Mycophenolic acid trough level monitoring in solid organ transplant recipients treated with mycophenolate mofetil: association with clinical outcome.

BACKGROUND: Mycophenolate mofetil (MMF) is widely and successfully used in immunosuppressive regimens for the prophylaxis of organ rejection following transplantation. Conventionally, it is administered at a fixed dose without serial measurements of plasma concentrations of mycophenolic acid (MPA), the active metabolite. Recently, there has been an increased interest in therapeutic drug monitoring (TDM) of MMF therapy to optimize the benefit/risk index of the drug. Predose trough samples of MPA are considered most convenient and economic, thereby allowing an increased use of TDM in the transplant setting. However, the added value of TDM for MMF therapy is still under debate.
OBJECTIVE: This paper reviews (based on a systematic PubMed and EMBASE search, 1995-June 2006) the current evidence of the usefulness and clinical relevance of MPA trough level monitoring during MMF therapy in solid organ transplantation. FINDINGS AND
CONCLUSIONS: Based on data available in the public domain, the contribution of MPA trough level monitoring during MMF therapy in solid organ transplant recipients remains unproven. Available studies have limitations and report conflicting results. There is a lack of prospective randomized trials, particularly in pediatric renal transplant recipients and in cardiac and liver transplantation. While there is a suggestion that there may be a relationship between efficacy and MPA trough levels, the majority of studies showed no correlation between MPA plasma concentrations and adverse effects. Based on current evidence, the adherence to presently recommended target ranges for MPA troughs in solid organ transplantation cannot assure an improved clinical outcome with MMF therapy. Whether MPA trough level monitoring leads to improved efficacy and less toxicity is currently subject to a large randomized trial; final results are eagerly awaited.