Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multi-system immune-mediated disease that frequently presents with reduced kidney function due to crescentic, necrotising glomerulonephritis (cGN) with or without inflammation in other organs and tissues. AAV presenting with cGN is typically treated with high-dose corticosteroid coupled with the cytotoxic agent cyclophosphamide (CYP) or the anti-B cell antibody rituximab (RITUX) – both of which achieve disease remission in a high proportion of patients. Maintenance of remission requires continued immunosuppressive therapy for 2 or more years and disease relapse, requiring re-treatment with CYP or RITUX occurs in 30-40% of patients. The long-term immunological consequences of the two primary therapeutic options for cGN due to AAV are not fully understood.
In this project, the electronic medical records (EMR) of all patients receiving CYP or RITUX treatment with at least 2 years of follow-up for cGN due to AAV in a tertiary referral Nephrology department during the past 10 years will be studied. Baseline and follow-up clinical and laboratory data reflecting patient demographics, treatment received, severity of kidney disease and indices of immunological health (white cell and white cell subtype counts, immunoglobulin levels, episodes and types of infection, development of cancer, occurrence of AAV relapse or other autoimmune disease) will be extracted and collated in a database. Primary analyses will compare patients treated with CYP or RITUX. Long-term consequences of the two therapies will be analysed by comparing longitudinal trends and number of events for indices of immunological health from 2 years following primary therapy to most recent follow-up. Outcomes for patients requiring re-treatment for AAV relapse will be compared to those of patients without relapse. Comparative analyses between the two groups will be adjusted for potential confounding variables. It is hypothesised that CYP is associated with a greater burden of long-term immunological deficits than RITUX.
