PMID- 30717761 OWN - NLM STAT- MEDLINE DCOM- 20190419 LR - 20231005 IS - 1750-1172 (Electronic) IS - 1750-1172 (Linking) VI - 14 IP - 1 DP - 2019 Feb 4 TI - Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia. PG - 28 LID - 10.1186/s13023-018-0982-4 [doi] LID - 28 AB - 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. FAU - Buscarini, Elisabetta AU - Buscarini E AUID- ORCID: 0000-0003-0863-0624 AD - VASCERN HHT Reference Center, ASST Maggiore Hospital, Crema, Italy. elisabetta.buscarini@asst-crema.it. FAU - Botella, Luisa Maria AU - Botella LM AD - Department of Cell and Molecular Medicine Centro de Investigaciones Biologicas, CSIC, U707 CIBERER, Madrid, Spain. FAU - Geisthoff, Urban AU - Geisthoff U AD - VASCERN HHT Reference Center, Essen University Hospital, Department of Otorhinolaryngology, University of Duisburg-Essen, Essen, Germany. FAU - Kjeldsen, Anette D AU - Kjeldsen AD AD - VASCERN HHT Reference Center, Odense Universitetshospital, Syddansk Universitet, Odense, Denmark. FAU - Mager, Hans Jurgen AU - Mager HJ AD - VASCERN HHT Reference Center, St Antonius Ziekenhuis, Nieuwegein, Netherlands. FAU - Pagella, Fabio AU - Pagella F AD - VASCERN HHT Reference Center, Unita Operativa Complessa di Otorinolaringoiatria, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy. FAU - Suppressa, Patrizia AU - Suppressa P AD - VASCERN HHT Reference Center, Centro sovraziendale Malattie rare, "Frugoni" Internal Medicine Unit, University of Bari "A. Moro", Bari, Italy. FAU - Zarrabeitia, Roberto AU - Zarrabeitia R AD - HHT Unit, Hospital Sierrallana, Cantabria, Spain. FAU - Dupuis-Girod, Sophie AU - Dupuis-Girod S AD - VASCERN HHT Reference Center, Genetic department, Hospices Civils de Lyon, Femme-Mere-Enfants Hospital, F-69677, Bron, France. FAU - Shovlin, Claire L AU - Shovlin CL AD - VASCERN HHT Reference Center, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, and Vascular Sciences, National Heart and Lung Institute, Imperial College London, London, UK. CN - VASCERN-HHT LA - eng PT - Journal Article DEP - 20190204 PL - England TA - Orphanet J Rare Dis JT - Orphanet journal of rare diseases JID - 101266602 RN - 2S9ZZM9Q9V (Bevacizumab) RN - 4Z8R6ORS6L (Thalidomide) SB - IM MH - Adolescent MH - Adult MH - Bevacizumab/*adverse effects/therapeutic use MH - Epistaxis/drug therapy/metabolism/physiopathology MH - Female MH - Hemorrhage/drug therapy/metabolism/physiopathology MH - Humans MH - Male MH - Retrospective Studies MH - Surveys and Questionnaires MH - Telangiectasia, Hereditary Hemorrhagic/drug therapy/metabolism/*physiopathology MH - Thalidomide/*adverse effects/therapeutic use MH - Young Adult PMC - PMC6360670 OTO - NOTNLM OT - Adverse event OT - Arteriovenous malformation OT - Bevacizumab OT - Bleeding OT - Cardiac failure OT - Epistaxis OT - Hereditary hemorrhagic telangiectasia OT - Nosebleeds OT - Thalidomide COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The survey was ethically approved. CONSENT FOR PUBLICATION: Not applicable COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. FIR - Federici, Paolo IR - Federici P FIR - Crocione, Claudia IR - Crocione C EDAT- 2019/02/06 06:00 MHDA- 2019/04/20 06:00 PMCR- 2019/02/04 CRDT- 2019/02/06 06:00 PHST- 2018/09/03 00:00 [received] PHST- 2018/12/14 00:00 [accepted] PHST- 2019/02/06 06:00 [entrez] PHST- 2019/02/06 06:00 [pubmed] PHST- 2019/04/20 06:00 [medline] PHST- 2019/02/04 00:00 [pmc-release] AID - 10.1186/s13023-018-0982-4 [pii] AID - 982 [pii] AID - 10.1186/s13023-018-0982-4 [doi] PST - epublish SO - Orphanet J Rare Dis. 2019 Feb 4;14(1):28. doi: 10.1186/s13023-018-0982-4.