Oral itraconazole for epistaxis in hereditary hemorrhagic telangiectasia: a proof of concept study
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ORIGINAL PAPER
Oral itraconazole for epistaxis in hereditary hemorrhagic telangiectasia: a proof of concept study S. Kroon1 · R. J. Snijder1 · A. E. Hosman1 · V. M.M. Vorselaars2 · F. J.M Disch3 · M. C. Post2 · J. J. Mager1 Received: 12 March 2020 / Accepted: 9 November 2020 © Springer Nature B.V. 2020
Abstract The inhibiting effects of itraconazole, an antifungal drug on vascular endothelial growth factor (VEGF) have recently been discovered. By inhibiting VEGF, itraconazole has shown potential in clinical trials as anti-cancer treatment. In hereditary hemorrhagic telangiectasia (HHT) patients, VEGF levels are elevated and inhibition of VEGF can decrease bleeding. Itraconazole could potentially serve as anti-angiogenic therapy for HHT-related bleeding. We report a proof of concept study with HHT patients and severe epistaxis. Patients were treated with daily 200 mg orally administered itraconazole for sixteen weeks. Twenty-one HHT patients, 8 females (38%), 13 males (62%), median age of 59 years (interquartile range (IQR) 55–69) were enrolled. Of these patients, 13 (62%) were diagnosed with HHT type 1, seven (33%) with HHT type 2 and in one patient (5%), no pathognomonic HHT mutation was found. Four patients (19%) prematurely terminated the study (3 due to mild or moderate side-effects) resulting in 17 patients included in the analyses. The median epistaxis severity score significantly decreased during treatment from 6.0 (IQR 5.1–7.2) to 3.8 (IQR 3.1–5.2) (p = 0.006). The monthly epistaxis frequency decreased from 56 to 38 epistaxis episodes (p = 0.004) and the monthly duration from 407 to 278 minutes (p = 0.005). Hemoglobin levels did not significantly change. The quality of life showed a small but significant improvement. In conclusion, oral itraconazole significantly improved epistaxis in HHT patients. The potential benefit of itraconazole in HHT should be further investigated. Keywords Anemia · Epistaxis · Telangiectasia, Hereditary hemorrhagic · Vascular endothelial growth factors Abbreviations ACVRL1 Activin A receptor like type 1 AE Adverse event APC Argon plasma coagulation ENG Endoglin Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10456-020-09758-2) contains supplementary material, which is available to authorized users.
ESS Epistaxis severity score HHT Hereditary hemorrhagic telangiectasia IQR Interquartile range MCS Mental component summary MFI-20 Multidimensional fatigue inventory 20 PCS Physical component summary RBC Red blood cell SAE Severe adverse event
* J. J. Mager [email protected]
M. C. Post [email protected]
S. Kroon [email protected]
1
R. J. Snijder [email protected]
Departments of Pulmonology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands
2
A. E. Hosman [email protected]
Department of Cardiology and Ear, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands
3
Department of Nose and Throat
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