Efficacy of intranasal bevacizumab (Avastin) treatment in patients with hereditary hemorrhagic telangiectasia‐associated epistaxis

Abstract

In HHT patients intranasal Bevacizumab, applied as a topical spray or a submucosal injection, significantly improves epistaxis as measured by the Epistaxis Severity Score.

ELLIPSE Study

“…Patients were carefully followed for nasal cartilaginous septum perforations which have been described as a side effect of intravenous bevacizumab in cancer patients. [18][19][20][21] This complication was also described after bevacizumab submucosal injections 14,22 or laser treatments but never with topical treatments. In this study, nasal cartilaginous septum perforation was not observed following treatment administration.…”

“…In the literature, several case reports and pilot studies reported a potential effect of bevacizumab nasal spray on epistaxis in HHT, with different doses and frequency of administration. 13,14,22,25 However, the frequency of epistaxis is highly variable in a given patient and between patients and it is currently not possible to conclude on efficacy based on those reports. We can hypothesize that a one-day treatment is not enough to act on epistaxis and that a single drug administration does not expose nasal mucosal tissue to bevacizumab in levels sufficient to improve epistaxis.…”

“…10 Furthermore, several published cases reported a potential efficacy of bevacizumab nasal spray. [11][12][13][14][15] Our primary aim in the study reported here was to evaluate the safety in humans of a bevacizumab nasal spray. The secondary objectives were 2-fold: (1) to study systemic passage and the pharmacokinetics of bevacizumab in blood after nasal spray delivery; and (2) to evaluate efficacy on epistaxis (duration and number), on anemia (hemoglobinemia and ferritinemia) and on the number of blood transfusions.…”

Hereditary haemorrhagic telangiectasia

“…However, its side effect profile includes spontaneous gastrointestinal perforation, cytopaenia, hypertension, delayed wound healing, septal perforation, weakness and haemorrhage, concerns about which have understandably limited its use for epistaxis alone; it is also expensive and long-term maintenance treatment is required as its effect is not permanent (58,79) . To try and mitigate these side effects, it has also been used intranasally, both as submucosal injections and in spray form (81)(82)(83)(84)(85)(86)(87)(88)(89)(90) . Whilst most authors report reasonable efficacy with no/minimal side effects, there have been concerns regarding the development of septal perforations following submucosal injection (81,83) .…”

“…Whilst most authors report reasonable efficacy with no/minimal side effects, there have been concerns regarding the development of septal perforations following submucosal injection (81,83) . Most authors therefore advise against injecting bevacizumab over the cartilaginous septum (81,83,84,86) . The optimum dose and route of administration have not yet been found, although extended systemic dosing intervals (three-to four-weekly) and very low dose systemic bevacizumab have been suggested (91,92) .…”