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.