Evolution of angiogenic and inflammatory biomarkers in patients with hereditary hemorrhagic telangiectasia during treatment with bevacizumab: study protocol.

Abstract

Background: Hereditary haemorrhagic telangiectasia (HHT) is a rare disease characterized by mucocutaneous telangiectasia and visceral vascular malformations. Treatment with bevacizumab is recommended in patients with liver involvement and high output heart failure (HOHF) or those with severe gastrointestinal (GI) involvement. However, there is no evidence on how to monitor such treatment using biomarkers.

Material and methods: This is an exploratory, observational, prospective, single-centre study carried out in an HHT referral unit. The inclusion period for the start of bevacizumab was from January 2022 to May 2023. Patients with an indication for starting bevacizumab were selected and underwent blood tests at baseline and during the induction (36 weeks) and maintenance phases to analyse 21 biomarkers related to angiogenesis and inflammation. In addition, control HHT patients without indication for bevacizumab and healthy controls matched 1:1:1 by age, sex, and genetic subtype (for HHT patients) underwent a baseline biomarker study. The main objective was to analyse the evolution of these biomarkers in patients with HHT treated with bevacizumab. As secondary objectives, baseline differences in the concentration of these biomarkers between the three groups and correlation with the haemoglobin levels were analysed.

Groups description: During the study period, nine patients with an indication for bevacizumab were included, seven due to anaemia of GI origin and two due to liver involvement with HOHF, with an overall mean age of 70 ± 8.4 years. Subsequently, the respective nine patients with HHT without bevacizumab and nine controls without HHT were selected.

Conclusions: The results of this exploratory study will provide new knowledge regarding potential biomarkers for monitoring the response to treatment with bevacizumab. Furthermore, it could generate new hypotheses about the role of certain biomarkers at the pathophysiological, diagnostic, and therapeutic levels.