Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial

Hospices Civils de Lyon, Hôpital Femme-Mère-Enfants, Service de Génétique et centre de référence de la maladie de Rendu-Osler, Bron, F-69677, France. Inserm, CEA, Laboratory Biology of Cancer and Infection, Univ. Grenoble Alpes, Grenoble, F-38000, France. Service de Médecine Interne A, Centre Hospitalier Universitaire, Montpellier, F-34000, France. Service de médecine interne-Immunologie clinique, CHU d'Angers, Angers, F-49933, France. Service de génétique médicale, CHU La Milétrie, Poitiers, F-86021, France. Service de Médecine Interne CHU Estaing, Clermont-Ferrand University Hospital, Clermont-Ferrand, F-63100, France. Service de Médecine Interne 1, CHU Francois Mitterrand, DIJON, F-21000, France. CHU Lille, Service de Médecine Interne et Immunologie Clinique, Lille, F-59000, France. Département de Médecine interne et Immunologie Clinique, CHRU BRABOIS, Vandoeuvre-lès-Nancy, F-54500, France. Hospices Civils de Lyon, Pôle Santé Publique, Lyon, F-69003, France. Faculté de médecine, Université Lyon 1, Lyon, F-69008, France. Hospices Civils de Lyon, Service d'Hépato-gastroentérologie, Hôpital E. Herriot, Lyon, F-69437, France. CHU Clermont Ferrand, Hôpital Gabriel Montpied, Service d'ORL, Clermont-Ferrand, F-63100, France. Hospices Civils de Lyon, Hôpital E. Herriot, Service d'ORL, Lyon, F-69437, France. Service d'ORL Centre Hospitalier Universitaire, Montpellier, F-34000, France. Service Hépatogastroentérologie CHU St Eloi, Montpellier, F-34000, France. Service d'ORL, CHU d' Angers, Angers, F-49933, France. Service Hépatogastroentérologie, UPRES EA 3859, Faculté de médecine, CHU Angers and Laboratoire HIFIH, Angers, France. Hospices Civils de Lyon, Hôpital Edouard Herriot, Pharmacie à Usage Intérieur, Lyon, F-69437, France. CHRU de Tours, Plateforme Recherche, Centre Pilote de suivi Biologique des traitements par Anticorps (CePiBAc), Tours, France. EA 4245 Transplantation, Immunologie, Inflammation (T2I), Université de Tours, Tours, France. CNRS EMR 7001 LNOx, Université de Tours, Tours, France. Service de Pharmacologie Médicale, CHRU de Tours, Tours, France. Hospices Civils de Lyon, Hôpital Femme-Mère-Enfants, Service d'ORL et centre de référence de la maladie de Rendu-Osler, Bron, F-69677, France. Centre Rendu-Osler, Hôpital Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Université de Versailles SQY, Boulogne, F-92100, France.

Journal of internal medicine. 2023
Abstract
BACKGROUND Bevacizumab-a humanized monoclonal antibody-has been widely used to treat patients with hereditary hemorrhagic telangiectasia, but no randomized trial has yet been conducted. METHODS This study is a double-blind multi-center 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 units transfused in the three 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 red blood cell units transfused in a three-month period before and after treatment. RESULTS 24 patients (12 in each group) were included and randomized at four 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 six 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 red blood cell transfusions (p = 0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm. CONCLUSION Though 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. This article is protected by copyright. All rights reserved.
Study details
Language : eng
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