重组质粒-肝细胞生长因子基因治疗严重肢体缺血导致静息痛和溃疡Ⅱ期临床试验的长期随访研究  

Long-term follow-up of a phaseⅡclinical trial on pUDK-hepatocyte growth factor treatment for rest pain and ulcers caused by critical limb ischemia

作　　者：崔世军[1] 郭建明[1] 佟铸[1] 郭连瑞[1] 谷涌泉[1] Cui Shijun;Guo Jianming;Tong Zhu;Guo Lianrui;Gu Yongquan(Department of Vascular Surgery,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院血管外科,北京100053

出　　处：《药物不良反应杂志》2024年第4期193-197,共5页Adverse Drug Reactions Journal

摘　　要：目的探讨重组质粒-肝细胞生长因子(pUDK‑HGF)基因疗法治疗严重肢体缺血导致静息痛和溃疡的长期疗效和安全性。方法采用门诊和电话随访的方式对完成pUDK‑HGFⅡ期随机双盲安慰剂对照临床试验的患者进行长期随访,观察肿瘤的发生情况,并根据患者意愿进行肿瘤标志物检测、眼底检查、疼痛视觉模拟评分(VAS)和下肢CT血管造影(CTA)等。对观察结果进行描述性统计分析。结果共53例患者纳入分析,其中15例(28.3%)在Ⅱ期临床试验中为安慰剂组,38例(71.7%)为pUDK‑HGF治疗组,中位随访时间为2.8年,范围1.7~3.5年。随访期间,53例患者均未见肿瘤发生。pUDK‑HGF治疗组38例患者中18例接受了全面检查和评估,包括肿瘤标志物、眼底和CTA检查,静息痛患者接受了VAS评价。除1例发生一过性癌胚抗原轻度升高外,其他17例患者的肿瘤标志物均正常;18例均未出现增殖性视网膜血管病变。5例静息痛患者Ⅱ期临床试验结束(出组)时3例有效,2例无效;随访结束时CTA评价4例有效,1例无效;VAS评价5例均有效。13例溃疡患者出组时9例有效,4例无效;随访结束时,CTA评价10例有效,3例无效。结论pUDK‑HGF治疗严重肢体缺血导致的静息痛和溃疡比较安全,未发现致癌和导致增殖性视网膜血管病变的风险,长期疗效满意。Objective To explore the long-term efficacy and safety of gene therapy with pUDKhepatocyte growth factor(pUDK-HGF)for rest pain and ulcers caused by critical limb ischemia.Methods Long-term follow-up were conducted through outpatient and telephone on patients who completed the pUDK-HGF PhaseⅡrandomized double-blind placebo-controlled trial.The occurrence of tumors was observed,and tumor markers detection,fundus examination,visual analogue scale(VAS),and lower limb CT angiography(CTA)were performed according to voluntary principle.The results were analyzed descriptively and statistically.Results A total of 53 patients were included in the analysis,of which 15(28.3%)were in the placebo group and 38(71.7%)were in the pUDK-HGF treatment group in the Phase Ⅱ clinical trial.The median follow-up time was 2.8 years,ranging from 1.7 to 3.5 years.During the follow-up period,no tumor was found in the 53 patients.Among the 38 patients in the pUDK-HGF treatment group,18 underwent comprehensive examination and evaluation,including tumor markers,fundus and CTA examination,and patients with resting pain underwent VAS evaluation.Among them,1 patient had transient mild elevation of carcinoembryonic antigen,and no abnormal tumor markers were found in the other 17 patients;no proliferative retinal vasculopathy was found in the fundus examination.At the end of the phase Ⅱ clinical trial(out-group),3 were effective and 2 were ineffective of the 5 patients with rest pain;at the end of this follow-up period,4 were evaluated as effectiveness and 1 as ineffectiveness according to CTA,and 5 were all evaluated as effectiveness according to VAS.Of the 13 patients with ulcer,9 were evaluated as effectiveness and 4 were as ineffectiveness according to CTA at out-group;10 were evaluated as effectiveness and 3 were as ineffectiveness at the end of this follow-up.Conclusions pUDK-HGF had relatively good safety in the treatment of rest pain and ulcers caused by critical limb ischemia.No risk of carcinogenesis and proliferative retinal vascul

关 键 词：外周动脉疾病 严重肢体缺血 基因治疗 重组质粒-肝细胞生长因子 临床试验 Ⅱ期 长期随访 

分 类 号：R654.4[医药卫生—外科学]