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Concentration-controlled treatment of lupus nephritis with mycophenolate mofetil

Daleboudt, G. M. N., Reinders, M. E. J., den Hartigh, J., Huizinga, T. W. J., Rabelink, A. J., de Fijter, J. W. & Berger, S. P., Feb-2013, In : Lupus. 22, 2, p. 171-179 9 p.

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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-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.

RESULTS: 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.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)171-179
Number of pages9
JournalLupus
Volume22
Issue number2
Publication statusPublished - Feb-2013
Externally publishedYes

    Keywords

  • Adult, Dose-Response Relationship, Drug, Female, Humans, Immunosuppressive Agents, Lupus Nephritis, Male, Mycophenolic Acid, Retrospective Studies, Young Adult, Journal Article

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