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Avacopan for Treatment of ANCA-Associated Vasculitis
Quick Takes
- Avacopan, an orally administered C5a receptor antagonist, was noninferior to prednisone for inducing remission in ANCA-associated vasculitis.
- Avacopan was superior to prednisone at sustaining remission of ANCA-associated vasculitis for up to 52 weeks.
- By avoiding prolonged steroid tapers, avacopan may help to reduce prominent side effects from ANCA-associated vasculitis treatment.
Study Questions:
How does the C5a receptor antagonist, avacopan, compare to a tapering schedule of prednisone for the control of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis?
Methods:
Patients with ANCA-associated vasculitis were randomized at 143 international centers to receive either avacopan 30 mg twice daily or a prednisone taper for 20 weeks. This was a double-dummy, double-blind, controlled trial. All patients received either cyclophosphamide or rituximab. The co-primary endpoints were: 1) vasculitis remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 (scale 0-63) at week 26, and 2) sustained remission at week 52, defined as no glucocorticoid use in the prior 4 weeks.
Results:
A total of 331 patients underwent randomization, with a mean BVAS score of 16. Remission at week 26 (primary endpoint) occurred in 120/166 (72.3%) patients receiving avacopan and 115/164 (70.1%) patients receiving prednisone (p < 0.001 for noninferiority, p = 0.24 for superiority). Sustained remission at week 52 occurred in 109/166 (65.7%) patients receiving avacopan and 90/164 (54.9%) patients receiving prednisone (p < 0.001 for noninferiority, p = 0.007 for superiority). Serious adverse events occurred in 37.3% of patients receiving avacopan and 39.0% of patients receiving prednisone.
Conclusions:
The authors concluded that avacopan was noninferior to a prednisone taper with respect to remission at week 26 and superior to prednisone with respect to sustained remission at week 52.
Perspective:
Management of ANCA-associated vasculitis has long relied on lengthy steroid tapers, which have numerous toxic side effects. Avacopan, an orally administered small-molecule C5a receptor antagonist, blocks neutrophil chemoattraction and activation and has demonstrated efficacy at preventing ANCA-associated vasculitis complications in murine models. This trial demonstrated the efficacy of avacopan as compared to the current standard prednisone taper in management of ANCA-associated vasculitis. However, despite this advance in therapy, approximately one-third of patients were unable to achieve sustained remission. Nonetheless, reduction in overall glucocorticoid exposure is likely to lead to improvements in cardiovascular, infectious, psychological, endocrine, dermatologic, and ophthalmologic side effects. Further studies are needed to define the safety and efficacy profile beyond 52 weeks. Nonetheless, these results are promising for patients with newly diagnosed or relapsing ANCA-associated vasculitis.
Clinical Topics: Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Heart Failure and Cardiac Biomarkers
Keywords: Antibodies, Antineutrophil Cytoplasmic, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Cyclophosphamide, Glucocorticoids, Neutrophils, Prednisone, Receptor, Anaphylatoxin C5a, Secondary Prevention, Treatment Outcome, Vascular Diseases, Vasculitis
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