Concentration-controlled treatment of lupus nephritis with mycophenolate mofetil

Abstract

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. 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-AUC(0-12)) was assessed within a month after MMF initiation. After determination of MPA-AUC(0-12), MMF doses were titrated to achieve a target MPA-AUC(0-12) of 60-90 mg*h/l. After on average six months, MPA-AUC(0-12) measures were repeated to assess the effect of dose adjustment. One month after introducing MMF, MPA-AUC(0-12) was low and showed a high inter-individual variability. Dose adjustment with a target MPA-AUC(0-12) 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-AUC(0-12). 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 MPA-AUC(0-12). At 12 months of follow-up 87.5% of patients had achieved either partial (18.7%) or complete (68.8%) remission. Concentration-controlled dose adjustments with a target MPA-AUC(0-12) 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.