Glucocorticoid discontinuation and hepatic safety during avacopan treatment for antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study at a single center in Japan

Introduction Real-world data on glucocorticoid discontinuation and liver enzyme abnormalities during avacopan treatment remain limited, particularly in patients who initiate treatment later in the disease course. Methods We retrospectively studied 52 patients with microscopic polyangiitis or granulomatosis with polyangiitis who initiated avacopan at a single center in Japan. Glucocorticoid discontinuation was evaluated in 40 patients receiving systemic glucocorticoids at initiation, while liver enzyme abnormalities were assessed in all 52 patients. Time to glucocorticoid discontinuation was analyzed using Kaplan-Meier methods and Cox proportional hazards regression. Baseline factors associated with liver enzyme abnormalities were examined using univariable logistic regression. Results Glucocorticoid discontinuation during avacopan treatment was observed in 27 patients (68%), with a median time of 196 days (95% confidence interval, 37–355 days). Longer disease duration before avacopan initiation was associated with a lower rate of glucocorticoid discontinuation after adjustment for baseline prednisolone dose and disease activity (hazard ratio per year, 0.86; 95% confidence interval, 0.76-0.97; p = 0.017). Relapse occurred in five patients. Liver enzyme abnormalities during avacopan treatment were observed in 26 patients (50%). Treatment modification due to liver enzyme abnormalities was required in eight patients. Three permanently discontinued avacopan, four continued treatment after dose reduction, and one resumed treatment at a reduced dose after temporary interruption. Liver enzyme levels normalized in seven patients, while normalization was not assessed in one. Reduced-dose initiation was not significantly associated with liver enzyme abnormalities. Discussion In this Japanese single-center cohort, glucocorticoid discontinuation during avacopan treatment was observed in 27 of 40 patients, and a shorter disease duration before avacopan initiation was associated with more rapid discontinuation. Liver enzyme abnormalities were frequent and sometimes required treatment modification. These findings describe treatment patterns and clinical outcomes in routine practice but do not establish the efficacy, hepatic safety, or overall benefit-risk profile of avacopan.