恩替加干扰对HBeAg阳性多中心随机对照试验

StephenW

Adding peginterferon to entecavir for HBeAg-positive chronic hepatitis B: A multicentre randomized trial (ARES study)

• Willem Pieter Brouwer1,
• Qing Xie2,
• Milan Johan Sonneveld1,
• Ningping Zhang3,
• Qing Zhang4,
• Fehmi Tabak5,
• Anca Streinu6,
• Ji-Yao Wang3,
• Ramazan Idilman7,
• Hendrik Reesink8,
• Mircea Diculescu9,
• Krzysztof Simon10,
• Mihai Voiculescu11,
• Meral Akdogan12,
• Wlodzimierz Mazur13,
• Jurrien Reijnders1,
• Elke Verhey1,
• Bettina Hansen1,14,
• Harry L.A. Janssen1,15,* and
• for the ARES study group
  

DOI: 10.1002/hep.27586

Copyright © 2014 American Association for the Study of Liver Diseases

AbstractEntecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long-term therapy may be required. We investigated whether adding-on peginterferon (PEG-IFN) to ETV therapy enhances serologic response rates. In this global investigator-initiated, open-label, multicentre randomized trial, HBeAg-positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5mg/day) and were randomized in a 1:1 ratio to either PEG-IFN add-on therapy (180µg/week) from week 24 to 48 (n=85), or to continue ETV monotherapy (n=90). Response was defined as HBeAg loss with HBV DNA <200 IU/mL at week 48. Responders discontinued ETV at week 72. All patients were followed until week 96. Response was achieved in 16/85 (19%) patients allocated to the add-on arm versus 9/90 (10%) in the monotherapy arm (p=0.095). Adjusted for HBV DNA levels prior to randomized therapy, PEG-IFN add-on was significantly associated with response (OR 4.8, 95%CI: 1.6 – 14.0, p=0.004). Eleven (13%) of add-on treated patients achieved disease remission after ETV cessation, versus 2/90 (2%) of patients treated with monotherapy (p=0.007), which was 79% (11/14) versus 25% (2/8) of those who discontinued ETV (p=0.014). At week 96, 22 (26%) patients assigned add-on versus 12 (13%) assigned monotherapy achieved HBeAg seroconversion (p=0.036). PEG-IFN add-on led to significantly more decline in HBsAg, HBeAg and HBV DNA (all p<0.001). Combination therapy was well-tolerated. Conclusion: Although the primary endpoint was not reached, 24 weeks of PEG-IFN add-on therapy led to a higher proportion of HBeAg response compared to ETV monotherapy. Add-on therapy resulted in more viral decline and appeared to prevent relapse after stopping ETV. Hence PEG-IFN add-on therapy may facilitate the discontinuation of nucleos(t)ide analogues. http://www.Clinicaltrials.gov number: NCT00877760. (Hepatology 2014;)

StephenW

加入聚乙二醇干扰素恩替卡韦对HBeAg阳性慢性乙型肝炎的多中心随机对照试验（ARES研究）

    威廉·彼得·Brouwer1，
    清Xie2，
    米兰约翰Sonneveld1，
    Ningping Zhang3，
    清Zhang4，
    费赫米Tabak5，
    ANCA Streinu6，
    吉尧Wang3，
    拉马赞Idilman7，
    亨德里克Reesink8，
    米尔恰Diculescu9，
    克日什托夫·Simon10，
    米哈伊Voiculescu11，
    梅拉Akdogan12，
    沃齐米日Mazur13，
    Jurrien Reijnders1，
    埃尔克Verhey1，
    贝蒂娜Hansen1,14，
    哈利L.A。Janssen1,15，*和
    为ARES研究组

DOI：10.1002/ hep.27586




恩替卡韦（ETV）是乙型肝炎病毒复制的有效抑制剂，但长期治疗可能是必需的。我们调查是否增加，对聚乙二醇干扰素（PEG-IFN），以恩替卡韦治疗提高了血清学应答率。在这个全球研究者发起的，开放标签，多中心随机试验中，HBeAg阳性慢性乙型肝炎（CHB）患者的代偿性肝脏疾病开始单用恩替卡韦（0.5毫克/天），并随机在1：1的比例或者PEG-IFN24周添加治疗（每次180μg/周）至48（N=85），或继续ETV单药治疗（N=90）。反应定义为HBeAg消失与HBV DNA<200 IU/ mL的在48周停药反应者ETV在72周所有患者均随访至96周的响应是在八十五分之十六（19％）患者分配到添加 - 实现手臂与九十〇分之九（10％）的单药治疗组（P=0.095）。前随机治疗调整HBV DNA水平，PEG-IFN附加了显著与反应有关（OR4.8，95％CI：1.6 - 14.0，P = 0.004）。附加的治疗的患者的十（13％）达到疾病的缓解ETV停止后，相对于九十○分之二患者（2％）处理与单一疗法（p值=0.007），这是79％（11/14）与25％（ 2/8）那些谁停止ETV（P=0.014）的。在96周，22（26％）分配附加与12（13％）分配实现单药治疗的HBeAg血清学转换（P=0.036）的患者。 PEG-IFN插件导致的HBsAg，HBeAg和HBV DNA（均P<0.001）显著更加下降。联合治疗耐受性良好。结论：尽管初级端点没有达到，PEG-IFN24周添加治疗导致更高比例的HBeAg响应相比，ETV单药治疗。添加治疗导致更多的病毒性下降，出现了以预防复发ETV停止后。因此，PEG-IFN添加治疗可以促进核苷（酸）类似物停药。 http://www.Clinicaltrials.gov号：NCT00877760。 （2014年肝病;）

hao2014

太乱了
文章中添加干扰素实现恩替停药可能性多大啊？