Effect of Bevacizumab Nasal Spray on Epistaxis Duration in Hereditary Hemorrhagic Telangectasia

Dupuis‐Girod, Sophie; Ambrun, A.; Decullier, Évelyne; Fargeton, Anne-Emmanuelle; Roux, Adeline; Bréant, V.; Colombet, Bettina; Rivière, Sophie; Cartier, C.; Lacombe, Pascal; Chinet, Thierry; Blivet, Sandra; Blondel, Jean-Hugues; Gilbert‐Dussardier, Brigitte; Dufour, Xavier; Michel, J.; Harlé, Jean‐Robert; Dessi, P.; Faure, Frédéric

doi:10.1001/jama.2016.11387

Cited by 59 publications

(103 citation statements)

References 27 publications

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“…Recently, two different multicenter, double‐blind, placebo‐controlled randomized clinical trials were conducted, investigating the efficacy of bevacizumab spray in reducing HHT‐associated epistaxis. Both studies failed to show any benefit of bevacizumab spray compared to placebo . Endonasal crusting impairing spray delivery and the large size of the molecule of the drug impeding permeability through the mucosal membrane may be possible reasons for this.…”

Section: Discussionmentioning

confidence: 99%

Long‐term experience with intranasal bevacizumab therapy

Steineger¹,

Osnes

Heimdal

et al. 2018

The Laryngoscope

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Section: Discussionmentioning

confidence: 99%

Long‐term experience with intranasal bevacizumab therapy

Steineger¹,

Osnes

Heimdal

et al. 2018

The Laryngoscope

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“…These observations are in line with several early-phase clinical trials supporting that bevacizumab treatments—using topical, submucosal, or i.v. infusion routes—were effective at reducing epistaxis in HHT patients484950, but see also refs 51 and 52.…”

Section: Discussionmentioning

confidence: 99%

A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10

Ruíz

Zhao

Chandakkar

et al. 2016

Sci Rep

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Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening genetic vascular disorder caused by loss-of-function mutations in the genes encoding activin receptor-like kinase 1 (ALK1), endoglin, Smad4, and bone morphogenetic protein 9 (BMP9). Injections of mouse neonates with BMP9/10 blocking antibodies lead to HHT-like vascular defects in the postnatal retinal angiogenesis model. Mothers and their newborns share the same immunity through the transfer of maternal antibodies during lactation. Here, we investigated whether the transmammary delivery route could improve the ease and consistency of administering anti-BMP9/10 antibodies in the postnatal retinal angiogenesis model. We found that anti-BMP9/10 antibodies, when intraperitoneally injected into lactating dams, are efficiently transferred into the blood circulation of lactationally-exposed neonatal pups. Strikingly, pups receiving anti-BMP9/10 antibodies via lactation displayed consistent and robust vascular pathology in the retina, which included hypervascularization and defects in arteriovenous specification, as well as the presence of multiple and massive arteriovenous malformations. Furthermore, RNA-Seq analyses of neonatal retinas identified an increase in the key pro-angiogenic factor, angiopoietin-2, as the most significant change in gene expression triggered by the transmammary delivery of anti-BMP9/10 antibodies. Transmammary-delivered BMP9/10 immunoblocking in the mouse neonatal retina is therefore a practical, noninvasive, reliable, and robust model of HHT vascular pathology.

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“…Dupuis-Girod et al 12 compared a placebo group and three groups receiving different doses of bevacizumab (25, 50 or 75 mg per treatment) administered as a nasal spray (three sprays 14 days apart for a total treatment duration of 4 weeks), resulting in total doses of 75 mg, 150 mg and 225 mg in the bevacizumab treatment groups. In the other clinical trials,13 patients received twice-daily nose sprays for 12 weeks with either bevacizumab 1% (4 mg/day), estriol 0.1% (0.4 mg/day), tranexamic acid 10% (40 mg/day) or placebo (0.9% saline).…”

Section: Discussionmentioning

confidence: 99%

Intranasal bevacizumab treatment on epistaxis in hereditary haemorrhagic telangiectasia: a case report

et al. 2017

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Hereditary haemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a rare, vascular, autosomal dominant disorder. The purpose of this paper is to describe the efficacy and safety of treatment with intranasal bevacizumab in HHT.A 42-year-old woman with HHT presented with frequent episodes of epistaxis. Iron studies showed anaemia of iron deficiency from chronic blood loss. Because of the frequent epistaxis (Epistaxis Severity Score (ESS) 6.76) and varying haemoglobin levels (Hb range: 7.7–9.9g/dL) her doctors sought treatment with intranasal bevacizumab. This treatment was prescribed at the hospital pharmacy department in a laminar flow hood. 2.5 mL (25 mg) were placed in a nasal spray bottle. The recommended dosage was twice a day for two consecutive months. Nasal treatment seemed to control her epistaxis, and no adverse effects were reported. She only had a few further minor episodes of epistaxis, which were easily controlled (ESS 3.44). The haemoglobin levels evreached normal levels (Hb range: 12.8–14.1g/dL).

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Effect of Bevacizumab Nasal Spray on Epistaxis Duration in Hereditary Hemorrhagic Telangectasia

Cited by 59 publications

References 27 publications

Long‐term experience with intranasal bevacizumab therapy

Long‐term experience with intranasal bevacizumab therapy

A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10

Intranasal bevacizumab treatment on epistaxis in hereditary haemorrhagic telangiectasia: a case report

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