在初治和经治丙型肝炎病毒基因1b型慢性感染的非肝硬化亚洲成年患者中评价奥比帕利联合达塞布韦治疗的有效性和安全性：随机、双盲、安慰剂对照研究  

Efficacy and safety of paritaprevir/ritonavir/ombitasvir combined with dasabuvir in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype lb infection： a randomized, double-blind, placebo-controlled study - China data

作　　者：魏来[1] 成军[2] Luo Yan 李军[4] 段钟平[5] 侯金林[6] 贾继东[7] 张明香[8] 黄燕[9] 谢青[10] 王贵强[11] 杨东亮[12] 赵伟[13] 赵彩彦[14] 唐红[15] 蔺淑梅[16] 龚国忠[17] 牛俊奇[18] 高志良[19] Sarah Kopecky-Bromberg Linch Fredrick Niloufar Mobashery Wang Ye 王介非[21] Wei Lai;Cheng Jun;Luo Yan;Li Jun;Duan Zhongping;Hou Jinlin;Jia Jidong;Zhang Mingxiang;Huang Yan;Xie Qing;Wang Guiqiang;}rang Dongliang;Zhao Wei;Zhao Caiyan;Tang Hong;Lin Shumei;Gong Guozhong;Niu Junqi;Gao Zhiliang;Sarah Kopecky-Bromberg;Linda Fredrick;Niloufar Mobashery;Wang Ye;Wang Jiefei(Peking University People＇s Hospital, Beijing 100044, China;Beijing Ditan Hospital Capital Medical University, Beijing 100015, Chin;AbbVie lnc., North Chicago 60064, IL, US;Jiangsu Province Hospital, Nanjing 210029, Chin;Beijing You＇an Hospital Capital Medical University, Beijing 100069, Chin;Nan Fang Hospital Guangzhou 510515, Chin;Beijing Friendship Hospital Capital Medical University, Beijing 100050, Chin;Shenyang 6th People＇s Hospital, Shenyang 110006, Chin;Xiangya Hospital Central South University, Changsha 410008, Chin;ui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, Chin;eking University First Hospital, Beijing 100034, Chin;nion Hospital Tongji Mecical College, Huazhong University of Science and Technology, Wuhan 430022, Chin;anjing 2nd Hospital, Nanjing 210028, Chin;he 3rd Hospital of Hebei Medical University, Shijiazhuang 500000, Chin;est China School of Medicine, Chengdu 610041, Chin;he 1st Hospital of Xi＇an Jiaotong Univeersity, Xi＇an 710065, Chin;he 2nd Hospital of Central South University, Changsha 410011, Chin;he 1st Hospital of Jilin University, Changchun 130021, Chin;he 3rd Hospital, Sun Yay-sen Hospital, Guangzhou 510630, Chin;AbbVie. China. Shanghai 200041, China;hanghai Public Health Clinical Center, Shanghai 201508, Chin)

机构地区：[1]北京大学人民医院,100044 [2]首都医科大学附属北京地坛医院,北京100015 [3]AbbVie Inc., North Chicago, IL, USA, Chicago 60064 [4]江苏省人民医院,南京210029 [5]首都医科大学附属佑安医院,北京100069 [6]南方医科大学南方医院,广州510515 [7]首都医科大学附属北京友谊医院,北京100050 [8]沈阳市第六人民医院,110006 [9]中南大学湘雅医院,长沙410008 [10]上海交通大学医学院附属瑞金医院,200025 [11]北京大学第一医院,100034 [12]华中科技大学同济医学院附属协和医院,武汉430022 [13]南京市第二医院,210028 [14]河北医科大学第三医院,石家庄500000 [15]四川大学华西医院,成都610041 [16]西安交通大学第一附属医院,710065 [17]中南大学湘雅二院,长沙410011 [18]吉林大学第一医院,长春130021 [19]中山大学附属第三医院,广州510630 [20]AbbVie.China. Shanghai, Shanghai 200041 [21]上海市公共卫生临床中心,上海201508

