Patient management by cyclosporine C2 monitoring.

Abstract

Campbell and Johnson (1) are correct in saying that there have been no prospective clinical trials reported of predose concentration (C0) versus 2-hr concentration (C2) for the therapeutic drug monitoring of cyclosporine in renal transplant patients. However, there are at least two studies in which the use of C0 and C2 were directly compared in other transplant indications (2,3). These studies showed that, in both liver (2) and heart (3) transplant patients, there was a clinical benefit to be gained from using C2 rather than C0 monitoring. Nevertheless, Campbell and Johnson’s main concern with C2 monitoring is the lack of supporting clinical trial data. However, if they were to examine the scientific evidence that supports the use of C0 monitoring for cyclosporine, they would find that it is entirely observational (4), and this is true of therapeutic drug monitoring in general (5). We do not believe they will find a prospective trial of C0 monitoring versus no monitoring, or a comparison of two (or more) different concentration targets for C0, in the literature. A major survey of the target predose concentrations used in over 40 transplant centers demonstrated a wide variation between centers (6). Although some of the variation was attributable to differences in the organ transplanted and the time posttransplant, centers using the same immunosuppressive protocol exhibited marked differences in the target concentrations used. For example, at the time of the survey, two Canadian centers were using the same triple immunosuppression regimen of cyclosporine, prednisone, and azathioprine in renal transplant patients, but the centers had different target C0 concentrations for cyclosporine (6). Nonetheless, despite these real differences, the C0 concentration is still widely used in clinical practice to monitor cyclosporine therapy. In de novo kidney transplant patients, C2 monitoring in the MO2ART (Monitoring Of 2 hour Neoral Absorption in Renal Transplantation) trial has resulted in the lowest ever biopsy-proven rejection rate seen at 3 months (11.9%) in any multicenter trial of cyclosporine-based triple therapy (7). Data such as these, and the consensus supporting C2 monitoring presented by Levy et al. (8), make C2 monitoring somewhat more than an “interesting hypothesis.” However, we would agree with Campbell and Johnson that C2 monitoring warrants further study, particularly in long-term “stable” renal transplant recipients. To this end, we are conducting a head-to-head, prospective, double-blind comparison of C2 and C0 monitoring in this group of patients. Anamarija Jorga Atholl Johnston David W. Holt