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标题: 干扰素和恩替卡韦联合的临床试验结果 [打印本页]

作者: 肝胆速递    时间: 2012-8-23 06:59     标题: 干扰素和恩替卡韦联合的临床试验结果

本帖最后由 肝胆速递 于 2012-8-24 23:07 编辑

PegInterferon + Entecavir - Results from a global trial
干扰素和恩替卡韦联合的临床试验结果

肝胆速递:有助于HBe转阴及HBsAg清除

Nederlandse Vereniging voor Hepatologie (klinisch)

ADDING PEGINTERFERON ALFA-2A TO ENTECAVIR INCREASES HBSAG DECLINE AND HBEAG CLEARANCE – FIRST RESULTS FROM A GLOBAL RANDOMIZED TRIAL (ARES STUDY)

M.J. Sonneveld1, Q. Xie2, N.P. Zhang3, Q. Zhang4, F. Tabak5, A. Streinu6, J.-Y. Wang3, R. Idilman7, A. de Niet8, M. Diculescu9, A.J. van Vuuren1, E. Verhey1, B.E. Hansen1,10, H.L.A. Janssen1


Departments of 1Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands; 2Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China; 3Gastroenterology and Hepatology, Zhong Shan Hospital, Fu Dan University, Shanghai, China; 4Gastroenterology and Hepatology, Shanghai Public Health Center, Fu Dan University, Shanghai, China; 5Department of Infectious Diseases, Cerrahpasa Medical School, Istanbul, Turkey; 6National Institute of Infectious Disease, Bucharest, Romania; 7Gastroenterology and Hepatology, University of Ankara, Ankara, Turkey; 8Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands; 9Gastroenterology, Fundeni Cinical Institute, Bucharest, Romania; 10Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands;

Email:
[email protected]
[email protected], [email protected]
[email protected]
[email protected], [email protected]
[email protected], [email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]


Background & aims. Entecavir (ETV) is a potent inhibitor of viral replication in HBeAg-positive chronic hepatitis B (CHB) patients, but serological response is infrequently achieved and indefinite therapy should therefore be anticipated in the majority of patients. Addition of peginterferon (PEG-IFN) to ETV may increase serological response rates.
Methods. In this investigator-initiated randomized controlled trial 184 HBeAg-positive patients with compensated liver disease were enrolled at 15 sites in Europe and China and allocated to either ETV 0.5mg daily alone for 48 weeks or a 24 week addition of PEG-IFN alfa-2a 180 ug weekly after 24 weeks of ETV monotherapy. Response (HBeAg loss with HBV DNA <200 IU/mL) was assessed at week 48, and responders were allowed to discontinue treatment after 24 weeks consolidation treatment (week 72), with subsequent off-treatment follow-up until week 96. Results at week 48 are presented here.
Results. 177 patients received at least one dose of allocated treatment, 93 ETV alone and 84 ETV with PEG-IFN add-on. Sixty-one percent of patients were of Asian ethnicity and all major HBV genotypes were present (A/B/C/D in 7/19/42/32%). A total of 160 patients had reached week 48 by June 2012, and the remaining patients will do so within 2 months. Patients were comparable with regard to important baseline characteristics, except for HBsAg which was higher in patients receiving combination therapy (4.28 versus 4.03 log IU/mL, p=0.05).  Response, as well as HBeAg loss alone, was achieved in 18% of patients who received PEG-IFN add-on, compared to 8% of patients treated with ETV alone (p=0.07). PEG-IFN add-on resulted in more decline of HBV DNA (6.33 versus 5.91 log IU/mL, p=0.05), HBeAg (1.99 versus 1.56 log IU/mL, p=0.01) and HBsAg (0.84 versus 0.32 log IU/mL, p<0.001) at week 48. Only one patient (who received PEG-IFN add-on) had clearance of HBsAg at week 48. After adjustment for the differences in baseline HBsAg levels, addition of PEG-IFN was independently associated with response at week 48 (adjusted odds ratio: 3.63, 95% CI: 1.24 – 10.7, p=0.01). Add-on PEG-IFN was well-tolerated and no relevant safety concerns were raised.
Conclusion. A 24 week add-on of PEG-IFN treatment increases HBsAg decline and clearance of HBeAg and may therefore improve the chances of finite treatment in HBeAg-positive CHB patients treated with ETV.









