A5067266121- Hemophilia Treatment and Research
- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Blood groups and transfusion
- Heparin-Induced Thrombocytopenia and Thrombosis
- Microscopic Colitis
- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- Inflammatory Bowel Disease
- Pneumonia and Respiratory Infections
- Antibiotics Pharmacokinetics and Efficacy
- Biosimilars and Bioanalytical Methods
- Hemostasis and retained surgical items
- Acute Myocardial Infarction Research
- Pharmacological Effects and Toxicity Studies
- Statistical Methods in Clinical Trials
- Cardiac Imaging and Diagnostics
- HIV/AIDS drug development and treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Autoimmune and Inflammatory Disorders
- Cardiovascular Function and Risk Factors
- Blood disorders and treatments
- Gastrointestinal Bleeding Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
Amsterdam University Medical Centers
2019-2024
University of Amsterdam
2019-2024
Amsterdam UMC Location University of Amsterdam
2018
Summary Background Infliximab is a chimeric monoclonal antibody against tumour necrosis factor‐alpha for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Recently, subcutaneous formulation CT‐P13, an infliximab biosimilar, was approved clinical use. Aims To characterise CT‐P13 pharmacokinetics (PK) its clinically relevant determinants after administration through population PK modelling. Methods Data from two‐part Phase I study with intravenous (5 mg/kg) variable...
Clinical severity of hemophilia A (HA) varies, possibly due to interplay many factors in the hemostatic pathway. Pharmacokinetic monitoring factor VIII (FVIII) replacement therapy HA patients consists measuring FVIII activity levels and subsequent dose adjustment. The Nijmegen Hemostasis Assay (NHA) measures thrombin generation (TG) plasmin (PG).To determine differences TG PG between before during a pharmacokinetic study identify best parameters develop pharmacodynamic model.Twenty-five...
Background Little is known on how sports participation affects bleeding risk in hemophilia. This study aimed to examine associations between participation, factor VIII (FVIII) levels and persons with hemophilia A. Methods In this observational, prospective, single-center study, A who regularly participated were followed for 12 months. The of patient characteristics, FVIII levels, type/frequency analyzed by repeated time-to-event modelling. Results One hundred twelve (median age: 24 years...
The currently published population pharmacokinetic (PK) models used for PK-guided dosing in hemophilia patients are based on clinical trial data and usually not externally validated practice. aim of this study was to validate a model recombinant factor VIII-Fc fusion protein (rFVIII-Fc) concentrate develop an enriched using independently collected if required. Clinical from A treated with rFVIII-Fc (Elocta) participating the United Kingdom Extended Half-Life Outcomes Registry were collected....
When emicizumab is dosed according to label, clinicians are obligated discard or overdose medication due discrepancies between calculated dose and vial content. The aim of this study was compose a cost-efficient maintenance dosing regimen using Monte Carlo simulation based on size, patient-friendly intervals, patient characteristics, while striving for similar plasma concentrations as observed in clinical trials.Monte simulations were used investigate alternative regimens patients weighing 3...
Abstract Background von Willebrand factor (VWF) is crucial for optimal dosing of VIII (FVIII) concentrate in hemophilia A patients as it protects FVIII from premature clearance. To date, unknown how VWF behaves and what its impact on clearance the perioperative setting. Aim investigate kinetics (VWF antigen [VWF:Ag]), glycoprotein Ib binding (VWF:GPIbM), propeptide (VWFpp) severe moderate included randomized controlled OPTI-CLOT trial. Methods Linear mixed effects modeling was applied to...
Prophylactic treatment of haemophilia A patients with factor VIII (FVIII) concentrate focuses on maintaining a minimal trough FVIII activity level to prevent bleeding. However, due differences in bleeding tendency, the pharmacokinetic (PK)-guided dosing approach may be suboptimal. An alternative could addition haemostatic pharmacodynamic (PD) parameters, reflecting patient's unique balance. Our aim was develop population PK/PD model, based levels and Nijmegen Haemostasis Assay (NHA)...
Abstract Recent studies have reported that patients with von Willebrand disease treated perioperatively a factor (VWF)/factor VIII (FVIII) concentrate ratio of 2.4:1 (Humate P/Haemate P) often present VWF and/or FVIII levels outside prespecified target necessary to prevent bleeding. Pharmacokinetic (PK)-guided dosing may resolve this problem. As clinical guidelines increasingly recommend aiming for certain both and FVIII, application an integrated population PK model describing activity...
