血源性人凝血因子Ⅷ治疗血友病A患者的有效性及安全性评价

Efficacy and safety evaluation of plasma-derived human coagulation factor VIl in patients with hemophilia A

目的评价血浆源性人凝血因子Ⅷ(coagulation factorⅧ,FⅧ)在治疗血友病A患者中的有效性及安全性。方法本文采用多中心、单臂、开放性设计开展Ⅲ临床试验,5家研究中心共入组54例患者,根据受试者体重、病情严重程度等因素计算FⅧ输注量,计算首次输注后10 min FⅧ活性输注效率值作为主要疗效指标,首次输注后24 h内对受试者出血症状与体征改善作为次要疗效指标进行有效性评分。通过记录不良事件,在治疗后d90及d180检测病原微生物指标及凝血因子Ⅷ抑制物来进行安全性评价。结果54名受试者首次输注后10 min的FⅧ活性输注效率均值为171.9%,中位数为169.5%,均高于设定的目标值100%。首次输注后24 h内对受试者出血症状与体征改善进行评分,其中“显效”19例(35.2%),“良效”35例(64.8%),临床总有效率达到100%。5名(9.3%)受试者发生6例次与药物相关的不良反应。治疗后d90、d180检测乙型肝炎表面抗原、丙型肝炎抗体、HlV抗体、梅毒螺旋体抗体、凝血因子Ⅷ抑制物,未发现阴性转阳性病例。结论该FⅧ制剂,输注后能在短期内显著提高血友病A患者的FⅧ活性水平、输注效率高,能达到较好治疗水平,并能有效控制和缓解出血症状和体征,总体安全性良好。

Objective To evaluate the efficacy and safety of plasma-derived human coagulation factor Ⅷ(F Ⅷ)in the treatment of patients with hemophilia A.Methods A multi-center and open,SAT(single-arm trials)clinical study was conducted.A total of 54 subjects with hemophilia A were enrolled in 5 research centers.FVI was injected according to the subjects'weight,severity of disease and other factors,and the transfusion efficiency of FⅧ activity at 10 min after the first infusion of the first bleeding event was taken as the main efficacy indexes.The improvement scores of bleeding symptoms and signs within 24 h after the first infusion of the first bleeding event were the secondary efficacy indexes.The pathogenic microbial indexes and FⅧ inhibitors were detected on 90(th)and 180(th)day after treatment.Results The transfusion efficiency of FⅧ activity of 54 subjects at 10 min after the first infusion was 171.9%on average,with median of 169.5%,both higher than the target value of 100%.Within 24 h after the first infusion,the improvement of bleeding symptoms and signs of the subjects were scored,among which 19 cases(35.2%)were“obvious",35 cases(64.8%)were"good",and the total clinical effective rate reached 100%.Five subjects(9.3%)had six drug-related adverse events.On 90(th)and 180(th)day after treatment,hepatitis B surface antigen,hepatitis C antibody,HIV antibody,treponema pallidum antibody and FⅧ inhibitors were detected,and no negative to positive cases were found.ConclusionAfter infusion,the FⅧ preparation can significantly improve the FⅧ activity level in hemophilia A patients in a short period of time,which has high infusion efficiency and can achieve better treatmen efficacy,and can also effectively control and relieve bleeding symptoms and signs,with good overall safety.