An international group of researchers assessed the clinical usefulness of monitoring 2-hour post-dose cyclosporine (C2) levels in liver transplant recipients.
This was compared with using conventional trough cyclosporine blood levels (pre-dose) (C0).
A total of 307 de novo liver transplant patients, from 29 centers in 9 countries, were included in the study.
Cyclosporine oral therapy was initiated at 15 mg/kg/day and dose adjusted according to predetermined C2 or C0 target level ranges.
Baseline characteristics were similar between groups.
Graft loss at 12 weeks (retransplantation or death) occurred in 6.8% of C2 and in 7.0% of C0 patients.
Overall incidence of treated acute rejection was lower for C2 (24%) than C0 patients (32%).
In hepatitis C virus (HCV)-negative patients, the incidence of rejection in the C2 group was significantly less than in the C0 group (21% vs 33%).
However, in HCV-positive patients, the rejection rate was similar in both groups (27% for both groups).
| Overall incidence of acute cellular rejection was lower when using C2 monitoring.
C2 patients (n = 16) who reached minimum target cyclosporin levels by day 3 had a notably low incidence of rejection (13%).
However, there was no difference in the incidence of rejection in C0 patients, irrespective of time to reach target level.
For biopsy-proven acute rejections (22% for C2 vs 30% for C0), the incidence of moderate and severe histological diagnosis was significantly lower in the C2 group than in the C0 group (47% vs 73%).
Safety profiles were similar between the two groups, with few patient withdrawals due to adverse events (10% for C2; 7% for C0).
Dr Gary Levy, of the Toronto General Hospital, in Canada, said on behalf of his colleagues, "Using C2 monitoring, the overall incidence of acute cellular rejection was lower compared with the C0 group.
"In addition, the histological severity of acute rejections was shown to be significantly milder for the C2 group, indicative of good long-term prognosis."
"These data demonstrate that the use of C2 monitoring is superior to C0 and results in a reduction in the incidence and severity of acute cellular rejection, without detrimental effect on the drug safety profile," he concluded.