Fixed- or controlled-dose mycophenolate mofetil with standard- or reduced-dose calcineurin inhibitors: the Opticept trial

Am J Transplant. 2009 Jul;9(7):1607-19. doi: 10.1111/j.1600-6143.2009.02668.x. Epub 2009 May 20.


Mycophenolate mofetil (MMF) was developed with cyclosporine as a fixed-dose immunosuppressant. More recent data indicate a relationship between mycophenolic acid (MPA) exposure in individuals and clinical endpoints of rejection and toxicity. This 2-year, open-label, randomized, multicenter trial compared the efficacy and safety of concentration-controlled MMF (MMF(CC)) dosing with a fixed-dose regimen in 720 kidney recipients. Patients received either (A) MMF(CC) and reduced-level calcineurin inhibitor (MMF(CC)/CNI(RL)); (B) MMF(CC) and standard-level CNI (MMF(CC)/CNI(SL)); or (C) fixed-dose MMF and CNI(SL) (MMF(FD)/CNI(SL)). Antibody induction and steroid use were according to center practice. The primary endpoint was noninferiority (alpha= 0.05) of group A versus group C for treatment failure (including biopsy-proven acute rejection [BPAR], graft loss and death) at 1 year. Although mean CNI trough levels in group A did not reach the prespecified targets, they were statistically lower than those in groups B and C (p < or = 0.01 for each comparison). BPAR rates (8.5%) were low across groups. Group A had 19% fewer treatment failures (23% vs. 28%, p = 0.18). MMF doses were highest (p < 0.05), with withdrawals for adverse events the fewest (p = 0.02), in group A. Of the 80% of subjects taking tacrolimus (Tac), those with higher MPA exposure had significantly less rejection (p < 0.001) and diarrhea correlated with Tac, but not with MPA levels. Thus, MMF(CC) with low-dose CNI resulted in outcomes not inferior to those with standard CNI exposure and MMF(FD), indicating potential utility of MMF(CC) in CNI-sparing regimens.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Calcineurin Inhibitors*
  • Cyclosporine / administration & dosage
  • Cyclosporine / adverse effects
  • Female
  • Glomerular Filtration Rate / drug effects
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacokinetics
  • Kidney Transplantation* / immunology
  • Kidney Transplantation* / physiology
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacokinetics
  • Prospective Studies
  • Tacrolimus / administration & dosage
  • Tacrolimus / adverse effects
  • Treatment Outcome


  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Mycophenolic Acid
  • Tacrolimus