Model informed precision dosing
If the criteria for TDM are met, the application in the clinical setting can be improved by the use of population PK/PD models to facilitate model informed precision dosing (MIPD). Such models have been developed, validated and applied in research for decades -for small molecule drugs and increasingly also for biologicals. However, the implementation of such tools into the clinical use of biologicals has been limited, which may also reflect the sparse evidence for the role of TDM in this setting. There are examples especially in the therapy of inflammatory bowel disease and some other immune diseases where MIPD has been explored to guide personalization [20-23]. Also for a drug like alemtuzumab a PK/PD model was developed for patients treated for chronic lymphocytic leukaemia (CLL) [24]. Although the model performed well in this setting, the study highlighted the nonlinear and time-dependent pharmacokinetics due to changes in WBC count for the CLL patients, which again illustrates that models may not be applied in other patient populations like transplanted patients. A lot of work has been invested to better understand the contributions of physiological processes and drug characteristics that govern the PK and PD and hence can guide the model development. The more complex descriptions may be more relevant in the process of mAbs development [19, 25], however there may also be lessons to learn for models. How the application of a PK/PD model can improve the personalization of a biologic like eculizumab, has been elegantly demonstrated by the work of a group at Cincinnati Children’s Hospital. The treatment of transplant-associated thrombotic microangiopathy (TA-TMA) in children and young adults undergoing hematopoietic stem cell transplantation (HSCT) was prospectively individualized by support of a model that was proven effective for eculizumab versus outcome of these severe adverse effects of the HSCT [26, 27].