Exposure to mycophenolic acid better predicts immunosuppressive efficacity than exposure to calcineurin inhibitors in renal transplant patients

Abstract : A time to event model was developed to study predictive factors of immunosuppressive efficacy in renal transplant patients and to investigate longitudinal calcineurin inhibitors (CNIs) and mycophenolic acid (MPA) co-exposures, and patient characteristics as potential covariates. The efficacy endpoint included acute rejection, graft loss and death. Data from 222 patients were analyzed: 23 events were observed in 126 patients receiving cyclosporine against 15 in 96 patients receiving tacrolimus (p=0.61) in the two first years post-transplantation. Each 1mg.h/L increase of MPA AUC was associated with a 4% decreased risk of event (hazard ratio (HR) 95% confidence interval (CI): 0.93-0.99). The onset of cytomegalovirus infection/disease significantly increased this risk (HR=10.9; 95% CI: 6.5-21.7). Within the observed ranges, CNIs exposures were not significantly associated with efficacy (i.e. acute rejection, graft loss and death). This work advocates for the avoidance of unnecessary high CNIs dosing and puts forward new arguments for MPA concentration monitoring.