Ab1261 Avacopan in the Treatment of Anca-Associated Vasculitis: Multicenter Prospective Real-Life Study on Efficacy, Safety, and Impact on Quality of Life

Background: Avacopan is a new orally administered drug approved for the treatment of ANCA-associated vasculitis (AAV). Objectives: The aim of this study was to assess efficacy, safety and impact on quality of life associated with the use of avacopan in a real cohort of patients from Italian Rheumatology Units. Methods: The prospective collection of clinical data commenced in May 2022, and encompassed patients with either GPA or MPA, including those with newly diagnosed or relapsing diseases, who initiated avacopan therapy. For each patient the Italian AAV-PRO questionnaire was completed every 3 months. Results: Twenty-four patients were included: 17 GPA (16/17 c-ANCA/PR3+; 1/17 p-ANCA/MPO+), 7 MPA (6/7 MPO+; 1/7 ANCA negative). The median age of patients was 60 (IQR 52-63) years, with 58% being women. One-third of the patients (8/24) initiated avacopan following a new diagnosis of AAV. Patients treated after a relapse (16/24) had a median disease duration of 8.5 (IQR 7-14) years and prior treatments with RTX (75%), CYC (50%), MTX (25%), AZA (18.8%), MMF (12.5%). At avacopan initiation, BVASv3 and VDI were 9 (IQR 5-20) and 3 (IQR 1-4), respectively. The main disease manifestations included renal involvement (75%), with 12/18 having rapidly progressive glomerulonephritis, and pulmonary involvement (46%), with 5/11 experiencing hemorrhagic alveolitis. Avacopan was administered in combination with RTX in all patients, preceded by CYC IV in 5 patients. Two out of 12 patients with rapidly progressive glomerulonephritis also underwent plasmapheresis. At the baseline, the median corticosteroid (CS) dose was 25 mg/day (IQR 7-41). For patients with renal involvement, the median baseline creatinine and proteinuria values were 1.9 mg/dL (IQR 1.6-2.8) and 1140 mg/24h (IQR 300-2400), respectively. Sixteen out of 18 patients had microhematuria. At 12 weeks, 75% of patients had achieved clinical remission, with 28% being steroid-free. The median CS dose had decreased to 5 mg/day (IQR 2-5) (p-value ). The median creatinine and proteinuria values had reduced to 1.6 mg/dL (IQR 1.2-2.1) (p-value=0.029) and 300 mg/24h (IQR 100-1223) (p-value=0.014), respectively. Only eight out of 18 patients still presented with microhematuria (p-value=0.005). During the observation period (median follow-up duration: 26 weeks IQR 22.5-52), avacopan was suspended 8 times, primarily due to infectious and adverse events (AEs): respiratory infections (50%), urinary tract infections (12.5%), diarrhea (12.5%), planned surgery (12.5%), and difficulty dispensing the drug (12.5%). Two clinical relapses were reported at weeks 26 and 52, necessitating the resumption of CS and RTX plus CS, respectively. One death at week 65 due to a fungal infection was registered. Finally, a progressive reduction in AAV-PRO questionnaire scores was observed from baseline to week 12 (Figure 1). Conclusion: The addition of avacopan to AAV induction therapy allows for a significant reduction in CS in the early weeks of treatment, with a good safety profile and positively impacting the perception of patients' quality of life. REFERENCES: 1 Jayne DRW et al, Avacopan for the Treatment of ANCA-Associated Vasculitis, N Engl J Med, 2021. Acknowledgements: NIL. Disclosure of Interests: None declared.