Predictive performance of a Bayesian forecasting software for tacrolimus in adult heart transplant

Introduction: Previous clinical audit of tacrolimus (TAC) in 2017 heart transplant (HTx) recipients at St Vincent’s Hospital, Sydney (SVH) observed poor sampling time of TAC trough concentrations.Bayesian forecasting software may assist in the interpretation of TAC concentrations collected at any point in time.

Aims: To evaluate the predictive performance of a Bayesian forecasting software, DoseMeRx® (Brisbane, Australia) in predicting oral immediate-release TAC concentrations immediately post-HTx at SVH.

Methods: A retrospective observational study of all HTx recipients (1 Jan – 31 Dec 2017) treated with TAC at SVH was conducted. Data inputted intoDoseMeRx® included TAC concentrationsand dosing regimen, and patient parameters such as age, gender, height, weight, haematocrit and CYP 450 3A5 genotype (if available).The predictive performance of DoseMeRx® was evaluated by comparing the predicted concentrations to the observed concentrations using median prediction error (MPE, a measure of bias) and median absolute prediction error (MAPE, a measure of precision). Clinically acceptable bias was between -15% and 15% while clinically acceptable precision was ≤20%.

Results: There were 38 HTx recipients, 25 (66%) males and a median (range) age of 56 (21-69) years. All patients received itraconazole 200 mg BD as a prophylaxis for invasive fungal infection immediately post-HTx for 6 months. During the first 3 weeks of TAC therapy, 328 blood concentrations were measured with a median (range) of 16 (8 – 27) samples per patient. DoseMeRx® under-predicts TAC concentrations for the first 2 weeks of TAC therapy. The software was robustfrom day 11 of therapy: bias was not significant with clinically acceptable bias. DoseMeRx® displayed clinically acceptable precision from day 9.

Discussion: Preliminary assessment of DoseMeRx®immediately post-HTx highlighted accuracy in predicting TAC concentration from day 11. The improvement in MPE and MAPE over a week aligns thedelay in the attainment of steady-state due to drug-interactions between TAC and itraconazole. Further assessment of the predictive performance of DoseMeRx®upon itraconazole cessation after 6 months of therapy is required.