贝伐珠单抗治疗遗传性出血性毛细血管扩张症所致家族性鼻出血的疗效观察北大核心CSCD

目的： 观察贝伐珠单抗治疗遗传性出血性毛细血管扩张症（hereditary hemorrhagic telangiectasia,HHT）所致家族性鼻出血的临床效果。 方法： 回顾性分析2016年12月至2019年12月期间于北京安贞医院、解放军总医院第一医学中心和滨州医学院附属滨州市中心医院接受静脉滴注贝伐珠单抗治疗的27例HHT所致家族性鼻出血患者的相关资料,其中男性14例,女性13例,年龄（55.3±11.2）岁。按5 mg/kg体重计算贝伐珠单抗剂量,观察第一次用贝伐珠单抗治疗1个月后的疗效。用视觉模拟量表（VAS）对比治疗前后患者全身症状自我评分;用鼻出血严重程度量表（epistaxis severity score,ESS）对治疗前后患者的6个问题（鼻出血频率、持续时间、出血强度、治疗需求、是否贫血、是否输血）进行对比分析;对比治疗前后患者的血红蛋白水平变化情况。采用SPSS 20.0统计软件处理数据。 结果： 第一次贝伐珠单抗治疗1个月后,27例患者中22例自诉鼻出血严重程度明显改善,5例自诉治疗效果不显著,治疗有效率81.5%（22/27）。用药效果显著的22例患者疗效维持时间5～24个月,中位时间11.23个月。全身症状VAS评分较治疗前明显下降,差异有统计学意义［（2.41±2.55）分比（8.19±1.47）分,t=9.708,P<0.01］。ESS的6个问题的得分及ESS标准化评分较治疗前均明显下降［鼻出血频率（1.78±1.22）分比（3.44±0.80）分,t=6.814,P<0.01;出血持续时间（0.85±0.91）分比（3.00±0.73）分,t=8.845,P<0.01;出血强度（0.19±0.40）分比（1.00±0.00）分,t=10.696,P<0.01;治疗需求（0.22±0.42）分比（1.00±0.00）分,t=9.539,P<0.01;是否贫血（0.41±0.50）分比（0.89±0.32）分,t=4.914,P<0.01;是否输血（0.11±0.32）分比（0.41±0.50）分,t=3.309,P<0.01;ESS标准化评分（2.50±2.45）分比（7.60±1.30）分,t=9.344,P<0.01］。治疗后血红蛋白水平较治疗前明显提高,差异有统计学意义［（105.48±24.31） g/L比（73.07±23.71） g/L,t=6.864,P<0.01］。27例患者中HHT1型（ENG基因）8例,HHT2型（ACVRL1基因）19例;药物应用后鼻出血改善持续时间前者为（4.76±5.12）个月,后者为（7.60±10.84）个月,后者长于前者,但差异无统计学意义（P>0.05）。治疗前后ESS评分在两组基因型患者中的差异无统计学意义（P>0.05）。第一次用药治疗后2例女性患者出现停经,所有患者均未出现其他不良反应。 结论： 贝伐珠单抗静脉滴注治疗HHT所致家族性鼻出血疗效显著、安全性高。.;Objective: To observe the clinical effects of bevacizumab in the treatment of familial epistaxis caused by hereditary hemorrhagic telangiectasia (HHT). Methods: The data of 27 patients with familial epistaxis caused by HHT who were treated with bevacizumab intravenously from Beijing Anzhen Hospital, the First Clinical Center of Chinese People's Liberation Army General Hospital and Binzhou Central Hospital between December 2016 and December 2019 were retrospectively analyzed. There were 14 males and 13 females, aged (55.3±11.2) years. The dose of bevacizumab was calculated according to the body weight of 5 mg/kg. The curative effect was observed one month after the first treatment. Visual analogue scale (VAS) was used to compare patients' self-scores of systemic symptoms before and after treatment. Epistaxis severity score (ESS) was used to compare and analyze the six problems (including the frequency, duration, intensity, treatment demand, anemia and blood transfusion) of the patients before and after treatment. The changes of hemoglobin levels before and after treatment were compared. SPSS 20.0 statistical software was used to process the data. Results: Among the 27 patients at one month after the first bevacizumab treatment, 22 cases reported that the severity of epistaxis was improved significantly, and 5 cases reported that the treatment effect was not significant. The effective rate was 81.5% (22/27). The significant effect in 22 patients lasted for 5-24 months, with a median duration of 11.23 months. The VAS score of systemic symptoms decreased significantly compared with that before treatment (2.41±2.55 vs 8.19±1.47, t=9.708, P<0.01). The scores of six aspects and standardized scores of ESS were significantly decreased after treatment (epistaxis frequency: 1.78±1.22 vs 3.44±0.80, t=6.814, P<0.01;epistaxis duration: 0.85±0.91 vs 3.00±0.73, t=8.845, P<0.01;epistaxis intensity: 0.19±0.40 vs 1.00±0.00, t=10.696, P<0.01;treatment demand: 0.22 ± 0.42 vs 1.00±0.00, t=9.539, P<0.01;anemia: 0.41±0.50 vs 0.89±0.32, t=4.914, P<0.01;blood transfusion: 0.11±0.32 vs 0.41±0.50, t=3.309, P<0.01;ESS standardized score: 2.50±2.45 vs 7.60±1.30, t=9.344, P<0.01). The hemoglobin level after treatment was significantly higher than that before treatment ((105.48±24.31) g/L vs (73.07±23.71) g/L, t=6.864, P<0.01). Among the 27 patients, there were 8 cases of HHT1 (ENG gene) and 19 cases of HHT2 (ACVRL1 gene). The improvement duration of epistaxis in group HHT1 and group HHT2 was (4.76±5.12) months and (7.60±10.84) months, respectively, which was in group HHT2 longer than that of group HHT1, but there was no significant difference between the two groups (P>0.05). There was no significant difference in ESS scores between the two groups before and after treatment (P>0.05). Two female patients had amenorrhea after the first medication. All patients had no other adverse reactions and complications. Conclusion: Intravenous bevacizumab is significantly effective and safe in the treatment of familial epistaxis caused by HHT.

Effects of bevacizumab on familial epistaxis caused by hereditary hemorrhagic telangiectasia