Predicting Individual Changes in Terminal Half-Life After Switching to Extended Half-Life Concentrates in Patients With Severe Hemophilia
Versloot, Olav; Iserman, Emma; Chelle, Pierre; Germini, Federico; Edginton, Andrea N; Schutgens, Roger E G; Iorio, Alfonso; Fischer, Kathelijn
(2022) HemaSphere, volume 6, issue 4, pp. 1 - 7
(Article)
Abstract
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
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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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Keywords: Hematology, Journal Article
ISSN: 2572-9241
Publisher: Wolters Kluwer Health
Note: Funding Information: The Van Creveldkliniek has received speaker fees from Novo Nordisk and research support from Bayer for work done by OV. FG has received research funds from Novo Nordisk, Roche, Takeda, Bayer. AE has received speaker’s fees from Bayer and Pfizer and research funds via the University of Waterloo from Grifols, Novo Nordisk and Bayer. RS has received research support from CSL-Behring and Sanquin, and is an editor for HemaSphere. AI receives career support via the Mike Gent Chair in HealthCare Research. He has received research funds via McMaster from Bayer, BioMarin, CSL, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Spark, Takeda, and Uniqure. The Van Creveldkliniek has received speaker’s fees from Bayer, Baxter/Shire, Biotest, CSL-Behring, Octapharma, Pfizer, Novo Nordisk; consultancy fees from Baxter/Shire, Biogen, CSL-Behring, Freeline, NovoNordisk, Pfizer, Roche and SOBI; and research support from Bayer, Pfizer, Baxter/Shire, and Novo Nordisk for work done by KF. All the other authors have no conflicts of interest to disclose. Funding Information: The authors wish to thank the members of the Executive Committee of the International Prophylaxis Study Group (Drs. Lou Aledort, Rolf Ljung, and Victor Blanchette) and of the Pharmacokinetics (PK) Expert Working Group of the International Prophylaxis Study Group (Drs. Massimo Morfini, Guy Young, Victor Blanchette and Savita Rangarajan) for their useful comments regarding this manuscript. Drs. Alfonso Iorio and Kathelijn Fischer are members of the PK Expert Working Group of the IPSG. The IPSG is funded by educational grants to the Hospital for Sick Children (“SickKids”) Foundation from Bayer, Novo Nordisk Health Care AG, Pfizer, Sanofi, Takeda and Spark Therapeutics. The IPSG provided salary support for Olav Versloot, a PhD student working under the supervision of Dr. Kathelijn Fischer at the University Medical Centre Utrecht, the Netherlands, for his work regarding this collaborative project. None of the industry partners of the IPSG were involved with the design or conduct of the work reported in this manuscript and the opinions reported in the manuscript are those of the authors alone on behalf of this IPSG/WAPPS collaboration. Publisher Copyright: © 2022 Wolters Kluwer Health. All rights reserved.
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