High interpatient variability in response to mycophenolic acid maintenance therapy in patients with ANCA-associated vasculitis

摘要: BACKGROUND Mycophenolic acid (MPA) is used in the maintenance therapy of antineutrophil cytoplasm antibody-associated systemic vasculitis (AASV). MPA exerts its immunosuppression by inhibiting inosine 5'-monophosphate dehydrogenase (IMPDH), depleting activated lymphocytes guanine nucleotides and retarding their proliferation. The purpose our study was to examine correlation between clinical outcome pharmacokinetic-pharmacodynamic (PD) relationships patients with AASV. METHODS We studied 358 Caucasian control without any basal IMPDH activity. Thirty AASV under mycophenolate mofetil (MMF) underwent therapeutic drug monitoring. RESULTS observed a high interindividual variability regard activity treatment (0.8-35 nmol/mg protein/h). Patients were followed for mean (±SD) period 22 ± 8 months. During observation period, seven had relapse an elevated Birmingham Vasculitis Activity Score 9.2 6. (Abasal) who subsequently relapsed raised at baseline, before receiving first dose MMF, further increased time relapse, when compared stable patients. during significantly higher levels [IMPDH enzyme curve (AEC) (0-12)] than (P = 0.001), indicating inadequate suppression. MPA-AUC (0-12) decreased patients, contrast < 0.05). CONCLUSIONS Due highly variable response MPA, PD monitoring new tool detecting