Large-Scale Real-World Monitoring of Mycophenolic Acid Exposure in Liver Transplantation: Impact of Bayesian Dose...

Mycophenolate mofetil is widely used in liver transplantation but poses dosing challenges owing to the narrow therapeutic window and high pharmacokinetic variability of its active moiety, mycophenolic acid (MPA). Overexposure increases the risk of adverse effects, whereas underexposure increases the risk of rejection and graft loss. The ImmunoSuppressant Bayesian Dose Adjustment (ISBA) platform estimates the MPA area under the curve (AUC) 0-12h using 3 post-dose samples (20 minutes, 1 hour, 3 hours) and provides dose recommendations to target an AUC 0-12h of 30-60 mg·h/L. The aim of this study was to describe the MPA AUC 0-12h and assess the impact of ISBA-guided dose adjustments.

MPA concentrations were measured at each visit, and AUCs were estimated in real time during routine clinical follow-up. All data collected from liver-transplant recipients aged ≥18 years from October 2005 to May 2020 were retrospectively analyzed. Dosing recommendations were adjusted proportionally to reach the AUC target of 45 mg.h/L.

A total of 3632 requests involving 1872 patients were analyzed, making this the largest real-world cohort of this population reported to date. Among them, 658 patients benefited from at least 2 successive dose adjustments, allowing for a comparison between the results obtained without any prior use of the online platform and those obtained after the first visit (AUC of the second visit). At the first visit (before any dose recommendation) during the first year after transplantation, the median AUC 0-12h (interquartile range) was 27 (16-39) mg·h/L (n = 422). After dose adjustment recommendation, the median AUC 0-12h increased significantly to 38 (30-49) mg·h/L (n = 205, P < 0.001). The proportion of patients within the therapeutic target range (30-60 mg.h/L) increased from 40% to 61% (+21%, P < 0.001).

Many patients were underexposed to MPA before dose adjustment. The ISBA recommendations significantly improved target attainment rates.