Clinical outcomes during the first three months posttransplant in renal allograft recipients managed by C2 monitoring of cyclosporine microemulsion.
BACKGROUND
MO2ART (monitoring of 2-hr absorption in renal transplantation) is the first prospective, multicenter trial of cyclosporine (CsA) blood level 2 hr postdose (C2) monitoring in de novo kidney recipients receiving CsA microemulsion (ME) (Neoral; Novartis, Basel, Switzerland). Efficacy and safety results from the first 3 months are presented here.


METHODS
MO2ART is a 12-month, open-label, randomized study involving 296 patients. In all patients, the dose of CsA-ME was adjusted to achieve protocol-defined C2 targets of 1.6 to 2.0 microg/mL for the first month, with subsequent tapering. Randomization into two target groups occurred at 3 months. All patients received steroids and mycophenolate mofetil (89%) or azathioprine. For patients with delayed graft function, the protocol permitted reduced C2 targets and prophylactic administration of antibodies.


RESULTS
At 3 months, overall incidence of biopsy-proven acute rejection was 11.5%. Median serum creatinine was 132 micromol/L. Patient and graft survival were 96.6% and 91.2%, respectively. C2 levels greater than 1.6 microg/mL were achieved within 5 days by 60.6% of patients with immediate graft function and 19.5% of patients with delayed graft function. Prophylactic antibodies were used in 15% of the total population. Twenty-four patients (8.1%) experienced serious adverse events with a suspected relation to CsA, and 26 patients (8.8%) discontinued the study because of adverse events (n=15) or after a switch in immunosuppression after rejection episodes (n=11).


CONCLUSIONS
Patient management by C2 monitoring resulted in a low incidence of biopsy-proven acute rejection in standard risk de novo kidney recipients, 85% of whom did not receive prophylactic antibodies. CsA-ME with C2 monitoring provides excellent short-term efficacy and safety among de novo renal transplant patients.
D000328:Adult; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D004655:Emulsions; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D015994:Incidence; D007408:Intestinal Absorption; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D012086:Reoperation; D015996:Survival Rate; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine