Thalidomide for hereditary haemorrhagic telangiectasia

Abstract

4 Nevertheless, most of these measures are only palliative and the results are largely unsatisfactory, so patients with hereditary haemorrhagic telangiectasia and severe nosebleeds usually face important impediments to daily activities and have a poor quality of life. 5 Because abnormal angiogenesis has been implicated in the pathogenesis of hereditary haemorrhagic telangiectasia, research has been focused on the potential role of anti-angiogenic drugs such as bevacizumab and thalidomide. Systemic and topical use of bevacizumab, a monoclonal antibody antagonist of VEGF, has been investigated in a small number of patients with hereditary haemorrhagic telangiectasia who had severe epistaxis, yielding controversial outcomes. thalidomide treatment for most patients (ie, reduction of severity, frequency, and duration of nosebleeds; reduction of blood transfusion requirements; and increased median haemoglobin concentrations). A phase 2 study from Rosangela Invernizzi and colleagues in The Lancet Haematology brings a substantial advance in this topic. 9 In this clinical dose-escalation trial the researchers enrolled 31 patients with hereditary haemorrhagic telangiectasia and severe recurrent epistaxis. The patients received thalidomide at a starting daily dose of 50 mg, which was progressively increased up to 200 mg/day if they had no response. After a median follow-up of 15·9 months, the low dose of thalidomide (50 mg/day) was highly eff ective in reduction of the frequency, intensity, and duration of nose bleeds in 25 (81%) of 31 of patients, whereas all the remaining patients who were initially non-responders (six (19%) patients) had a response at increased doses of thalidomide (100-150 mg/day). Notably, the treatment signifi cantly increased patients' haemoglobin concentrations and prevented the need of transfusion in 20 (87%) of 23 patients who were dependent on of transfusions. Furthermore, the median time to relapse after the end of treatment with thalidomide was more than 6 months, which is consistent with the theory that the action of thalidomide is not only limited to the direct inhibition of endothelial cell proliferation, but also includes the induction of maturation of blood vessels that become more durable and less prone to bleeding. 10