Guilhem Alexandre, Fargeton Anne-Emmanuelle, Simon Anne-Claire, Duffau Pierre, Harle Jean-Robert, Lavigne Christian, Carette Marie-France, Bletry Olivier, Kaminsky Pierre, Leguy Vanessa, Lerolle Nathalie, Roux Dominique, Lambert Marc, Chinet Thierry, Bonnet Delphine, Dupuis-Girod Sophie, Rivière Sophie
Médecine Interne - Maladies Multi-Organiques, Hôpital Saint Eloi, Montpellier, France.
Service de Génétique - Centre de Référence National Maladie de Rendu-Osler, Hôpital Femme-Mère-Enfant, Bron, France.
PLoS One. 2017 Nov 30;12(11):e0188943. doi: 10.1371/journal.pone.0188943. eCollection 2017.
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.
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.
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.
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.
贝伐单抗,一种抗血管内皮生长因子(VEGF)单克隆抗体,最近已成为重症遗传性出血性毛细血管扩张症(HHT)的一种新选择。尽管缺乏随机试验和国际指南,但这种孤儿病药物的使用仍迅速普及。本研究的目的是报告在法国接受静脉注射贝伐单抗治疗的HHT患者的主要临床数据(基线特征、剂量方案、疗效、不良事件和死亡情况)。
对法国HHT网络14个中心接受贝伐单抗治疗重症HHT的患者进行回顾性观察研究。
2009年3月至2015年5月期间,共治疗了46例患者(中位年龄:68岁)。10例患者因高输出量心力衰竭接受治疗,20例因严重出血接受治疗,16例因上述两种情况均接受治疗。最初89%的病例采用标准方案(每2周6次输注,每次5mg/kg),但随后采用了多种策略。转诊医生指出,74%的患者有临床改善,中位疗效持续时间为6个月。伤口愈合并发症导致2例截肢。5例患者出现关节痛/关节炎,5例出现动脉高血压。在最后一次更新时,三分之一的患者死亡,这与这些症状严重患者的年龄和不良预后一致。
静脉注射贝伐单抗似乎能使重症HHT患者临床受益。必须注意伤口愈合和血管病变方面的问题。需要进行前瞻性双盲对照安慰剂试验。