Biologics in Kidney Transplantation: Why and How Should We Personalize Their Dosage?

The therapeutic arsenal of immunosuppressive drugs in kidney transplantation has recently expanded with the introduction of biologics, approved or used off-label, that specifically target the immune system. Although therapeutic drug monitoring is well established for calcineurin inhibitors, its utility for biological immunosuppressants remains unclear. The objective of this narrative review was to evaluate whether biologics used to prevent or treat renal allograft rejection could be suitable candidates for therapeutic drug monitoring. This review provides (1) a comprehensive and up-to-date synthesis on the pharmacological targets of biologics used in kidney transplantation, (2) assesses the interindividual variability of the pharmacokinetics and pharmacokinetic/pharmacodynamic relationships of key biologics, including belatacept, tocilizumab, rituximab, basiliximab, alemtuzumab, eculizumab, ravulizumab, daratumumab, and imlifidase and (3) describes the analytical methods available for their quantification. This review underscores that, although none of these biologics currently meet all criteria for routine therapeutic drug monitoring, emerging clinical evidence indicates that individualized dosing could enhance both therapeutic outcomes and cost effectiveness. It also discusses future directions for improving pharmacokinetic/pharmacodynamic knowledge on biological therapies in kidney transplant recipients and places in perspective the potential of therapeutic drug monitoring to improve the benefit-risk ratio and cost effectiveness of these biologics.