{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:02:39Z","timestamp":1791932559593,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bevacizumab\u2014a humanized monoclonal antibody\u2014has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study is a double\u2010blind multicenter randomized phase 2 trial with a 1:1 active\u2010treatment\u2010to\u2010placebo 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\u00a0mg\/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\u2010month period before and after treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention\u2010to\u2010treat 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% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.03). Fifty\u2010nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.13714","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T21:47:12Z","timestamp":1692654432000},"page":"761-774","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial"],"prefix":"10.1111","volume":"294","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8834-5526","authenticated-orcid":false,"given":"Sophie","family":"Dupuis\u2010Girod","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et centre de r\u00e9f\u00e9rence de la maladie de Rendu\u2010Osler H\u00f4pital Femme\u2010M\u00e8re\u2010Enfants, Hospices Civils de Lyon  Bron France"},{"name":"Inserm, CEA, Laboratory Biology of Cancer and Infection Universit\u00e9 Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Rivi\u00e8re","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Interne A Centre Hospitalier Universitaire  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lavigne","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine interne\u2010Immunologie clinique CHU d'Angers  Angers cedex 09 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Emmanuelle","family":"Fargeton","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et centre de r\u00e9f\u00e9rence de la maladie de Rendu\u2010Osler H\u00f4pital Femme\u2010M\u00e8re\u2010Enfants, Hospices Civils de Lyon  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Gilbert\u2010Dussardier","sequence":"additional","affiliation":[{"name":"Service de g\u00e9n\u00e9tique m\u00e9dicale CHU La Mil\u00e9trie  Poitiers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5352-7949","authenticated-orcid":false,"given":"Vincent","family":"Grobost","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Interne CHU Estaing Clermont\u2010Ferrand University Hospital  Clermont\u2010Ferrand France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Leguy\u2010Seguin","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Interne 1 CHU Francois Mitterrand  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Maillard","sequence":"additional","affiliation":[{"name":"CHU Lille Service de M\u00e9decine Interne et Immunologie Clinique  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirine","family":"Mohamed","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine interne et Immunologie Clinique CHRU BRABOIS  Vandoeuvre\u2010l\u00e8s\u2010Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Decullier","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon P\u00f4le Sant\u00e9 Publique  Lyon France"},{"name":"Facult\u00e9 de m\u00e9decine Universit\u00e9 Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Roux","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon P\u00f4le Sant\u00e9 Publique  Lyon France"},{"name":"Facult\u00e9 de m\u00e9decine Universit\u00e9 Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Bernard","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon P\u00f4le Sant\u00e9 Publique  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Christophe","family":"Saurin","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de m\u00e9decine Universit\u00e9 Lyon 1  Lyon France"},{"name":"Hospices Civils de Lyon, Service d'H\u00e9pato\u2010gastroent\u00e9rologie H\u00f4pital E. 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