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Hemophilia A is a bleeding disorder characterized by a deficiency of a coagulation factor VIII and optimally treated using pharmacokinetics (PK)‐guided prophylactic replacement therapy. To decrease patient burden, PK can be estimated from sparse sampling leveraging population PK modeling. However, recommendations for sampling times meant for patients with hemophilia A as a group may not be optimal at the individual level. To evaluate a personalized limited sampling approach (Personalized LSA) that suggests a next sampling time point that would provide a more accurate estimation of terminal half‐life of FVIII concentrates when using a population PK approach. 331 PK studies with rich sampling were extracted from the WAPPS‐Hemo database. Two sampling approaches were evaluated and compared: 974 PK studies consisting of two samples were built from the rich sampling data including one sample selected using the personalized LSA prediction; 974 PK studies consisting of two samples were built from the rich sampling data including one sample selected randomly. Half‐life values were estimated on the sparse data and compared within patients to the estimates obtained on the rich data for assessing the error on half‐life values. Relative errors between estimates from sparse sampling data using personalized LSA and from rich sampling data were always lower than 20% and significantly lower than the comparative approach that used random sampling (median–95th percentile were 3.8%–13.1% vs. 7.0%–23.5%, respectively, p‐value < 10−10). Moreover, less than 4% of the samples suggested by the personalized LSA were below the limit of quantification. Identifying the most informative sampling points for PK assessment using a Personalized LSA approach that accounts for individual differences in PK improves the precision of FVIII terminal half‐life estimates in sparse sampling.

Hemophilia A is a bleeding disorder characterized by a deficiency of a coagulation factor VIII and optimally treated using pharmacokinetics (PK)‐guided prophylactic replacement therapy. To decrease patient burden, PK can be estimated from sparse sampling leveraging population PK modeling. However, recommendations for sampling times meant for patients with hemophilia A as a group may not be optimal at the individual level.

Real‐life data on pharmacokinetics of factor (F) VIII/IX concentrates, especially extended half‐life (EHL), concentrates in large cohorts of persons with hemophilia are currently lacking. This cross‐sectional study aimed to establish reference values for terminal half‐life (THL) for FVIII/IX concentrates according to concentrate type, age, blood group and inhibitor history. Data were extracted from the Web‐Accessible Population Pharmacokinetics Service database. Groups were compared by nonparametric tests. THL was modelled according to patient characteristics and concentrate type. Infusion data (n= 8022) were collected from 4832 subjects (including 2222 children) with severe hemophilia (age: 1 month–85 years; 89% hemophilia A; 34% using EHL concentrates, 9.8% with history of inhibitors). THL of FVIII‐EHL was longer than of FVIII standard half‐life (SHL; median 15.1 vs. 11.1 h). FVIII‐THL was dependent on age, concentrate type, blood group, and inhibitor history. THL of FIX‐EHL was longer than of FIX‐SHL (median 106.9 vs. 36.5 h). FIX‐THL increased with age until 30 years and remained stable thereafter. FVIII‐THL was shorter in subjects with blood group O. THL was decreased by 1.3 h for FVIII and 22 h for FIX in subjects with a positive inhibitor history. We established reference values for FVIII/IX concentrates according to patient characteristics and concentrate type in a large database of hemophilia patients. These reference values may inform clinical practice (e.g., assessment of immune tolerance success), economic implications of procurement processes and value attribution of novel treatments (e.g., mimetics, gene therapy).

Real‐life data on pharmacokinetics of factor (F) VIII/IX concentrates, especially extended half‐life (EHL), concentrates in large cohorts of persons with hemophilia are currently lacking.

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Versloot: Bayer: Research Funding. Germini:Bayer: Research Funding; Roche: Research Funding; Takeda: Research Funding; NovoNordisk: Research Funding. Iorio:CSL: Research Funding; BioMarin: Research Funding; Bayer: Research Funding; Uniqure: Research Funding; Takeda: Research Funding; Spark: Research Funding; Sanofi: Research Funding; Roche: Research Funding; Pfizer: Research Funding; Octapharma: Research Funding; NovoNordisk: Research Funding; Grifols: Research Funding; Freeline: Research Funding. Fischer:Bayer, Biogen, Pfizer, Baxter/Shire, and Novo Nordisk: Research Funding; Bayer, Baxter, Biogen, CSL Behring, Freeline, Novo Nordisk, Pfizer, Roche, and Sobi: Consultancy; Bayer, Baxter/Shire, SOBI/Biogen, CSL Behring, Octapharma, Pfizer, NovoNordisk: Research Funding.

Versloot: Bayer: Research Funding. Germini:Bayer: Research Funding; NovoNordisk: Research Funding; Roche: Research Funding; Takeda: Research Funding. Iorio:Freeline: Research Funding; Pfizer: Research Funding; NovoNordisk: Research Funding; CSL: Research Funding; BioMarin: Research Funding; Octapharma: Research Funding; Takeda: Research Funding; Uniqure: Research Funding; Grifols: Research Funding; Roche: Research Funding; Bayer: Research Funding; Sanofi: Research Funding; Spark: Research Funding. Fischer:Bayer, Biogen, Pfizer, Baxter/Shire, and Novo Nordisk: Research Funding; Bayer, Baxter/Shire, SOBI/Biogen, CSL Behring, Octapharma, Pfizer, NovoNordisk: Research Funding; Bayer, Baxter, Biogen, CSL Behring, Freeline, Novo Nordisk, Pfizer, Roche, and Sobi: Consultancy.

Introduction:Extended half-life concentrates were recently introduced and limited data have shown extended terminal half-life (THL). However, real-life data on pharmacokinetics in large cohorts of patients with haemophilia (PWH) and information on the effects of age, body composition and blood group (THL) are lacking.

Introduction:Extended Half-Life (EHL) concentrates were recently introduced to increase trough levels, decrease infusion frequency and potentially limiting the burden of treatment in patients with haemophilia (PWH) and their caregivers. Group-based studies have reported increased terminal half-life (THL) after switching from standard half-life (SHL) to EHL concentrates. However, available reports have included less than 30 patients and large-scale studies on switching from SHL to EHL concentrates are lacking.

Ozelo: BioMarin: Honoraria, Speakers Bureau; Grifols: Honoraria; Novo Nordisk: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Shire: Honoraria, Research Funding, Speakers Bureau; Bioverativ: Honoraria, Research Funding. Iorio:Shire: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Shire; Pfizer: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Pfizer; NovoNordisk: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Novo Nordisk; Grifols: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Grifols; Octapharma: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Octapharma; CSL: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with CSL; Bayer: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Bayer; Roche: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Roche. Spears:Grifols: Employment. Mir:Grifols: Employment. Edginton:Bayer: Honoraria.

Objective: The Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) platform allows hemophilia treaters to estimate individual PK parameters for clotting factor concentrates using only a few blood samples drawn from their patients. Population pharmacokinetic (PopPK) models used with WAPPS-Hemo are usually built using clinical trial data provided by drug manufacturers. These trials can be restrictive with respect to patient covariates such as age and body weight. On the other hand, real-world pharmacokinetic data submitted to WAPPS captures the breadth of hemophilia patients. We tested the use of post-infusion clotting factor concentrate measurements collected through routine use of WAPPS-Hemo to develop a plasma-derived FVIII (Fanhdi/Alphanate)-specific model for which no trial data was available.