作者: 肝胆速递    时间: 2012-8-23 07:00

加入聚乙二醇干扰素α-2a干扰素恩替卡韦增加乙型肝炎表面抗原下降和HBeAg清除 - 从全球的随机对照试验(ARES研究的第一个成果)

兆焦耳Sonneveld1,Q. Xie2,N.P.; Zhang3,问:Zhang4,F. Tabak5,A. Streinu6,J.-Y. Wang3,R. Idilman7次,M. Diculescu9 A.去Niet8,AJ面包车Vuuren1,E. Verhey1,B.E. hansen1,10,H.L.A. Janssen1


部门的1Gastroenterology,荷兰鹿特丹Erasmus MC大学医学中心; 2Infectious疾病,中国,上海交通大学医学院附属瑞金医院,3Gastroenterology和肝病,中山医院,复旦大学,上海,中国; 4Gastroenterology和肝病学和肝病学杂志,上海公共卫生中心,复旦大学,上海,中国传染病的5Department的,Cerrahpasa医学院,伊斯坦布尔,土耳其; 6National传染病研究所,布加勒斯特,罗马尼亚; 7Gastroenterology和肝病,安卡拉大学,安卡拉,土耳其,8Gastroenterology肝脏病学,学术医学中心,荷兰阿姆斯特丹,9Gastroenterology,Fundeni Cinical研究所,布加勒斯特,罗马尼亚,10Public卫生,Erasmus MC大学医学中心,鹿特丹,荷兰;

电子邮件地址:
m.j.sonneveld @ erasmusmc.nl
[email protected][email protected]
zhang.ningping @ ZS-hospital.sh.cn
[email protected][email protected]
[email protected][email protected]
[email protected]
wang.jiyao @ ZS-hospital.sh.cn
[email protected]
a.deniet @ amc.uva.nl
[email protected]
e.verhey @ erasmusmc.nl
a.vanvuuren @ erasmusmc.nl
b.hansen @ erasmusmc.nl
h.janssen @ erasmusmc.nl


背景及目的。在HBeAg阳性慢性乙型肝炎(CHB)患者,恩替卡韦(ETV)是一种强效抑制病毒的复制,但很少实现,不确定的治疗,因此,预计在广大患者的血清学反应。添加聚乙二醇干扰素(PEG-IFN)ETV可能会增加血清学反应率。
方法。研究者发起的随机对照试验,184例HBeAg阳性患者的代偿性肝脏疾病患者在欧洲和中国的15个站点,为48周或24周的另外的PEG-IFNα-2a干扰素为ETV 0.5毫克每天单独分配ETV单药治疗24周后每周180微克。 48周时应答(HBeAg消失,HBV DNA <200 IU /毫升)进行了评估和响应者被允许停止治疗,巩固治疗后24周(第72周),随后后续的处理,直到96周。结果在第48周。
结果。 177例患者接受至少一剂分配的治疗,93 ETV PEG-IFN单独和84 ETV添加的。 61%的患者为亚洲人种,所有主要的HBV基因型(A / B / C / D 7/19/42/32%)。 2012年6月,共有160名患者已经达到48周,其余患者2个月内将这样做。患者与重要的基线特征方面,除了对HBsAg为高在接受联合治疗的患者(4.28比4.03日志IU / mL的电话号码= 0.05)。反应,以及作为单独HBeAg消失,18%的患者接受PEG-IFN添加,取得了8%,仅恩替卡韦治疗的患者(P = 0.07)。 PEG-IFN添加的上导致更多的HBV DNA下降(6.33比5.91日志IU / mL时,P = 0.05)(1.99与1.56日志IU / mL时,P = 0.01),乙型肝炎e抗原和乙肝表面抗原(0.84比0.32日志IU /毫升,P <0.001),在第48周。只有一个病人(PEG-IFN附加)在48周时乙肝表面抗原清除。调整后基线HBsAg水平的差异,此外,PEG-IFN独立与反应在第48周(调整后的比值比:3.63,95%CI:1.24  -  10.7,P = 0.01)。 PEG-IFN的耐受性良好,并没有相关的安全问题提出了。
结论。 A 24周增加,增加对PEG-IFN治疗的HBeAg HBsAg的下降和清除,因此可能提高的机会有限恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者的治疗。
作者: StephenW    时间: 2012-8-23 08:44

本帖最后由 StephenW 于 2012-8-23 08:45 编辑

这治疗方法结果不同于日本的研究结果。
作者: rocgao    时间: 2012-8-23 09:15

日本实验是贯续疗法,这个实验是在etv服用24周时+INF联合治疗。治疗方法有差异。
作者: kennyu    时间: 2012-8-23 18:22

回复 肝胆速递 的帖子

没给出HBsAg的清除率?
作者: StephenW    时间: 2012-8-23 18:30

回复 kennyu 的帖子

Only one patient (who received PEG-IFN add-on) had clearance of HBsAg at week 48
只有一个病人(PEG-IFN附加)48周时乙肝表面抗原清除.


作者: 咬牙硬挺    时间: 2012-8-25 07:14

回复 StephenW 的帖子

好几天没见你发帖了,正担心你离开论坛了,见到你很开心哈
作者: wzu    时间: 2012-8-25 11:51

我水平低!中英文都看不懂!!
作者: wzu    时间: 2012-8-25 11:53

谁给我好好翻译一下!?我儿子正再用干扰素(短效)联合恩替卡韦治疗。不知道效果如何?
作者: MP4    时间: 2012-8-25 14:38

肝胆速递=StephenW?




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