Individualizing liver transplant immunosuppression using a phenotypic personalized medicine platform.
Zarrinpar A, Lee DH, et al.Science Translational Medicine 2016; 8(333): 333ra349.
Aims
To evaluate the effectiveness of a phenotypic personalized medicine (PPM) approach toward optimized tacrolimus dosing, compared to conventional physician guided dosing in liver transplant recipients.
Interventions
Participants were randomized to receive either parabolic personalized dosing (PPD) assisted immunosuppression dosing, or standard-of-care immunosuppression dosing.
Participants
8 liver transplant recipients.
Outcomes
The primary outcome measured was tacrolimus trough levels. Other outcomes measured were extended hospital stays, substantial deviations from the target range, total treatment period, number of days in the hospital, and inter and intra-patient variance.
Follow-up
Until hospital discharge
CET Conclusions
This interesting study uses a computation approach, called “parabolic personalised dosing†(PPD) to adjust tacrolimus dosing in inpatients following liver transplant. PPD takes an input (the tacrolimus dose) and predicts the phenotypic output (the trough tacrolimus level) based upon a second-order polynomial equation. This equation is specific to an individual patient, calculated from prior trough levels and dose responses. When a patients’ condition or management changes (for example addition of antibiotics, haemodialysis) the personalised equation is “recalibrated†to adjust the prediction. The model derived is able to recommend an appropriate dose of tacrolimus for an individual patient. This study compares 4 patients managed using PPD with 4 control patients managed by normal physician-led dosing. Clearly these numbers are too small to make any meaningful conclusions regarding efficacy, although the authors do report reduced intra-individual variation with PPD. The approach is interesting, and addresses a significant weakness in our current management of immunosuppression. Larger scale comparative trials will be required to assess whether PPD demonstrates clinical benefit in terms of improved dosing and clinical outcomes. Another consideration with any dose suggestion model is clinician compliance – previous studies of MMF monitoring have suggested that clinicians do not always follow computer recommendations in the real-world setting!
Data analysis
Per protocol analysis
Trial registration
None