Real-World Experience with Avacopan in ANCA-Associated Vasculitis in Portugal

Abstract Introduction: Avacopan, a selective C5a receptor inhibitor, has emerged as a potential corticosteroid-sparing treatment in ANCA-associated vasculitis (AAV). This study aims to evaluate its real-world efficacy and safety in Portuguese patients with active AAV. Methods: We conducted a multicenter retrospective analysis of 15 adult patients with newly diagnosed or relapsing AAV treated with avacopan across nine academic centers in Portugal. Patients received avacopan 30 mg twice daily in conjunction with standard induction and maintenance therapy. Clinical outcomes, including Birmingham Vasculitis Activity Score (BVAS), prednisolone use, renal function, and adverse events, were assessed at 3, 6 and 12 months. Results: The median patient age was 65 (interquartile range (IQR): 51.5-75.5), and 60% had de novo AAV. Most patients (93.3%) presented with systemic manifestations, and renal involvement was seen in 60%. Median time to start avacopan was 3.45 months. Prednisolone was discontinued in eight patients, with a median time to cessation of 44 days post-avacopan initiation. Median BVAS at baseline, 3 and 12 months was 23 (13-28.5), 2 (2-4.5) and 0 (0-0), respectively. This consistent downward trend indicates effective disease control (p< 0.05). The median estimated glomerular filtration rate (eGFR) at baseline, 3 and 12 months was 15 (9-31), 38 (20-62) and 48 (36.5-83.5), respectively (n=9, p<0.05). Safety was generally acceptable; one patient discontinued avacopan due to reversible hepatotoxicity, and one died from sepsis. Conclusion: In this real-world Portuguese cohort, avacopan was effective in achieving and maintaining clinical remission in AAV, with a notable steroid-sparing effect. In this sample, we have shown the stability of eGFR in patients with renal involvement, a reduction in disease activity (BVAS improvement), a favorable safety profile, and the potential for use as maintenance monotherapy. These results support avacopan’s potential role in AAV management and warrant further investigation in larger prospective studies.