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CC BY-NC-ND 4.0 · Thromb Haemost 2020; 120(02): 277-288
DOI: 10.1055/s-0039-3400745
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

Body Mass Index Best Predicts Recovery of Recombinant Factor VIII in Underweight to Obese Patients with Severe Haemophilia A

Andreas Tiede
1   Hematology, Hemostasis, Oncology and Stem Cell Transplantation Unit, Hannover Medical School, Hannover, Germany
,
Ana Rosa Cid
2   Thrombosis and Haemostasis Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
,
Georg Goldmann
3   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany
,
Victor Jiménez-Yuste
4   Hospital Universitario La Paz, Autónoma University, Madrid, Spain
,
Michael Pluta
5   Quanticate Ltd, Hitchin, United Kingdom
,
Toshko Lissitchkov
6   Clinic of Haematology, Specialized Hospital for Active Treatment of Haematological Diseases, Sofia, Bulgaria
,
Marcus May
7   Clinical Research Center Hannover, Hannover Medical School, Hannover, Germany
,
Irina Matytsina
8   Novo Nordisk A/S, Søborg, Denmark
,
Predrag Miljic
9   Clinic of Haematology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
,
Ingrid Pabinger
10   Clinical Division of Haematology and Haemostaseology, Medical University of Vienna, Vienna, Austria
,
Paula Persson
8   Novo Nordisk A/S, Søborg, Denmark
› Institutsangaben Funding This work was funded by Novo Nordisk A/S (Bagsværd, Denmark). Novo Nordisk's policy on data sharing may be found at https://www.novonordisk-trials.com/how-access-clinical-trial-datasets.
Weitere Informationen

Publikationsverlauf

13. Mai 2019

19. Oktober 2019

Publikationsdatum:
30. Dezember 2019 (online)

   Lizenzen und Reprints

Abstract

Background Factor VIII (FVIII) products are usually dosed according to body weight (BW). This may lead to under- or over-dosing in underweight or obese patients, respectively.

Objective This article evaluates the pharmacokinetics (PK) of recombinant FVIII concentrate, particularly recovery, in relation to body mass index (BMI) and other body composition descriptors.

Materials and Methods Thirty-five previously treated adults with severe haemophilia A from five BMI categories (underweight, normal, overweight, obese class I and II/III) were included. PK was evaluated after 50 IU per kilogram of BW single-dose recombinant FVIII (turoctocog alfa). The body composition variable was based on measurements of weight, height, bioimpedance analysis, and dual-energy X-ray absorptiometry. A dosing model was derived to achieve similar peak FVIII activity levels across BMI categories.

Results A statistically significant positive association between BMI and C30min, IR30min, and AUC0–inf was observed; CL and Vss showed a significant negative association with BMI; t½ was independent of BMI and other parameters. The dosing model introduced a correction factor ‘M’ for each BMI category, based on linear regression analysis of C30min against BMI, which ranged from 0.55 for underweight to 0.39 for obese class II/III. This model achieved similar peak FVIII activity levels across BMI categories, estimating an average dose adjustment of +243.3 IU (underweight) to –1,489.6 IU (obese class II/III) to achieve similar C30min.

Conclusion BMI appears to be the best predictor of recombinant FVIII recovery; however, PK endpoints were also dependent on other body composition variables. The model demonstrated that dosing can be adjusted for individual BMI to achieve better FVIII predictability across BMI categories.

Keywords

body mass index - dosing model - recombinant factor VIII - haemophilia - pharmacokinetics

Note

All authors confirm they have had full access to the data and contributed to the drafting of this manuscript.


Supplementary Material

 

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