Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial.

Abstract

Bevacizumab-a humanized monoclonal antibody-has been widely used to treat patients with hereditary hemorrhagic telangiectasia, but no randomized trial has yet been conducted. This study is a double-blind multi-center randomized phase 2 trial with a 1:1 active-treatment-to-placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell units transfused in the three months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of red blood cell units transfused in a three-month period before and after treatment. 24 patients (12 in each group) were included and randomized at four different centers. In intention-to-treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (p=0.22). Hemoglobin levels significantly improved at six months in the bevacizumab versus placebo group (p=0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in red blood cell transfusions (p=0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm. Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure. This article is protected by copyright. All rights reserved.