Dose - response relationship of bevacizumab in hereditary hemorrhagic telangiectasia

MAbs
Nicolas AzzopardiGilles Paintaud

Abstract

Hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder associated with epistaxis and hepatic shunts, is responsible for high-output cardiac failure in rare cases. Bevacizumab, which targets vascular endothelial growth factor, was shown to decrease both cardiac index (CI) and epistaxis duration in HHT patients with severe liver involvement. The relationship between its serum concentration and change in both CI and epistaxis duration was investigated to design the bevacizumab maintenance dosing regimen of future therapeutic studies. Twenty-five HHT patients with dyspnea and high CI were included in a prospective non-comparative study. They received bevacizumab at a dose of 5 mg/kg per infusion every 14 days for a total of 6 injections. The relationships between bevacizumab serum concentration and both CI and epistaxis duration were described using transit compartments and direct inhibition pharmacokinetic-pharmacodynamic models. The performances of different maintenance regimens were evaluated using simulation. Infusions every 3, 2 and one months were predicted to maintain 41%, 45% and 50% of patients with CI <4 L/min/m(2) at 24 months, respectively. The fraction of patients with <20 min epistaxis per month was ...Continue Reading

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Citations

Oct 16, 2015·Nature Reviews. Cardiology·Nicholas W MorrellKenneth D Bloch
Feb 23, 2018·The Laryngoscope·Johan SteinegerSinan Dheyauldeen
Oct 1, 2017·Circulation Research·Sara I CunhaMaria Grazia Lampugnani
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Jan 3, 2019·Ophthalmic Plastic and Reconstructive Surgery·Sathyadeepak RameshDaniel B Rootman
Sep 8, 2018·Angiogenesis·Marie E FaughnanDennis L Sprecher

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Methods Mentioned

BETA
ELISA
enzyme-linked immunosorbent assay

Clinical Trials Mentioned

NCT00843440

Software Mentioned

Monolix
R

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