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

Arthritis Rheum. 2010 Jul;62(7):2047-54. doi: 10.1002/art.27495.


Objective: 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).

Methods: 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).

Results: 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.

Conclusion: 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.

MeSH terms

  • Adult
  • Area Under Curve
  • Female
  • Health Status
  • Humans
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use*
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Erythematosus, Systemic / physiopathology
  • Male
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacokinetics
  • Mycophenolic Acid / therapeutic use
  • Prospective Studies
  • Severity of Illness Index


  • Immunosuppressive Agents
  • Mycophenolic Acid