Mycophenolic acid area under the curve correlates with disease activity in lupus patients treated with mycophenolate mofetil

Abstract

Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil (MMF), which is widely used to treat systemic lupus erythematosus (SLE). In transplantation, MPA area under the plasma concentration-time curve from 0 to 12 hours (MPA AUC(0-12)) is correlated with clinical outcome. We undertook the present study to assess possible relationships between SLE activity and MPA AUC(0-12). Using a Bayesian estimator, MPA AUC(0-12) was determined in 71 consecutive SLE patients (61 women and 10 men; mean +/- SD age 34 +/- 10 years) receiving a stable MMF dose. On the same day, SLE activity was assessed using the SLE Disease Activity Index (SLEDAI; active disease defined as a SLEDAI score > or = 6) and the British Isles Lupus Assessment Group (BILAG) index (active disease defined as BILAG A or B). Two groups were studied: patients with active SLE (mean +/- SD SLEDAI score 11.6 +/- 4.4; n = 26) and patients with inactive SLE (mean +/- SD SLEDAI score 1.9 +/- 1.6; n = 45). MPA AUC(0-12) correlated weakly with the dose of MMF (r = 0.33, P = 0.005). Mean +/- SD MPA AUC(0-12) in the group with active SLE was significantly lower than that in the group with inactive SLE (26.8 +/- 13.6 microg.hour/ml versus 46.5 +/- 16.3 microg.hour/ml; P < 0.0001). MPA AUC(0-12) was negatively correlated with the SLEDAI (r = -0.64, P < 0.0001). In multivariate analysis, MPA AUC(0-12) was the sole parameter associated with SLE activity (odds ratio 0.89 [95% confidence interval 0.83-0.96], P = 0.002). The MPA AUC(0-12) threshold value of 35 microg.hour/ml was associated with the lowest risk of active SLE. Our data show that SLE activity is strongly correlated with MPA AUC(0-12). An individualized dosing regimen of MMF, with a target AUC(0-12) of 35 microg.hour/ml, should be considered for SLE patients.