A comparison of methods for prediction of pharmacokinetics when switching to extended half-life products in hemophilia A patients

Yu, Jacky K.; Iorio, Alfonso; Edginton, Andrea N.

doi:10.1016/j.thromres.2020.10.024

Cited by 2 publications

(5 citation statements)

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“…The accuracy of the modeled data is associated with the number of samples taken for PK assessment. 41 , 42 Estimates based on only 1 sample may cause bias. However, a sensitivity analysis suggests no significant effect of adding “number of samples” to the model.…”

Section: Discussionmentioning

confidence: 99%

“…Still, future studies should aim to exclusively include patients with multiple assessments to model more accurate data and to avoid inaccurate estimation of true THL. 42 …”

Section: Discussionmentioning

confidence: 99%

“…The accuracy of the modeled data is associated with the number of samples taken for PK assessment 41,42 . Estimates based on only 1 sample may cause bias.…”

Section: Discussionmentioning

confidence: 99%

“…However, a sensitivity analysis suggests no significant effect of adding “number of samples” to the model. Still, future studies should aim to exclusively include patients with multiple assessments to model more accurate data and to avoid inaccurate estimation of true THL 42 …”

Section: Discussionmentioning

confidence: 99%

“…Still, future studies should aim to exclusively include patients with multiple assessments to model more accurate data and to avoid inaccurate estimation of true THL. 42 THL is known to be lower in blood group O than in non-O for patients with hemophilia A. 26,43 However, this does not directly explain why blood group non-O is a relevant predictor of a higher increase in THL.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

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Predicting Individual Changes in Terminal Half-Life After Switching to Extended Half-Life Concentrates in Patients With Severe Hemophilia

et al. 2022

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Predicting individual effects of switching from standard half-life (SHL) to extended half-life (EHL) FVIII/FIX concentrates is pivotal in clinical care, but large-scale individual data are scarce. The aim of this study was to assess individual changes in terminal half-life (THL) after switching to EHL concentrates and identifying determinants of a clinically relevant THL extension in people with severe hemophilia. Data from participants with pharmacokinetic studies on both SHL and EHL were extracted from the Web-Accessible Population Pharmacokinetics Service (WAPPS) database and stratified according to hemophilia type and age groups (children/adults). A 30% increase in THL was considered clinically relevant. Predictors of a relevant increase were identified using logistic regression. Data from 688 persons with severe hemophilia (2174 infusions) were included: 89% hemophilia A; median age: 21.7 (interquartile range [IQR]: 11.5–37.7); positive inhibitor history: 11.7%. THL increased by 38% (IQR: 17%–67%) and 212% (139%–367%) for hemophilia A and B, respectively. All EHL-FIX concentrate users showed clinically relevant THL extension. However, 40% (242/612) of people with hemophilia A showed limited extension or decrease in THL after switching. Relevant FVIII-THL extension was predicted by short baseline THL and blood group non-O in both children and adults. In conclusion, clinically relevant THL extension was observed in all 75/76 participants switching to EHL-FIX, and in 60% of 612 switching to EHL-FVIII. Short THL on SHL-FVIII and blood group non-O were identified as predictors for a relevant THL increase after switching to EHL-FVIII. Individualized pharmacokinetic assessment may guide clinical decision-making when switching from SHL to EHL-FVIII.

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Section: Discussionmentioning

confidence: 99%

“…Still, future studies should aim to exclusively include patients with multiple assessments to model more accurate data and to avoid inaccurate estimation of true THL. 42 …”

Section: Discussionmentioning

confidence: 99%

“…The accuracy of the modeled data is associated with the number of samples taken for PK assessment 41,42 . Estimates based on only 1 sample may cause bias.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Strengths and Limitationsmentioning

confidence: 99%

See 3 more Smart Citations