Real-world long-term outcomes and safety of avacopan for antineutrophil cytoplasmic antibody-associated vasculitis with advanced renal dysfunction: a multicenter cohort study (4U-AAV Study).

BACKGROUND: Avacopan is a promising steroid-sparing option for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV); however, its efficacy and safety in high-risk patients, such as those with severe renal dysfunction, remain unclear. METHODS: This retrospective observational study (4U-AAV study) analyzed adult patients newly diagnosed with AAV and ANCA-associated glomerulonephritis in six medical centers in Kyushu, Japan. Patients treated with avacopan were evaluated, and those receiving conventional therapy were used as a reference. The primary outcomes were all-cause mortality or initiation of maintenance renal replacement therapy, and the secondary outcomes included complete remission, AAV- or treatment-related complications, and drug-related adverse events. RESULTS: Seventy-four patients were enrolled, of whom 20 received avacopan. With avacopan, the median estimated glomerular filtration rate was 15.4 (interquartile range [IQR]: 9.2-38.0) mL/min/1.73 m2, and the median proteinuria was 3.2 (IQR: 1.2-6.3) g/gCr. During the 24-month follow-up, no deaths occurred in the avacopan-treated patients. The proportions of patients requiring maintenance kidney replacement therapy and achieving complete remission at 6 and 12 months appeared descriptively comparable to those receiving conventional treatment. The cumulative incidence of infections over 24 months was 16.2% with avacopan, whereas 50.2% with conventional treatment. Liver enzyme level elevation as adverse events was observed in 37.2% and 15.5% with avacopan and conventional treatment, respectively. CONCLUSION: In real-world practice, long-term renal outcomes of avacopan appeared descriptively comparable to those of conventional therapy in patients with AAV and renal dysfunction; however, elevated liver enzyme levels were frequent, highlighting the need for careful monitoring and further prospective studies.