Variability
Based on available reports from the early belatacept trials (see refs in [28]), we concluded in a previous review that the variability in belatacept concentrations seemed to be low -in itself an argument against the need of TDM for this drug [28]. The quoted papers mostly reported geometric means and coefficients of variation of the concentrations and the pharmacokinetic parameters from the applied PK-modelling. However, to get insight into the variability in belatacept PK between individuals, one may re-examine the actual observed individual concentrations in the period (32-52 weeks after first dose) when dosing was similar in the two arms LI (’less intensive’) and MI (’more intensive’). Here trough concentrations ranged from less than 0.1 to around 20 µg/L, and although the authors concluded that’model-predicted time-varying distributions of trough concentrations were in excellent agreement with observed values … and interindividual variability in PK was low, illustrating that belatacept exposure is predictable and suggesting that the need for therapeutic drug monitoring of belatacept may not be needed for KTRs ’, one could still argue that the interindividual variability on this dosing was quite large when compared to therapeutic ranges for other narrow index drugs that are monitored in transplantation. In a couple of later publications similar ranges of observed belatacept concentrations has been reported as part of the validation of new assays for belatacept concentrations [4, 7]. The patients in both of these reports, n=5 [4] and n=108 [7] were followed in the stable phase of belatacept maintenance following switch from tacrolimus.