates to prednisone taper in patients with antineutrophil cytoplasmic antibody-associated vasculitis receiving cyclophosphamide, while showing a numerically lower relapse rate, greater improvement in kidney function, faster albuminuria reduction, and reduced glucocorticoid-related toxicity with comparable safety.
The study evaluated efficacy and safety of avacopan versus a prednisone taper in the subgroup of patients with granulomatosis with polyangiitis or microscopic polyangiitis receiving cyclophosphamide followed by azathioprine or mycophenolate mofetil in the ADVOCATE trial. The phase 3 randomized ADVOCATE trial previously demonstrated that avacopan was non-inferior to prednisone taper in achieving remission at week 26 and superior in sustaining remission at week 52 in patients receiving rituximab or cyclophosphamide induction therapy.
Of 330 patients receiving study medication, 116 received cyclophosphamide, with 59 patients in the avacopan group and 57 in the prednisone taper group. Key efficacy outcomes were remission at week 26 and sustained remission at week 52. Additional outcomes included glucocorticoid toxicity, estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, and safety.
Remission at week 26 was achieved by 62.7% of patients in the avacopan group and 59.6% in the prednisone taper group. Sustained remission at week 52 was observed in 55.9% of patients receiving avacopan and 52.6% receiving prednisone taper. Over 52 weeks, relapses occurred in 13.0% of the avacopan group compared with 22.6% in the prednisone taper group.
The avacopan regimen was associated with improved kidney function, demonstrated by higher estimated glomerular filtration rate and faster reduction of albuminuria, along with reduced glucocorticoid-related toxicity compared with prednisone taper. Serious adverse events were comparable between groups (55.9% in the avacopan group vs. 56.1% in the prednisone taper group). Treatment with avacopan combined with a markedly reduced glucocorticoid regimen also led to greater improvements in health-related quality of life, while maintaining a similar overall safety profile.
These results support the use of avacopan in combination with cyclophosphamide for the management of granulomatosis with polyangiitis or microscopic polyangiitis, offering a glucocorticoid-sparing option that effectively controls vascular inflammation and reduces the long-term complications associated with steroid therapy, such as infections, diabetes, and osteoporosis. Overall, avacopan represents a promising addition to the treatment arsenal for ANCA-associated vasculitis, providing durable remission and improved patient outcomes.
References
- Geetha D, Neumann T, Karras A, Cid MC, Merkel PA, Bray S, Bozeman AM, Jayne DRW; Members of the ADVOCATE Study Group. Efficacy and safety of avacopan for treatment of patients with ANCA-associated vasculitis receiving cyclophosphamide. RMD Open. 2025 Oct 5;11(4):e005743.
- Garg J, Frishman WH. AVACOPAN: A New Adjunctive Therapy for Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Cardiol Rev. 2023 Jan-Feb 01;31(1):3-6.