Therapeutic drug monitoring of mycophenolate mofetil in lupus nephritis patients during the maintenance phase

Abstract Mycophenolate mofetil (MMF) is a key therapy for proliferative lupus nephritis (LN), but wide interindividual variability in mycophenolic acid (MPA) exposure may affect efficacy and relapse risk. Identifying simple pharmacokinetic markers that accurately reflect overall drug exposure is essential to optimize treatment outcomes. This cross-sectional study included 100 adults with biopsy-proven class III/IV LN receiving standardized MMF maintenance therapy (2 g/day). Plasma MPA concentrations were measured at six time points (C₀, C₁, C₂, C₄, C₈, and C₁₂) using Enzyme Multiplied Immunoassay Technique (EMIT), and area under curve (AUC₀–₁₂) was calculated by non-compartmental analysis. Disease activity and cumulative organ damage were assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), respectively. Patients were classified as complete responders, partial responders, or non-responders/relapsers. Marked variability in MPA exposure was observed despite uniform dosing. AUC₀–₁₂ correlated most strongly with early post-dose C₁ levels. Complete responders had significantly higher AUC₀–₁₂ and C₁ values, whereas lower exposure was associated with relapse. Higher SLEDAI- 2 K scores, reduced C₁, and lower AUC₀–₁₂ independently predicted poor response. C₁ showed diagnostic accuracy comparable to AUC₀–₁₂ and superior to other time points. Early post-dose MPA concentration (C₁) is a reliable surrogate for total exposure and a strong predictor of treatment response, supporting its use for practical therapeutic drug monitoring in proliferative LN.