Intra-venous bevacizumab in hereditary hemorrhagic telangiectasia (HHT): A retrospective study of 46 patients

<div><p>Background</p><p>Bevacizumab, an anti-VEGF monoclonal antibody, has recently emerged as a new option for severe forms of hereditary hemorrhagic telangiectasia (HHT). Its utilization in this orphan disease has rapidly spread despite the lack of randomized trials and international guidelines. The objective of this study is to report the main clinical data (baseline characteristics, dose schedule, efficacy, adverse events and deaths) of HHT patients treated by intravenous bevacizumab in France.</p><p>Methods</p><p>Retrospective observational study of HHT patients treated with bevacizumab for a severe form of the disease in the 14 centers of the French HHT network.</p><p>Results</p><p>Forty-six patients (median age: 68 years) were treated between March 2009 and May 2015. Ten patients were treated for high output cardiac failure, 20 patients for severe hemorrhages and 16 for both indications. The standard protocol (6 infusions of 5mg/kg every 2 weeks) was initially used in 89% of the cases but diverse strategies were subsequently applied. A clinical improvement was noted by the referent physician for 74% of the patients with a median effect’s duration of 6 months. Wound healing complications led to 2 amputations. Arthralgia/arthritis and arterial hypertension occurred in 5 patients each. One third of the patients were dead at the time of the final update, coherently with age and the poor prognosis of these highly symptomatic patients.</p><p>Conclusion</p><p>Intravenous bevacizumab seems to provide a clinical benefice in severe HHT patients. Precautions concerning wound healing and vascular pathologies must be respected. Prospective double blinded versus placebo trials are needed.</p></div

Recommendations for the use of intra-venous bevacizumab in HHT patients.

<p>Recommendations for the use of intra-venous bevacizumab in HHT patients.</p

Patient’s characteristics before treatment (n = 46).

<p>Patient’s characteristics before treatment (n = 46).</p

Initial severity of disease, modalities of use, efficacy and safety of bevacizumab.

<p>Initial severity of disease, modalities of use, efficacy and safety of bevacizumab.</p

Pulmonary hypertension subtypes associated with hereditary haemorrhagic telangiectasia: Haemodynamic profiles and survival probability

<div><p>Background</p><p>Different pulmonary hypertension (PH) mechanisms are associated with hereditary haemorrhagic telangiectasia (HHT).</p><p>Methods and results</p><p>We conducted a retrospective study of all suspected cases of PH (echocardiographically estimated systolic pulmonary artery pressure [sPAP] ≥ 40 mmHg) in patients with definite HHT recorded in the French National Reference Centre for HHT database. When right heart catheterization (RHC) was performed, PH cases were confirmed and classified among the PH groups according to the European guidelines. Among 2,598 patients in the database, 110 (4.2%) had suspected PH. Forty-seven of these 110 patients had RHC: 38/47 (81%) had a confirmed diagnosis of PH. The majority of these had isolated post-capillary PH (n = 20). We identified for the first time other haemodynamic profiles: pre-capillary pulmonary arterial hypertension (PAH) cases (n = 3) with slightly raised pulmonary vascular resistances (PVR), and combined post- and pre-capillary PH cases (n = 4). Compared to controls, survival probability was lower in patients with PAH.</p><p>Conclusion</p><p>This study revealed the diversity of PH mechanisms in HHT. The description of combined post- and pre-capillary PH with/or without high cardiac output (CO) suggests either a continuum between the pre- and post-capillary haemodynamic profiles or a different course in response to high CO.</p></div

Haemodynamic profiles of patients in Group 1.

<p>Haemodynamic profiles of patients in Group 1.</p

Haemodynamic profiles of patients in Group 1.

<p>Haemodynamic profiles of patients in Group 1.</p

Flow chart of HHT patients selected for the study.

<p>CO, cardiac output; HA, hepatic artery; HHT, hereditary haemorrhagic telangiectasia; sPAP, systolic pulmonary artery pressure; mPAP, mean pulmonary artery pressure; dPAP, diastolic pulmonary artery pressure; PH, pulmonary hypertension; PVR, pulmonary vascular resistances; PAWP, pulmonary artery wedge pressure; RHC, right heart catheterization; WU, Wood units.</p

Comparison of phenotypic and genotypic characteristics between patients with echocardiographic suspicion of PH and controls.

<p>Comparison of phenotypic and genotypic characteristics between patients with echocardiographic suspicion of PH and controls.</p

Comparison of life expectancy between Groups 1 and 2 and then between heritable Group 1 and isolated Group 2 patients with PH confirmed by RHC and controls with normal echocardiographic findings.

<p>HHT, hereditary haemorrhagic telangiectasia; PAH, pulmonary arterial hypertension; PH, pulmonary hypertension.</p