Dataset Information

Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia.

ABSTRACT: BACKGROUND:Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic inherited vascular dysplasia that leads to nosebleeds and visceral arteriovenous malformations (AVMs). Anti-angiogenic drugs thalidomide and bevacizumab have been increasingly used off-label with variable results. The HHT working group within the ERN for Rare Multisystemic Vascular Diseases (VASCERN), developed a questionnaire-based retrospective capture of adverse events (AEs) classified using the Common Terminology Criteria for Adverse Events. RESULTS:Sixty-nine HHT patients received bevacizumab, 37 (50.6%) for high output cardiac failure/hepatic AVMs, and 32 (49.4%) for bleeding; the 69 patients received bevacizumab for a mean of 11?months for a total of 63.8 person/years treatment. 67 received thalidomide, all for epistaxis and/or gastrointestinal bleeding; they received thalidomide for a mean of 13.4?months/patient for a total of 75 person/years treatment. AEs were reported in 58 patients, 33 with bevacizumab, 37 with thalidomide. 32 grade 1-3 AEs related to bevacizumab were reported with an average incidence rate of 50 per 100 person-years. 34 grade 1-3 AEs related to thalidomide were reported with an average incidence rate of 45.3 per 100 person-years. Bevacizumab AEs were more common in females (27 AEs in 46 women) than males (6 in 23, p?

SUBMITTER: Buscarini E

PROVIDER: S-EPMC6360670 | biostudies-other | 2019 Feb

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia.

Buscarini Elisabetta E Botella Luisa Maria LM Geisthoff Urban U Kjeldsen Anette D AD Mager Hans Jurgen HJ Pagella Fabio F Suppressa Patrizia P Zarrabeitia Roberto R Dupuis-Girod Sophie S Shovlin Claire L CL

Orphanet journal of rare diseases 20190204 1

<h4>Background</h4>Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic inherited vascular dysplasia that leads to nosebleeds and visceral arteriovenous malformations (AVMs). Anti-angiogenic drugs thalidomide and bevacizumab have been increasingly used off-label with variable results. The HHT working group within the ERN for Rare Multisystemic Vascular Diseases (VASCERN), developed a questionnaire-based retrospective capture of adverse events (AEs) classified using the Common Terminolo ...[more]

PMID: 30717761

Similar Datasets

Project description:BackgroundHereditary hemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolism and/or atrial fibrillation. Over decades, tolerance data has been published for almost 200 HHT-affected users of warfarin and heparins, but there are no published data for the newer direct oral anticoagulants (DOACs) in HHT.MethodsTo provide such data, a retrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN), in Denmark, France, Germany, Italy, the Netherlands and the UK.ResultsAlthough HHT Centres had not specifically recommended the use of DOACs, 32 treatment episodes had been initiated by other clinicians in 28 patients reviewed at the Centres, at median age 65 years (range 30-84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes). The 32 treatment episodes used Apixaban (n = 15), Rivaroxaban (n = 14), and Dabigatran (n = 3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15 (26.7%) Apixaban episodes and 7/14 (50%) Rivaroxaban episodes. By a 4 point scale of increasing severity, there was a trend for Rivaroxaban to be associated with a greater bleeding risk both including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associations were maintained after adjustment for gender and treatment indication. Extreme hemorrhagic responses, worse than anything experienced previously, with individual nosebleeds lasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in 5/14 (35.7%) Rivaroxaban episodes compared to 3/15 (20%) Apixaban episodes and published rates of ~ 5% for warfarin and heparin.ConclusionsCurrently, conventional heparin and warfarin remain first choice anticoagulants in HHT. If newer anticoagulants are considered, although study numbers are small, at this stage Apixaban appears to be associated with lesser bleeding risk than Rivaroxaban.

Project description:Background and purposeThe presence of malformations of cortical development in patients with hereditary hemorrhagic telangiectasia has been reported on previous occasions. We evaluated a sample of adults with hereditary hemorrhagic telangiectasia for the presence of malformations of cortical development, spatial coincidence of malformations of cortical development and AVMs, and the coincidence of brain and pulmonary AVMs.Materials and methodsA total of 141 patients 18 years of age or older who were referred to the Augusta University hereditary hemorrhagic telangiectasia clinic and underwent brain MR imaging between January 19, 2018, and December 3, 2020, were identified. MR imaging examinations were reviewed retrospectively by 2 experienced neuroradiologists, and the presence of malformations of cortical development and AVMs was confirmed by consensus. Demographic and clinical information was collected for each case, including age, sex, hereditary hemorrhagic telangiectasia status by the Curacao Criteria, mutation type, presence of malformations of cortical development, presence of brain AVMs, presence of pulmonary AVMs, and a history of seizures or learning disabilities.ResultsFive of 141 (3.5%) patients with hereditary hemorrhagic telangiectasia had malformations of cortical development. Two of the 5 patients with polymicrogyria also had closed-lip schizencephaly. One of the patients had a porencephalic cavity partially lined with heterotopic GM. The incidence of spatially coincident polymicrogyria and brain AVMs was 40% (2/5 cases). Of the patients with hereditary hemorrhagic telangiectasia and malformations of cortical development, 4/5 (80%) had pulmonary AVMs and 2/5 (40%) had brain AVMs.ConclusionsTo our knowledge, we are the first group to report the presence of schizencephaly in patients with hereditary hemorrhagic telangiectasia. The presence of schizencephaly and porencephaly lends support to the hypothesis of regional in utero cerebral hypoxic events as the etiology of malformations of cortical development in hereditary hemorrhagic telangiectasia.

Dataset Information

Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia.

Publications

Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets