TDM of belatacept and other biologicals in transplantation.

Abstract

In solid organ transplantation biologicals like recombinant therapeutic proteins, monoclonal antibodies, fusion proteins and conjugates are increasingly used for immunosuppression, desensitization, ABO incompatibility, antibody mediated rejections and atypical hemolytic uremic syndrome. For some of these drugs this represents off-label use; and the evidence to define their role in current therapies and the evidence for their clinical benefit may be sparse. Biologicals are large molecules compared to traditional drugs, and the processes that define their pharmacokinetics are different. Validated drug assays that can be applied in clinical routine are to a large extent available. Dosing is currently mostly standard -either fixed doses or adjusted according to body size; and when drug concentrations have been measured, large variability in distribution and elimination has been demonstrated. This opens for the proposal to identify optimal concentration ranges, establish PK/PD models for interpretation and guidance, leading to model informed precision dosing. Extrapolation of the results from use of these drugs on other indications may provide some of the necessary information. For drugs like alemtuzumab, eculizumab, rituximab, tocilizumab and belatacept there may be a potential for model informed precision dosing. However, for all of these the challenge is to perform studies that are properly designed to provide evidence for beneficial outcome related to the individualization of treatment. This calls for collaboration within the transplantation and TDM community.