EASL2015:一个随机前瞻性开放标签试验比较聚乙二醇干扰素+阿

StephenW

CT-4251
Clinical Trials in Progess
A RANDOMISED PROSPECTIVE OPEN-LABEL TRIAL COMPARING PEGINTERFERON + ADEFOVIR AND
PEGINTERFERON + TENOFOVIR VERSUS NO TREATMENT IN HBEAG NEGATIVE CHRONIC HEPATITIS B
PATIENTS WITH LOW VIRAL LOAD: INTERIM ANALYSIS OF WEEK 48 RESULTS
Annikki de Niet* 1, Louis Jansen1, Femke Stelma1, Sophie B. Willemse1, Sjoerd D. Kuiken2, Sebastiaan Weijer3, Karin M.
van Nieuwkerk4, Hans L. Zaaijer5, 6, Richard Molenkamp5, Robert B. Takkenberg1, Maarten Koot7, Joanne Verheij8, Ulrich
Beuers1, Hendrik W. Reesink1
1Gastroenterology and Hepatology, Academic Medical Centre, 2Gastroenterology and Hepatology, Sint Lucas Andreas
Hospital, Amsterdam, 3Internal Medicine, Medical Centre Zuiderzee, Lelystad, 4Gastroenterology and Hepatology, VU
Medical Centre, 5Medical Microbiology, Academic Medical Centre, 6Blood-borne Infections, 7Virus Diagnostic Services,
Sanquin, 8Pathology, Academic Medical Centre, Amsterdam, Netherlands
Corresponding author’s email: [email protected]
Do you want to apply for a Young Investigator Bursary?: No
Background and Aims: Chronic hepatitis B (CHB) patients with a low viral load (LVL) are currently not eligible for antiviral
treatment. However, they comprise the largest group of hepatitis B virus-infected patients and are still at risk to develop
cirrhosis or hepatocellular carcinoma. Here we present the week 48 results of a randomized trial comparing combination
treatment of peginterferon alfa-2a (Peg-IFN) and a nucleotide analogue versus no treatment for CHB patients with LVL.
Methods: 134 CHB patients (HBeAg-negative, HBV-DNA <20,000 IU/mL) were randomized 1:1:1 to receive Peg-
IFN+adefovir (arm I; n=46), Peg-IFN+tenofovir (arm II; n=45) or no treatment (arm III; n=43) for 48 weeks (ITT
population). Randomization was stratified by HBV genotype A (22%), non-A (B 7%, C 4%, D 26%, E/F/G 20%), or
indeterminate (21%). The median age was 43 years, 57% were male. Twelve patients discontinued the study before
week 48 (5 in arm I, 6 in arm II, 1 in arm III). HBsAg loss (AxSYM <0.05 IU/mL) and quantitative HBsAg level (Architect)
was determined at regular intervals, and were compared using Fisher’s, Mann-Whitney U or Wilcoxon test.
Results: At week 48, 4 patients receiving combination therapy had achieved HBsAg loss, compared to none of the
untreated patients (ITT 4.4% vs 0.0%, p=0.31). Patients with HBsAg loss were treated in arm I (n=1) and arm II (n=3),
and had HBV genotype A (n=1), B (n=1), or indeterminate (n=2). Baseline HBsAg levels were comparable between study
arms (median 3.34 log IU/mL ). In a per-protocol analysis, HBsAg level had declined significantly in all arms at week 48; -
0.33 (p<0.001), -0.22 (p<0.001), and -0.07 (p=0.02) median log reduction for arms I, II, and III, respectively. No difference
in HBsAg decline was observed between treatment arms. However, HBsAg declined more in treatment arms I (p<0.001)
and II (p=0.002) compared to the control arm III. A strong HBsAg decline of >1.0 log IU/mL was observed in 17 treated
patients (21%), but in none of the untreated patients (p<0.001). No unexpected adverse events were observed in the
treatment arms.
Conclusions: In CHB patients with a low viral load, 48 weeks of combination treatment with Peg-IFN and adefovir or
tenofovir resulted in 4.4% HBsAg loss, compared to 0.0% in the untreated control group. The significant decline in HBsAg
at week 48 may indicate a further increase in the rate of HBsAg loss during treatment-free follow-up. Week 72 results are
expected in March 2015.
Disclosure of Interest: A. de Niet: : None Declared, L. Jansen: : None Declared, F. Stelma: : None Declared, S.
Willemse: Sponsored Lectures (National or International): Gilead, Roche, BMS en Janssen, S. Kuiken: : None Declared,
S. Weijer: : None Declared, K. van Nieuwkerk: : None Declared, H. Zaaijer: : None Declared, R. Molenkamp: : None
Declared, R. Takkenberg: Consultant: Bristol Myers Squibb and Gilead Sciences, M. Koot: : None Declared, J. Verheij: :
None Declared, U. Beuers: : None Declared, H. Reesink: Grant: Bristol Myers Squibb, Gilead Sciences, Roche, Merck,
Replicor and Alnylam, Consultant: Bristol Myers Squibb, Gilead Sciences, Roche, Merck, Korean Green Cross, Replicor
and Alnylam

