Therapeutic Drug Monitoring of Belatacept in Kidney Transplantation.

Belatacept is a novel immunosuppressive drug that inhibits the co-stimulatory signal required for T-cell activation and has been approved for the prevention of acute rejection after kidney transplantation. In this article, the need for and possibility of therapeutic drug monitoring (TDM) of belatacept is reviewed. Clinical studies have defined the upper limit of the therapeutic window, but the lower limit is unknown. The pharmacokinetics and pharmacodynamics of belatacept display only limited interpatient variability but no data are available on the intrapatient variability of these parameters. Several assays to measure serum belatacept concentrations and its in vitro immunologic effects have been developed, but these are not commercially available and require validation. Importantly, pharmacodynamic assays have not been correlated with clinical outcomes (both efficacy and safety) and have only used surrogate laboratory readouts. TDM is likely to become feasible in the near future if these assays are developed further. However, because its pharmacokinetics and pharmacodynamics seem to vary little between individual patients, it may not be necessary to perform TDM for this drug. There could be a role for such an approach if one seeks to lower the belatacept doses further in an attempt to minimize adverse events. A future, prospective concentration-ranging study that defines the lower end of the belatacept therapeutic window should, however, be conducted first to provide the rationale for performing TDM of this novel immunosuppressant.