Mycophenolic Acid Exposure in Lupus Nephritis: Correlation With Therapeutic Response and Adverse Events to Standard...

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, requires mycophenolate therapy. This observational study examined the correlation between exposure to mycophenolic acid (MPA) and clinical response in our setting, where therapeutic drug monitoring is not commonly practiced to make a case for its routine availability.

Adult patients with LN (≥18 years, histopathological classes III/IV/V), receiving standard mycophenolate mofetil (2-3 g/d), were stratified into induction and maintenance cohorts. Blood samples were collected at 0, 1, 2, 4, and 6 hours postadministration to assess MPA exposure (area under the ROC curve [AUC]0-12). The plasma samples were analyzed using high-performance liquid chromatography-ultraviolet detection. The AUC(0-12) was estimated using the formula: AUC0-12) = AUC0-6+(3*C6) + (3*C0).

Of 160 screened participants, 100 were enrolled (induction: n = 44; maintenance: n = 56). Complete and partial renal remission were achieved in 16% and 68% of patients, respectively, in the induction cohort. Higher MPA exposure correlated with sustained reductions in proteinuria. Those with complete renal response demonstrated a higher MPA-AUC0-12 h (42.6 ± 24.9 mcg·h/mL, 7/44) compared with the nonresponders (33.1 ± 22.3 mcg·h/mL, 7/44). The mean MPA-AUC0-12 h was 36.6 ± 20.3 mcg·h/mL in the maintenance cohort, and all 3 relapses occurred at levels considerably below 30 mcg·h/mL. The receiver operating characteristic analysis suggested a good discriminatory ability of 30 mcg·h/mL as the optimal threshold for inducing remission (AUC = 0.61, 95% CI: 52-0.71, P = 0.015), and 24 mcg·h/mL for maintaining remission (AUC = 0.91, 95% CI: 0.86-0.95, P = 0.0001). Most adverse events were mild to moderate in nature, and no serious adverse events were observed.

Our findings demonstrate that variability in MPA exposure significantly impacts treatment response outcomes in LN, reinforcing the clinical utility of therapeutic drug monitoring-guided, individualized mycophenolate mofetil therapy.