Background: Mycophenolate mofetil (MMF) has recently been established as a potent drug in maintenance treatment for lupus nephritis. However, there is no consensus on the optimal dosing regimen because of a high inter-individual variability of mycophenolic acid (MPA), the active metabolite of MMF. This retrospective study aimed to investigate the effect of an individualized dosing regimen through concentration-controlled treatment on MPA exposure and renal outcome in patients with lupus nephritis. Methods: Sixteen patients with lupus nephritis and treatment with low-dose intravenous cyclophosphamide followed by MMF were included. MPA area under the plasma concentration-time curve from 0 to 12 hours (MPA-AUC0-12) was assessed within a month after MMF initiation. After determination of MPA-AUC0-12, MMF doses were titrated to achieve a target MPA-AUC0-12 of 60-90 mg*h/l. After on average six months, MPA-AUC0-12 measures were repeated to assess the effect of dose adjustment. Results: One month after introducing MMF, MPA-AUC0-12 was low and showed a high inter-individual variability. Dose adjustment with a target MPA-AUC0-12 of 60-90 mg*h/l resulted in individualized MMF dosing, significantly higher MPA-AUC 0-12 levels, and a non-significant reduction in variability of MPA-AUC0-12. Adverse effects were reported by 37.5% of patients, which resulted in a switch to azathioprine in two patients. There was no significant relationship between the occurrence of adverse effects and MPAAUC0- 12. At 12 months of follow-up 87.5% of patients had achieved either partial (18.7%) or complete (68.8%) remission. Conclusion: Concentration-controlled dose adjustments with a target MPA-AUC0-12 of 60-90 mg*h/l was associated with optimized MPA exposure and an excellent renal outcome at 12 months of follow-up in a small sample of SLE patients with lupus nephritis.

AUC, immunosuppression, lupus nephritis, mycophenolate mofetil, pharmacokinetics,
Department of Internal Medicine

Daleboudt, G.M.N, Reinders, M, Hartigh, J.D, Huizinga, T.W.J, Rabelink, A.J, de Fijter, J.W, & Berger, S.P. (2013). Concentration-controlled treatment of lupus nephritis with mycophenolate mofetil. Lupus, 22(2), 171–179. doi:10.1177/0961203312469261