Conclusion
The use of biologicals like recombinant therapeutic proteins, monoclonal antibodies, fusion proteins and conjugates is expanding. Many of these can be extended to off-label indications within the field of solid organ transplantation based on available experience from their use on other, labelled indications. However, pharmacokinetic characteristics of these large, partly also immunogenic molecules differ from those of traditional small molecules, and the variability may depend on factors like target mediated elimination which complicates extrapolation from one disease to another. So far the studies that have explored individualization by concentration measurements and modelling have been proof-of-concept or feasibility studies that lack the power to provide evidence for eventual improvement in clinical outcome.
For some drugs like alemtuzumab, eculizumab, rituximab, tocilizumab and belatacept the inter-individual variability in pharmacokinetics has been demonstrated. The option for subcutaneous administration may reinforce the need and the potential for individualization by TDM. A few of the drugs mentioned -probably also for some in the pipeline- there is an economic aspect of appropriate dosing that needs to be pursued. Available assays and models to refine interpretation are in place, the obstacles are in the challenges to perform trials of adequate size to document the usefulness of TDM and model informed precision dosing.