Title聚乙二醇干扰素α-2b(Y型,40kD)注射液治疗HBeAg阳性慢性乙型肝炎患者的疗效和安全性分析
Other TitlesClinical effect and safety of pegylated interferon-α-2b injection (Y shape, 40 kD) in treatment of HBeAg-positive chronic hepatitis B patients
Authors侯凤琴
尹亚琳
曾玲英
尚佳
龚国忠
潘晨
张明香
尹炽标
谢青
彭雁忠
陈士俊
毛青
陈永平
毛乾国
张大志
韩涛
汪茂荣
赵伟
刘家俊
韩英
赵龙凤
罗光汉
张继明
彭劼
谭德明
李智伟
唐红
王豪
张跃新
李军
张伦理
陈良
贾继东
陈成伟
甄真
李保森
牛俊奇
孟庆华
袁宏
孙永涛
李树臣
盛吉芳
成军
孙黎
王贵强
Affiliation100034,北京大学第一医院感染疾病科
361028,厦门特宝生物工程股份有限公司
河南省人民医院, 郑州,450003
中南大学湘雅二医院, 长沙,410011
350025,福州市传染病医院
110006,沈阳市第六人民医院
510060,广州市第八人民医院
200025,上海交通大学医学院附属瑞金医院
北京大学深圳医院, 深圳,518036
250021,济南市传染病院
解放军第三军医大学第一附属医院, 重庆,400038
325000,温州医科大学附属第一医院
361001,厦门市中医院
400010,重庆医科大学附属第二医院
300170,天津市第三中心医院
中国人民解放军第八一医院, 南京,210002
210003,南京市第二医院
361003,厦门大学附属第一医院
第四军医大学西京医院, 西安,710032
山西医科大学第一医院, 太原,030001
广西医科大学第一附属医院, 南宁,530021
200040,复旦大学附属华山医院
南方医科大学南方医院, 广州,510510
中南大学湘雅医院, 长沙,410008
中国医科大学附属盛京医院, 沈阳,110022
四川大学华西医院, 成都,610041
100044,北京大学人民医院
830054,新疆医科大学第一附属医院
210029,江苏省人民医院
360102,南昌大学第一附属医院
201508,上海市公共卫生临床中心
100050,首都医科大学附属北京友谊医院
中国人民解放军第八五医院, 上海,200052
河北医科大学第三医院, 石家庄,050051
中国人民解放军第三○二医院, 北京,100039
吉林大学白求恩第一医院, 长春,130062
100069,首都医科大学附属北京佑安医院
730000,兰州大学第一医院
第四军医大学唐都医院, 西安,710038
150001,哈尔滨医科大学附属第二医院
310003,浙江大学医学院附属第一医院
100015,首都医科大学附属北京地坛医院
Keywords肝炎,乙型,慢性
聚乙二醇干扰素
HBeAg血清学转换率
临床试验
Hepatitis B,chronic
Peginterferon
HBeAg seroconversion
Clinical trial
Issue Date2017
Publisher中华肝脏病杂志
Citation中华肝脏病杂志. 2017, 25(8), 589-596.
Abstract目的 以标准剂量聚乙二醇干扰素α-2a (Peg-IFN α-2a)作为阳性药对照,评价长效干扰素Peg-IFN α-2b(Y型,40 kD)注射液(180μg/周)治疗HBeAg阳性慢性乙型肝炎(CHB)患者的疗效和安全性. 方法 多中心、随机开放、阳性药平行对照的Ⅲ期临床试验.筛选合格的HBeAg阳性CHB患者按照2∶1随机分配到Peg-IFN α-2b(Y型,40kD)组(试验组)和Peg-IFN α-2a组(对照组),治疗48周,停药随访24周.在筛选、基线、12周、24周、48周,60周和72周时保留受试者血浆用于中心化检测,用COBAS(R) Ampliprep/COBAS(R) TaqMan(R)HBV Test,Version 2.0荧光定量PCR检测HBV DNA定量,用Elecsys试剂盒电化学发光免疫分析法检测HBV标志物(HBsAg、抗-HBs、HBeAg、抗-HBe).详细记录不良事件.主要疗效指标为治疗48周随访24周后的HBeAg血清学转换率,并进行非劣效检验.计算两组治疗后HBeAg血清转换率差值(试验组-对照组)及其双侧95%可信区间(CI),当95%CI的下限大于-10%时,非劣效结论成立.根据不同的数据类型及特点分别采用t检验、x2检验、秩和检验等. 结果 入组HBeAg阳性CHB患者855例,实际治疗820例(试验组538例,对照组282例).全分析集数据显示,试验组和对照组的72周HBeAg血清学转换率分别为27.32%和22.70%,率差为4.63%,95% CI:-1.54% ~ 10.80%,P=0.149 3.符合方案分析集数据显示,试验组与对照组的HBeAg血清学转换率分别为30.75%和27.14%,率差为3.61%,95%CI:-3.87% ~ 11.09%,P=0.343 6.95% CI符合非劣效标准,试验组非劣效于对照组.试验组与对照组整体不良事件、严重不良事件及常见不良事件发生率均相似. 结论 Peg-IFN α治疗HBeAg阳性CHB患者的方案中,新药Peg-IFN α-2b(Y型,40kD)具有与对照药Peg-IFN α-2a相当的疗效和安全性.
Objective To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape,40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients,with standard-dose Peg-IFN-α-2a as positive control.Methods This study was a multicenter,randomized,open-label,and positive-controlled phase Ⅲ clinical trial.Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape,40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2∶1.The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal.Plasma samples were collected at screening,baseline,and 12,24,36,48,60,and 72 weeks for centralized detection.COBAS(R) Ampliprep/COBAS(R) TaqMan(R) HBV Test was used to measure HBV DNA level by quantitative real-time PCR.Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg,anti-HBs,HBeAg,anti-HBe).Adverse events were recorded in detail.The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up,and non-inferiority was also tested.The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated,and non-inferiority was demonstrated if the lower limit of 95% CI was >-10%.The t-test,chi-square test,or rank sum test was used according to the types and features of data.Results A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group).The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI-1.54% to 10.80%,P =0.1493).The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI-3.87% to 11.09%,P =0.3436).95% CI met the non-inferiority criteria,and the trial group was non-inferior to the control group.The two groups had similar incidence rates of adverse events,serious adverse events,and common adverse events.Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients,the new drug Peg-IFN-α-2b (Y shape,40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.
URIhttp://hdl.handle.net/20.500.11897/483418
ISSN1007-3418
DOI10.3760/cma.j.issn.1007-3418.2017.08.007
Appears in Collections:第一医院
深圳医院
人民医院

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