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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2019

Open Access 01-12-2019 | Heart Failure | Research

Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia

Authors: Elisabetta Buscarini, Luisa Maria Botella, Urban Geisthoff, Anette D. Kjeldsen, Hans Jurgen Mager, Fabio Pagella, Patrizia Suppressa, Roberto Zarrabeitia, Sophie Dupuis-Girod, Claire L. Shovlin, on behalf of VASCERN-HHT

Published in: Orphanet Journal of Rare Diseases | Issue 1/2019

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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 < 0.001). Thalidomide AEs occurred at more similar rates in males (25 AEs in 41 men, 60.9%) and females (12 in 26 (46.2%), but were more common in ENG patients (17 in 17) than in ACVRL1 (14 in 34, p < 0.0001). For bevacizumab, the most common reports were of joint pains (7/69, 10%), headache (3/69, 4.4%) and proteinuria (2/69, 3%), and for thalidomide, peripheral neuropathy (12/67, 18%); drowsiness (8/67, 12%); and dizziness (6/67, 9%). Fatal adverse events were more common in males (p = 0.009), and in patients with ENG pathogenic variants (p = 0.012). One fatal AE was possibly related to bevacizumab (average incidence rate: 1.5 per 100 person-years); 3 fatal AEs were possibly related to thalidomide (average incidence rate: 4 per 100 person-years).

Conclusions

With potential increase in use of Bevacizumab and Thalidomide in HHT patients, data presented support appropriate weighing of the toxicities which can arise in HHT settings and the practice recommendations for their prevention and management.
Appendix
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Metadata
Title
Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia
Authors
Elisabetta Buscarini
Luisa Maria Botella
Urban Geisthoff
Anette D. Kjeldsen
Hans Jurgen Mager
Fabio Pagella
Patrizia Suppressa
Roberto Zarrabeitia
Sophie Dupuis-Girod
Claire L. Shovlin
on behalf of VASCERN-HHT
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2019
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-018-0982-4

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