Researchers from UCLA’s Department of Mechanical and Aerospace Engineering and the Department of Psychology have created a new approach for the precise management of tacrolimus, improving patient outcomes following organ transplants. This method proved successful in a 60 patient clinical trial compared to controls and can be applied to other similar immunosuppressive agents.
BACKGROUND
When undergoing an organ transplant, it is necessary to suppress the patient’s immune response posttransplant; otherwise, the transplanted organ will be rejected and attacked by the immune system leading to significant system-wide complications. Accurate and precise immunosuppression can be tricky. While the exact method may change depending on the solid organ being transplanted, most clinicians rely on a multiple drug approach that bases on a dose titration method to reduce complications. Tacrolimus, one of the most used immunosuppressive agents, can be clinically challenging as far as administration since overdosing increases the risks of neurotoxicity and nephrotoxicity. However, even slight underdosing can lead to underimmunosuppression, thus resulting in a narrow therapeutic window. The usual standard of care for dosing of immunosuppressing agents utilizes whole-blood trough concentrations of the metabolized compound. Further adjustments rely on an educated guess based on multiple factors, which may cause a deviation from the target range. Determination of most of these parameters is mainly dependent on clinical experience and can be inconsistent, leading to a frequently observed deviation between target drug levels and observed.
INNOVATION
UCLA researchers have developed a novel method that allows for more precise control of tacrolimus levels in patients following organ transplant. This method leads to more accurate future predictions of tacrolimus in patient serum, resulting in improved patient safety and reduced organ rejection. This method focuses on treatment efficacy for a given patient and more faithfully relates it to drug dosing through a “phenotypic response surface” methodology. This novel phenotype–dose relationship termed “Phenotypic personalized dosing” (PPD) is a readily applicable second-order function that more proficiently projects the target range of the compound based on a set of coefficients specific to the application. Some of which are patient-specific for improved personalized results.
POTENTIAL APPLICATIONS:
● Personalized treatment for patients undergoing organ transplant
● The method can be applied to other immunosuppressive drugs
ADVANTAGES:
● More accurate prediction of tacrolimus levels in patients
● Reduces the chance of organ rejection
● Reduces the chance of toxicity
● Method implementation is easy
● Allows personalized case-by-case treatment
DEVELOPMENT-TO-DATE: Method has been successfully tested through a 60 patient clinical trial in patients post-liver transplant. This method predicted tacrolimus levels with higher accuracy than the control and resulted in more patients staying within the target range.
RELATED PAPERS:
A. Zarrinpar, D.‐K. Lee, A. Silva, N. Datta, T. Kee, C. Eriksen, K. Weigle, V. Agopian, F. Kaldas, D. Farmer, S. E. Wang, R. Busuttil, C.‐M. Ho, and D. Ho “Individualizing liver transplant immunosuppression using a phenotypic personalized medicine platform”, Sci. Transl. Med. 8, 333ra49 (2016)