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Fixed‐ or Controlled‐Dose Mycophenolate Mofetil with Standard‐ or Reduced‐Dose Calcineurin Inhibitors: The Opticept Trial
Author(s) -
Gaston R. S.,
Kaplan B.,
Shah T.,
Cibrik D.,
Shaw L. M.,
Angelis M.,
Mulgaonkar S.,
MeierKriesche H.U.,
Patel D.,
Bloom R. D.
Publication year - 2009
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2009.02668.x
Subject(s) - medicine , calcineurin , mycophenolic acid , urology , adverse effect , tacrolimus , mycophenolate , regimen , clinical endpoint , single center , trough level , dosing , randomized controlled trial , gastroenterology , transplantation
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 (α= 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 ≤ 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.