Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic‐guided dosing of replacement therapy in haemophilia A?

Abstract

Background: To account for interindividual variability in the pharmacokinetics (PK) of factor concentrates, PK-guided dosing is increasingly implemented in haemophilia patients. Calculations are based on provided label potency, but legislation allows a potency difference of ±20% between label and actual potency. It is unknown if these differences affect PK guidance.Aim: Explore the effects of potency differences on individual factor VIII (FVIII) PK parameters and the prediction of FVIII trough levels of dosing regimens. Methods:We analyzed individual preoperative PK profiling data from severe and moderate haemophilia A patients included in the OPTI-CLOT randomized controlled trial.Label and actual potency were compared, with data on potency provided by pharmaceutical companies. For both potencies, individual PK parameters were estimated and concentration-time curves were constructed by nonlinear mixed-effects modelling. Finally, we explored the effect of both the identified and the maximum legislated potency difference on predicted FVIII trough levels infused in a low and high dose regimen. Results:In 45/50 included patients, actual potency was higher than its label potency.The median potency difference was 6.0% (range -9.2% to 18.4%) and resulted in varying individual PK parameter estimates but practically identical FVIII concentrationtime curves. As expected, predicted FVIII trough levels were linearly correlated to the actual dose. Conclusion:It is not necessary to take potency differences into account when applying PK guidance of FVIII concentrates in haemophilia A patients. However, when the patient is switched to another FVIII batch after PK-guided dosing, trough levels may deviate ±20% from calculations based on label dose.