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Multicenter Study
. 2020 Feb;120(2):277-288.
doi: 10.1055/s-0039-3400745. Epub 2019 Dec 30.

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

Andreas Tiede  1 , Ana Rosa Cid  2 , Georg Goldmann  3 , Victor Jiménez-Yuste  4 , Michael Pluta  5 , Toshko Lissitchkov  6 , Marcus May  7 , Irina Matytsina  8 , Predrag Miljic  9 , Ingrid Pabinger  10 , Paula Persson  8
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Free article
Multicenter Study

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

Andreas Tiede et al. Thromb Haemost. 2020 Feb.
Free article

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.

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Conflict of interest statement

A.T. has received research support, honoraria or consultation fees from Alnylam, Bayer, Biogen Idec, Biotest, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire and SOBI. A.R.C. has received reimbursement for attending symposia/congresses and/or honoraria for speaking or consulting from Novo Nordisk and other companies. G.G. has received reimbursement for attending symposia/congresses and/or honoraria for speaking or consulting from Novo Nordisk and other companies. V.J.-Y. has received reimbursement for attending symposia/congresses and/or honoraria for speaking and/or honoraria for consulting, and/or funds for research from Bayer, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Shire and SOBI. M.P. is a paid consultant for Novo Nordisk A/S. T.L. has received investigator fees as a participant of the clinical trial from Novo Nordisk. M.M. has no conflicts of interest to declare. I.M. is an employee of Novo Nordisk A/S. P.M. has no conflicts of interest to declare. I.P. has received honoraria or consultation fees from Bayer, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Shire and SOBI; also research support from CSL Behring and Novo Nordisk. P.P. is an employee of Novo Nordisk A/S.

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