出　　处：《中华肝脏病杂志》2018年第5期359-364,共6页Chinese Journal of Hepatology

摘　　要：目的 评估奥比帕利（奥比他韦/帕立瑞韦/利托那韦,OBV/PTV/r）25/150/100mg,1次/d,联合达塞布韦250mg,2次/d,在丙型肝炎病毒基因1b型感染的初治和经治非肝硬化中国成年患者中的有效性和安全性.方法 采用随机、双盲、安慰剂对照、多中心Ⅲ期临床试验,在中国大陆、韩国、中国台湾地区进行.纳入基因1b型初治和普通干扰素/聚乙二醇干扰素α联合利巴韦林经治非肝硬化患者,随机分为2组,分别接受OBV/PTV/r联合达塞布韦方案立即治疗12周（A组）,或接受安慰剂治疗12周后再继续接受OBV/PTV/r联合达塞布韦方案治疗12周（B组）.评估患者停药12周获得的持续病毒学应答（SVR12）及停药24周获得的持续病毒学应答（SVR24）率,及双盲阶段和开放标签阶段治疗后的不良事件和实验室异常发生率. 结果 共纳入410例中国大陆患者资料,按1∶1比例随机分至A组和B组（每组205例）.A组（205例）中初治患者的SVR12及SVR24率均为99％ （95％CI：94.8％ ～ 99.8％）,经治患者的SVR12及SVR24率均为100％ （95％ CI：96.3％～ 100％）,不同基线特征对SVR12及SVR24率没有影响.发生的大多数不良事件为轻度,治疗期间≥3级实验室异常少见,主要包括丙氨酸氨基转移酶升高（双盲阶段A组2例）、天冬氨酸氨基转移酶升高（双盲阶段A组3例）和总胆红素升高（开放标签阶段B组1例）,通常无症状,用药中断或停药后可恢复.仅有1例因不良事件停药（B组,开放标签阶段）. 结论 疗程为12周的OBV/PTV/r联合达塞布韦方案治疗中国基因1b型初治和经治非肝硬化慢性丙型肝炎患者可获得99％～ 100％的SVR12及SVR24率,且耐受性和安全性良好.Objective To evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir （OBV/PTV/r） 25/150/100 mg once daily combined with dasabuvir 250mg,twice daily in non-cirrhotic Chinese adult patients with newly diagnosed and treated chronic HCV genotype 1b infection.Methods A randomized,double-blind,placebo-controlled,multicenter phase 3 clinical trial was conducted in China's Mainland,Korea,and Taiwan.Safety and efficacy of OBV/PTV/r plus DSV administered for 12 weeks were evaluated in a newly diagnosed and treated （interferon alpha/pegylated interferon alpha） and ribavirin non-cirrhotic adults with chronic HCVgenotype 1b infection.Patients randomly received OBV/PTV/r plus DSV for 12 weeks （Group A）,or placebo for 12 weeks （Group B） followed by an open-label phase of OBV/PTV/r plus DSV for 12 weeks.Sustained response （SVR12） rate obtained at 12 weeks and （SVR24） 24 weeks after discontinuation of treatment,and the incidence of adverse events and laboratory abnormalities after double-blind and open-label phase treatment were assessed.Results A total of 410 cases of Chinese patients were included and randomly assigned to group A and B （with 205 cases in each group） in a 1∶1 ratio.The rates of SVR12 and SVR24 were 99% （95% CI：94.8%-99.8%） in the newly diagnosed patients in group A （205 patients） and the rates of SVR12 and SVR24 were 100% in treated patients （95% CI：96.3%-100%）.Different baseline characteristics had no effect on SVR12 and SVR24 rates.Most of the adverse events occurred were mild,asymptomatic,and ≥ 3 laboratory abnormalities during treatment were rare,including elevation of alanine aminotransferase （2 cases in double-blind stage A group）,aspartate aminotransferase （Double-blind stage A （3 cases） and total bilirubin （1 case in open-label phase B group）;however,those mild adverse events could be recovered after drug withdrawal or discontinuation.onlyl person discontinued drugs due to adverse events （Group B,open-label phase）.Conclusion

关 键 词：肝炎 丙型 慢性 直接抗病毒药物 安全性 

分 类 号：R512.63[医药卫生—内科学]