Reduced severe infection risk with avacopan in ANCA-associated vasculitis: a multicentre REVEAL cohort with time-varying exposure modelling

OBJECTIVES: To evaluate the association between avacopan (AVA) use and recurrent relapse and severe infection in patients with ANCA-associated vasculitis, with particular attention to time-varying treatment and glucocorticoid exposure. METHODS: In this multicentre retrospective cohort study, AVA use was modelled as a time-varying exposure. Stabilized inverse probability of treatment weighting was used to adjust for baseline differences. Recurrent relapse and severe infection, defined as an infection requiring hospitalisation, were analysed using time-dependent Cox proportional hazards models based on the Andersen-Gill formulation. Exploratory models additionally incorporated time-varying and cumulative prednisolone exposure. RESULTS: A total of 387 patients were included, of whom 52 received AVA and 335 did not. AVA exposure was associated with a lower estimated risk of severe infection (adjusted HR 0.22, 95% CI 0.07-0.68; P = 0.008), whereas no statistically significant difference in recurrent relapse risk was observed. AVA use was also associated with lower prednisolone exposure over time. This association with severe infection remained directionally consistent in glucocorticoid-adjusted models, although its magnitude varied depending on model specification. CONCLUSION: In this multicentre real-world cohort, AVA exposure was associated with a lower estimated risk of severe infection and reduced glucocorticoid exposure, whereas no statistically significant reduction in recurrent relapse risk was observed. These findings suggest that an AVA-containing treatment strategy may be associated with improved infection-related outcomes in routine practice, although the observational design precludes causal inference.