Abstract Number: PB0938
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Inter-individual differences in pharmacokinetic (PK) response influence coagulation factor VIII (FVIII) activity levels in hemophilia A patients and should be accounted for. Dosing can be individualized by PK-guidance of treatment. To date, it is unknown if factor concentrate vial variation between label and actual potency, as allowed by legislation, impacts individual PK parameters and therefore predicted FVIII activity levels.
Aims: Explore effects of vial variation between label and actual potency to determine if FVIII antigen/activity (Ag/Act) ratio influences analyses of individual FVIII PK parameters and therefore predicted FVIII activity levels.
Methods: We analyzed data of severe and moderate hemophilia A patients from the OPTI-CLOT randomized controlled perioperative trial. FVIII vial label potency was documented. Actual FVIII potency of used vials during preoperative individual PK profiling were provided by pharmaceutical companies. Paired t-testing was performed to analyze differences between PK parameters estimated by Bayesian estimation using nonlinear mixed-effects modelling (NONMEM) using both label and actual potency. Multiple regression was applied to evaluate independent effects of variation in potencies on differences in estimated clearance.
Results: Fifty patients with median age of 47.5 years (range 4.0-76.9) were included. Mean variation between label and actual potency was 6.8% (range 0.0-15.5%). Actual potency was higher in 45 patients (mean difference 323 IU, standard deviation 33 IU), leading to significant differences between PK parameters (p< 0.001; Figure 1). Difference in clearance was predicted by potency variation for 80%, independent of PK modifying factors age, blood group O and VWF:act (p< 0.001). However, altered PK parameters do not affect FVIII concentration-time curves of patients' PK profiles (Figure 2).
Conclusions: In conclusion, the observed higher actual potency than label potency of FVIII concentrate vials leads to alterations of PK parameters. However, this does not affect FVIII activity-time profile and does not seem to influence PK-guided FVIII dosing advice.
[Figure 1. Comparison of clearance and steady state volume of distribution estimated using both label and actual potency.***P-value<0.001]
[Figure 2. FVIII activity-time curves of PK profiles using both label (red) and actual potency (blue). PK profiles overlap for all patients.]
To cite this abstract in AMA style:
Goedhart MHJ, Bukkems LH, van Moort I, Spence CC, Gouw SC, Mathôt RAA, Cnossen MH, for the OPTI-CLOT Study Group . Does Variation between Label and Actual Potency of Factor VIII Concentrate Vials Affect Results of Pharmacokinetic (PK)-Guided Dosing of Replacement Therapy in Hemophilia A? [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/does-variation-between-label-and-actual-potency-of-factor-viii-concentrate-vials-affect-results-of-pharmacokinetic-pk-guided-dosing-of-replacement-therapy-in-hemophilia-a/. Accessed September 22, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/does-variation-between-label-and-actual-potency-of-factor-viii-concentrate-vials-affect-results-of-pharmacokinetic-pk-guided-dosing-of-replacement-therapy-in-hemophilia-a/