StephenW

CT-4251
在陆侃临床试验
一个随机前瞻性开放标签试验比较聚乙二醇干扰素+阿德福韦和
聚乙二醇干扰素+替诺福韦与不治疗HBeAg阴性慢性乙型肝炎
患者的病毒载量低：周48结果期中分析
Annikki德Niet的* 1，路易斯Jansen1，Femke Stelma1，苏菲B. Willemse1，Sjoerd D. Kuiken2，Sebastiaan Weijer3，卡琳M.
面包车Nieuwkerk4，汉斯·L. Zaaijer5，6，理查德·Molenkamp5，罗伯特·B·Takkenberg1，马腾Koot7，乔安妮Verheij8，乌尔里希
Beuers1，亨德里克·W·Reesink1
1Gastroenterology和肝病，学术医疗中心，2Gastroenterology和肝病，圣马丁卢卡斯安德烈亚斯
医院，阿姆斯特丹，3Internal医药，医疗中心德海，米德尔，4Gastroenterology和肝病，VU
医疗中心，5Medical微生物学，学术医疗中心，6Blood源性感染，7Virus诊断服务，
Sanquin，8Pathology，学术医疗中心，阿姆斯特丹，荷兰
通讯作者的邮箱：[email protected]
你想申请青年科学家奖学金？：否
背景和目的：慢性乙型肝炎（CHB）患者的病毒载量低（LVL）目前不符合抗病毒
治疗。然而，它们包括乙肝病毒感染患者的最大组和仍处于风险发展
肝硬化或肝细胞癌。在这里，我们提出了48周结果的随机试验对比组合
治疗聚乙二醇干扰素α-2a干扰素（PEG-IFN）和核苷类似物与不治疗的慢性乙肝患者的单板层积材。
方法：134 CHB患者（HBeAg阴性，HBV-DNA <20000 IU /毫升），随机1：1：1到接收PEG-
干扰素+阿德福韦（臂我; N = 46），聚乙二醇干扰素+替诺福韦（ARM II; N = 45）或不治疗（手臂III; N = 43），48周（ITT
人口）。随机进行分层HBV基因型A（22％），非A（B 7％，C 4％，D 26％，E / F / G 20％），或
不确定的（21％）。平均年龄为43岁，57％为男性。十二名病人停止了研究前
48周（在我手臂5，6臂II，1手臂III）。 HBsAg消失（AXSYM <0.05 IU / mL）和定量的HBsAg水平（建筑师）
是定期确定，并且采用Fisher，曼 - 惠特尼U或Wilcoxon检验进行比较。
结果：在48周，4例患者接受联合治疗取得了HBsAg消失，相比之下，没有一个
未经治疗的患者（ITT 4.4％比0.0％，p值= 0.31）。患者HBsAg消失在手臂治疗I（N = 1）和ARM II（N = 3），
并有HBV基因型A（N = 1），B（N = 1），或不确定（N = 2）。基线HBsAg水平是相当的研究之间
臂（中位数3.34日志IU /毫升）。在按方案分析，乙肝表面抗原水平已经在所有的武器在48周显著下降; -
0.33（P <0.001），-0.22 I，II和III，分别为（P <0.001），和-0.07（P = 0.02），平均对数减少武器。没有不同
在HBsAg的下降是治疗组之间变化。然而，更多的乙肝表面抗原在治疗组拒绝我（P <0.001）
和二（p值= 0.002）相比，控制臂三。中> 1.0强大的HBsAg下降登录IU / mL的患者中，17处理
例（21％），但在没有任何未经治疗的患者（P <0.001）的。不出意外的不良事件的观察
治疗武器。
结论：在慢性乙肝患者病毒载量低的48周联合治疗与聚乙二醇干扰素和阿德福韦或
替诺福韦导致4.4％HBsAg消失，而在未处理的对照组0.0％。在乙肝表面抗原的显著下降
在48周可指示在治疗期间无后续在HBsAg消失率的进一步增加。第72周的结果
预计在2015年三月。
股权变动：A.德Niet的：无申明，L.詹森：无申明，F Stelma：无申报，S。
WILLEMSE：赞助讲座（国内或国际）：Gilead公司，罗氏，拜耳恩扬森，S库伊肯：无申报，
S. Weijer：无申明，光面包车Nieuwkerk：无申明，H Zaaijer：无申明，R. Molenkamp研究：：无
声明R. Takkenberg：顾问：布里斯托尔Myers Squibb公司和Gilead Sciences公司，M寻根：无申明，J。Verheij：
无申明，美国Beuers：无申明，H Reesink：格兰特：布里斯托尔Myers Squibb公司，Gilead Sciences公司，罗氏，默克，
Replicor和Alnylam公司，顾问：布里斯托尔Myers Squibb公司，Gilead Sciences公司，罗氏，默克，韩国绿十字，Replicor
和Alnylam公司