• Sophie Dupuis-Girod, Sophie Rivière, Christian Lavigne, Anne-Emmanuelle Fargeton, Brigitte Gilbert-Dussardier, Vincent Grobost, Vanessa Leguy-Seguin, Hélène Maillard, Shirine Mohamed, Evelyne Decullier, Adeline Roux, Lorraine Bernard, Jean-Christophe Saurin, Nicolas Saroul, Frédéric Faure, Cesar Cartier, Romain Altwegg, Laurent Laccourreye, Frédéric Oberti, Marjolaine Beaudoin, Carole Dhelens, Céline Desvignes, Nicolas Azzopardi, Gilles Paintaud, Ruben Hermann, and Thierry Chinet.
• Service de Génétique et centre de référence de la maladie de Rendu-Osler, Hôpital Femme-Mère-Enfants, Hospices Civils de Lyon, Bron, France.
• J. Intern. Med. 2023 Dec 1; 294 (6): 761774761-774.

BackgroundBevacizumab-a humanized monoclonal antibody-has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted.MethodsThis study is a double-blind multicenter randomized phase 2 trial with a 1:1 active-treatment-to-placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3-month period before and after treatment.ResultsA total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention-to-treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (p = 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (p = 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (p = 0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm.ConclusionThough the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure.© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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