Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with the most severe bleeding causing RBC transfusion dependence treated on a predefined institutional pazopanib treatment pathway (with data collected retrospectively). The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation, compared using paired and repeated measures mean tests. Thirteen transfusion-dependent HHT patients received pazopanib [median (range) dose 150 (25–300) mg daily)] for a median of 22 months. All patients achieved transfusion independence. Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6–5.9) g/dL (7.8 vs. 12.7 g/dL, P < 0.0001) and decreased mean epistaxis severity score by 4.77 (3.11–6.44) points (7.20 vs. 2.43 points, P < 0.0001) after 12 months of treatment. Compared with 3 months of pretreatment, RBC transfusions decreased by 93% (median of 16.0 vs. 0.0 units, P < 0.0001) and elemental iron infusion decreased by 92% (median of 4500 vs. 0 mg, P = 0.005) during the first 3 months of treatment; improvements were maintained over time. Pazopanib was well-tolerated: hypertension, lymphocytopenia, and fatigue were the most common TEAEs. In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patients from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial.

遗传性出血性毛细血管扩张症 (HHT) 是一种罕见的血管生成疾病，可导致慢性胃肠道出血、鼻出血和严重贫血。帕唑帕尼是一种口服多激酶血管生成抑制剂，有望治疗 HHT 出血。我们分析了使用预先确定的机构帕唑帕尼治疗途径治疗的最严重出血导致红细胞输血依赖的 HHT 患者的结果（回顾性收集数据）。主要终点是实现输血独立。次要终点包括血红蛋白、鼻出血严重程度评分、红细胞输血和铁输注要求、局部止血手术次数、铁蛋白和转铁蛋白饱和度，并使用配对和重复测量平均值检验进行比较。13 名输血依赖性 HHT 患者接受帕唑帕尼 [中位（范围）剂量 150（25-300）mg 每天）]，中位时间为 22 个月。所有患者都实现了输血独立。与预处理相比，帕唑帕尼使平均血红蛋白增加 4.8 (95% CI, 3.6–5.9) g/dL (7.8 vs. 12.7 g/dL,P < 0.0001) 并且 在治疗 12 个月后 平均鼻出血严重程度评分降低了 4.77 (3.11–6.44) 分（7.20 对 2.43 分，P < 0.0001）。与治疗前 3 个月相比，RBC 输血减少了 93%（中位数为 16.0 对 0.0 单位，P  < 0.0001），元素铁输注减少了 92%（中位数 4500 对 0 mg，P = 0.005) 在治疗的前 3 个月内；随着时间的推移不断改进。帕唑帕尼耐受性良好：高血压、淋巴细胞减少和疲劳是最常见的 TEAE。总之，帕唑帕尼治疗 HHT 的严重出血是安全和有效的，使所有患者摆脱输血依赖，并使血液学参数正常化，剂量低于用于治疗恶性肿瘤的剂量。这些发现需要在随机试验中得到证实。