INTRODUCTION
Anti-neutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare autoimmune disease characterized by inflammatory necrosis of small blood vessels, including proteinase 3-ANCA and myeloperoxidase (MPO)-ANCA (1). Approximately 75%~90% of patients with AAV have renal involvement, often progressed to end-stage renal disease at definitive diagnosis (1,2).
Although substantial advances have been in cyclophosphamide therapy for AAV, treatment-related complications have increased. Mycophenolate mofetil (MMF) is recommended as an alternative to cyclophosphamide by EULAR/ERA-EDTA guidelines due to its good safety (3). Recently, the MYCYC trial has shown that MMF can be used as a first-line induction therapy for MPO-ANCA patients who have mild to moderate renal involvement without life-threatening extrarenal manifestations (4). ANCA-associated nephritis (AAN) with positive MPO may be a primary indication for administration of MMF (5).
Mycophenolic acid (MPA) is the active metabolite of MMF and mycophenolate sodium enteric-coated salt (EC-MPS). High inter-individual variability of MPA exposure has been widely reported in kidney transplant, stem cell transplant and autoimmune disease, leading to interest in population pharmacokinetic (PPK) model to identify the sources of variability (6). Unlike renal transplant recipients, patients with AAV had enhanced MPA clearance (CL), suggesting the need to comprehensively evaluate the role of disease factors on pharmacokinetics (7). Variability may be even more of a challenge in patients with AAV, who often have increased inflammatory markers, hypoalbuminemia and renal dysfunction, all of which can affect MPA levels (8,9).
To our knowledge, clinical trials on the variability of MPA in pediatric AAV are scarce, particularly the PPK of MPA for AAN children has not been described. This study aims to explore the factors contributing to pharmacokinetic variability of MPA and to optimize MMF dosage regimen in children with AAN.