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

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 ac...

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Autores principales: Goedhart, Tine M.H.J., Bukkems, Laura H., van Moort, Iris, Spence, Colin C., Zwaan, Michel C., de Maat, Moniek P.M., Mathôt, Ron A.A., Cnossen, Marjon H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546314/
https://www.ncbi.nlm.nih.gov/pubmed/35526235
http://dx.doi.org/10.1111/hae.14575
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author Goedhart, Tine M.H.J.
Bukkems, Laura H.
van Moort, Iris
Spence, Colin C.
Zwaan, Michel C.
de Maat, Moniek P.M.
Mathôt, Ron A.A.
Cnossen, Marjon H.
author_facet Goedhart, Tine M.H.J.
Bukkems, Laura H.
van Moort, Iris
Spence, Colin C.
Zwaan, Michel C.
de Maat, Moniek P.M.
Mathôt, Ron A.A.
Cnossen, Marjon H.
author_sort Goedhart, Tine M.H.J.
collection PubMed
description 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 concentration‐time 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.
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spelling pubmed-95463142022-10-14 Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic‐guided dosing of replacement therapy in haemophilia A? Goedhart, Tine M.H.J. Bukkems, Laura H. van Moort, Iris Spence, Colin C. Zwaan, Michel C. de Maat, Moniek P.M. Mathôt, Ron A.A. Cnossen, Marjon H. Haemophilia Original Articles 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 concentration‐time 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. John Wiley and Sons Inc. 2022-05-08 2022-07 /pmc/articles/PMC9546314/ /pubmed/35526235 http://dx.doi.org/10.1111/hae.14575 Text en © 2022 The Authors. Haemophilia published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Goedhart, Tine M.H.J.
Bukkems, Laura H.
van Moort, Iris
Spence, Colin C.
Zwaan, Michel C.
de Maat, Moniek P.M.
Mathôt, Ron A.A.
Cnossen, Marjon H.
Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic‐guided dosing of replacement therapy in haemophilia A?
title Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic‐guided dosing of replacement therapy in haemophilia A?
title_full Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic‐guided dosing of replacement therapy in haemophilia A?
title_fullStr Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic‐guided dosing of replacement therapy in haemophilia A?
title_full_unstemmed Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic‐guided dosing of replacement therapy in haemophilia A?
title_short Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic‐guided dosing of replacement therapy in haemophilia A?
title_sort does difference between label and actual potency of factor viii concentrate affect pharmacokinetic‐guided dosing of replacement therapy in haemophilia a?
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546314/
https://www.ncbi.nlm.nih.gov/pubmed/35526235
http://dx.doi.org/10.1111/hae.14575
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