Abstract Publications on the exposure‐effect relationships of factor concentrates for hemophilia treatment are limited, whereas such analyses give insight efficacy. Our objective was to examine relationship between dose, VIII (FVIII) levels and bleeding rFVIII‐SingleChain (lonoctocog alfa, Afstyla). Data from persons with severe A prophylaxis three clinical trials were combined. The published population pharmacokinetic (PK) model evaluated expanded. probability described a parametric...
Many patients with von Willebrand disease (VWD) are treated on demand factor and VIII (FVIII) containing concentrates present VWF and/or FVIII plasma levels outside set target levels. This carries a risk for bleeding potentially thrombosis. Development of population pharmacokinetic (PK) model based is first step to more accurate on-demand perioperative dosing this concentrate.Patients VWD undergoing surgery in Academic Haemophilia Treatment Centers the Netherlands between 2000 2018 FVIII/VWF...
Abstract Background The pharmacokinetic (PK) properties of extended half-life (EHL) factor VIII (FVIII) concentrates differ, leading to variation in the optimal dosing regimen for individual patient. aim this study was establish these PK differences various EHL FVIII by silico simulations. Methods level over time profiles rFVIII-SC, BAY 81–8973, rFVIII-Fc, BAX 855, 94–9027, and standard (SHL) rFVIII were simulated 1,000 severe hemophilia A patients during steady-state 40 IU/kg every 72 hours...
Pharmacokinetic (PK) differences between the extended half-life (EHL) factor IX (FIX) concentrates for hemophilia B exist, which may influence hemostatic efficacy of replacement therapy in patients. Therefore, we aimed to evaluate PK properties three EHL-FIX and compare them a standard (SHL) recombinant FIX (rFIX) concentrate.Activity-time profiles PEGylated (N9-GP), linked with human albumin (rIX-FP), coupled IgG1 Fc-domain (rFIXFc), SHL rFIX were simulated 10,000 patients during...
Recombinant factor IX Fc fusion protein (rFIX-Fc) is an extended half-life concentrate administered to haemophilia B patients. So far, a population pharmacokinetic (PK) model has only been published for patients aged ≥12 years. The aim was externally evaluate the predictive performance of rFIX-Fc PK all ages and develop that describes using real-world data.
In resource-rich countries, almost all severe hemophilia patients receive prophylactic replacement therapy with factor concentrates to prevent spontaneous bleeding in joints and muscles decrease the development of arthropathy risk long-term disability. Pharmacokinetic (PK)-guided dosing can be applied individualize therapy, as interindividual differences PK parameters influence VIII (FVIII) FIX activity levels. PK-guided may therefore lead more optimal safeguarding FVIII/FIX levels during...
To account for interindividual variability in the pharmacokinetics (PK) of factor concentrates, PK-guided dosing is increasingly implemented haemophilia patients. Calculations are based on provided label potency, but legislation allows a potency difference ±20% between and actual potency. It unknown if these differences affect PK guidance.Explore effects individual VIII (FVIII) parameters prediction FVIII trough levels regimens.We analyzed preoperative profiling data from severe moderate A...
Individuals with von Willebrand disease (VWD) require desmopressin testing because of interindividual response differences. However, is burdensome, while not all patients may need extensive testing.
Pharmacokinetic (PK)-guided dosing is used to individualize factor (F)VIII and FIX replacement therapy.
Abstract This work focusses on extending the deep compartment model (DCM) framework to estimation of mixed-effects. By introducing random effects, predictions can be personalized based drug measurements, enabling testing different treatment schedules an individual basis. The performance classical first-order (FO and FOCE) machine learning variational inference (VI) algorithms were compared in a simulation study. In VI, posterior distributions variables are approximated using whose parameters...
Abstract Introduction Haemophilia A patients require perioperative clotting factor replacement to limit excessive bleeding. Weight‐based dosing of Factor VIII (FVIII) does not account for inter‐individual pharmacokinetic (PK) variability, and may lead suboptimal FVIII exposure. Aim To perform an external validation a previously developed population PK (popPK) model in haemophilia patients. Methods retrospective chart review identified at the University North Carolina (UNC) between April 2014...
Von Willebrand disease (VWD) is a bleeding disorder, caused by deficiency or defect of von factor (VWF). In case medical procedures bleeding, patients are treated with desmopressin and/or VWF-containing concentrates to increase plasma VWF and VIII (FVIII). However, in many cases these levels outside the targeted range. Therefore, population pharmacokinetic (PK) models have been developed, which aim quantify explain intraindividual interindividual differences treatment response. These enable...