In silico evaluation of limited blood sampling strategies for individualized recombinant factor IX prophylaxis in hemophilia B patients

Preijers, Tim; Hazendonk, H. C. A. M.; Fijnvandraat, Karin; Leebeek, Frank W.G.; Cnossen, Marjon H.; Mathôt, R. A. A.

doi:10.1111/jth.13771

Cited by 13 publications

(12 citation statements)

References 40 publications

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“…Consequently, the better the PK profiles and covariate relationships are described, the more reliable Bayesian forecasting will be. This approach is increasingly used in PK tailoring [13–16] and has been shown to be reliable in a limited sampling environment [16–19].…”

Section: Introductionmentioning

confidence: 99%

Routine clinical care data for population pharmacokinetic modeling: the case for Fanhdi/Alphanate in hemophilia A patients

Chelle

Yeung

Bonanad

et al. 2019

J Pharmacokinet Pharmacodyn

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Fanhdi/Alphanate is a plasma derived factor VIII concentrate used for treating hemophilia A, for which there has not been any dedicated model describing its pharmacokinetics (PK). A population PK model was developed using data extracted from the Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) project. WAPPS-Hemo provided individual PK profiles for hemophilia patients using sparse observations as provided in routine clinical care by hemophilia centers. Plasma factor activity measurements and covariate data from hemophilia A patients on Fanhdi/Alphanate were extracted from the WAPPS-Hemo database. A population PK model was developed using NONMEM and evaluated for suitability for Bayesian forecasting using prediction-corrected visual predictive check (pcVPC), cross validation, limited sampling analysis and external evaluation against a population PK model developed on rich sampling data. Plasma factor activity measurements from 92 patients from 12 centers were used to derive the model. The PK was best described by a 2-compartment model including between subject variability on clearance and central volume, fat free mass as a covariate on clearance, central and peripheral volumes, and age as covariate on clearance. Evaluations showed that the developed population PK model could predict the PK parameters of new individuals based on limited sampling analysis and cross and external evaluations with acceptable precision and bias. This study shows the feasibility of using real-world data for the development of a population PK model. Evaluation and comparison of the model for Bayesian forecasting resulted in similar results as a model developed using rich sampling data.Electronic supplementary materialThe online version of this article (10.1007/s10928-019-09637-4) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Routine clinical care data for population pharmacokinetic modeling: the case for Fanhdi/Alphanate in hemophilia A patients

Chelle

Yeung

Bonanad

et al. 2019

J Pharmacokinet Pharmacodyn

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“…OPTI‐CLOT, or Patient Tailored Pharmacokinetic‐Guided Dosing of Clotting factor concentrate and DDAVP (1,8‐deamino‐ d ‐arginine vasopressin, also known as desmopressin) in bleeding disorders, is a multicenter Dutch and UK collaboration to implement PK‐guided dosing by construction and validation of perioperative and prophylactic popPK models and incorporating cost‐effectiveness assessment. Data collection has enabled the development of popPK models for use in perioperative dosing in hemophilia , which will be tested in a randomized controlled trial . PopPK models are also being constructed for prophylaxis with SHL, EHL and DDAVP in hemophilia and von Willebrand disease .…”

Section: Pharmacokinetic Modelsmentioning

confidence: 99%

Pharmacokinetics and the transition to extended half‐life factor concentrates: communication from the SSC of the ISTH

Ragni

Croteau

Morfini

et al. 2018

Journal of Thrombosis and Haemostasis

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Extended half-life proteins (EHL) are increasingly used in clinical practice, but there is no standardized approach to sampling, interpretation and implementation of pharmacokinetics (PK) data to maximize treatment benefit. The goal of EHL treatment is to attain a trough level sufficient to protect against spontaneous bleeds and reduce infusion frequency and limitations on individual activity and lifestyle. Performing classical PK assessments requires multiple blood samples, which is burdensome for patients and providers. Herein we review a population pharmacokinetic (popPK) approach to estimate individual PK parameters to transition patients from standard half-life (SHL) to EHL concentrates. We propose that a minimum of two to four post-infusion samples is sufficient to estimate individual PK profiles, with sufficient certainty to maintain factor levels above 1% and achieve bleed-free lifestyles. We also survey current PK use in patients transitioning to EHL, review key PK parameters and popPK models, and recommend an approach to using PK in patients initiating or switching to EHL.

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“…In addition, population PK models allow optimization of clotting factor dosing by an in silico evaluation. In the latter, Monte Carlo simulations are applied that allow the exploration of the resulting factor levels as the dosing regimen or patient characteristics varied [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetics of Clotting Factor Concentrates and Desmopressin in Hemophilia

et al. 2020

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Hemophilia A and B are bleeding disorders caused by a deficiency of clotting factor VIII and IX, respectively. Patients with severe hemophilia (< 0.01 IU mL −1) and some patients with moderate hemophilia (0.01-0.05 IU mL −1) administer clotting factor concentrates prophylactically. Desmopressin (d-amino d-arginine vasopressin) can be applied in patients with nonsevere hemophilia A. The aim of administration of factor concentrates or desmopressin is the prevention or cessation of bleeding. Despite weight-based dosing, it has been demonstrated that factor concentrates still exhibit considerable pharmacokinetic variability. Population pharmacokinetic analyses, in which this variability is quantified and explained, are increasingly performed in hemophilia research. These analyses can assist in the identification of important patient characteristics and can be applied to perform patient-tailored dosing. This review aims to present and discuss the population pharmacokinetic analyses that have been conducted to develop population pharmacokinetic models describing factor levels after administration of factor VIII or factor IX concentrates or d-amino d-arginine vasopressin. In total, 33 publications were retrieved from the literature. Two approaches were applied to perform population pharmacokinetic analyses, the standard two-stage approach and non-linear mixed-effect modeling. Using the standard two-stage approach, four population pharmacokinetic models were established describing factor VIII levels. In the remaining 29 analyses, the non-linear mixed-effect modeling approach was applied. NONMEM was the preferred software to establish population pharmacokinetic models. In total, 18 population pharmacokinetic analyses were conducted on the basis of data from a single product. From all available population pharmacokinetic analyses, 27 studies also included data from pediatric patients. In the majority of the population pharmacokinetic models, the population pharmacokinetic parameters were allometrically scaled using actual body weight. In this review, the available methods used for constructing the models, key features of these models, patient population characteristics, and established covariate relationships are described in detail.

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In silico evaluation of limited blood sampling strategies for individualized recombinant factor IX prophylaxis in hemophilia B patients

Cited by 13 publications

References 40 publications

Routine clinical care data for population pharmacokinetic modeling: the case for Fanhdi/Alphanate in hemophilia A patients

Routine clinical care data for population pharmacokinetic modeling: the case for Fanhdi/Alphanate in hemophilia A patients

Pharmacokinetics and the transition to extended half‐life factor concentrates: communication from the SSC of the ISTH

Population Pharmacokinetics of Clotting Factor Concentrates and Desmopressin in Hemophilia

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