NATAP/EASL 派罗欣乙肝结果/乙肝表面抗原

StephenW

> Subject: NATAP/EASL: Pegasys HBV Outcomes/HBsAg
>
> Efficacy and Safety of Peginterferon Alfa-2a (40KD) in HBeAg-Positive Chronic Hepatitis B Patients Participating in a Response-Guided Therapy Study: An Interim Analysis at Week 72


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> Reported by Jules Levin
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> EASL 2013 April 24-28 Amsterdam
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>  
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> J. Hou,1 H. Ma,2 J. Sun,1 Q. Xie,3 Y. Xie,4 Y. Sun,5 H. Wang,6 G. Shi,7 M. Wan,8 J. Niu,9 Q. Ning,10 Y. Yu,11 Y. Zhao12
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> 1Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China; 2Liver Research Center, Beijing Friendship Hospital, Beijing, China; 3Department of Infectious Disease, Shanghai Ruijin Hospital, Shanghai, China; 4Liver Disease Department, Beijing DiTan Hospital, Beijing, China; 5Department of Infectious Disease, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China; 6Liver Disease Department, Peking University People’s Hospital, Beijing, China; 7Department of Infectious Disease, Huashan Hospital affiliated to Fudan University, Shanghai, China; 8Department of Infectious Disease, Shanghai Changhi Hospital, Shanghai, China; 9Department of Liver, First Hospital of Jilin University, Changchun, China; 10Department of Infectious Disease, Wuhan Tongji Hospital affiliated to Huazhong Technology University, Tongji Medical College, Wuhan, China; 11Department of Infectious Disease, Peking University First Hospital, Beijing, China; 12Shanghai Roche Pharmaceuticals Co. Ltd, Shanghai, China
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>
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> Introduction
> For patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB), HBeAg loss or seroconversion after discontinuation of peginterferon therapy is associated with increased chance of subsequent hepatitis B surface antigen (HBsAg) loss,[1] and improved long-term clinical outcomes.[2]
> Early on-treatment HBsAg decline is associated with sustained immune control post-treatment.
> – In a previous retrospective analysis that assessed the value of on-treatment HBsAg quantification in identifying patients likely to achieve a sustained response, it was found that 54% of patients with HBsAg <1500 IU/mL at Week 24 achieved HBeAg seroconversion and 20% of these patients achieved HBsAg loss, 6 months following discontinuation of peginterferon alfa-2a (40KD) (PEGASYS®, PegIFN alfa-2a) therapy.[3]
> – On-treatment HBV DNA levels may further improve prediction of sustained immune response.
> Response-guided therapy uses on-treatment response for early identification of patients less likely to respond to PegIFN alfa-2a therapy to allow timely individualisation of treatment. The remaining patients can be motivated to complete PegIFN alfa-2a therapy.
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>  Objective
> To identify how response to PegIFN alfa-2a can be optimised through treatment extension or combination with nucleos(t)ide analogues using a response-guided treatment strategy.
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> Conclusions
> Early responders achieved higher rates of HBeAg seroconversion at Weeks 48 and 72 than non-early responders.
> – HBsAg and HBV DNA declines from baseline to Week 72 were also more pronounced.
> – In early and non-early responders who have completed treatment, HBeAg seroconversion rates continued to increase 6 months post-treatment.
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> The findings of this interim analysis are consistent with the association between on-treatment reduction of HBsAg and HBV DNA levels and sustained immune response. Results from Arms C and D, expected in 2013, will provide information regarding outcomes in non-early responders with treatment modification. The study will provide valuable information on how response to PegIFN alfa-2a can be optimised in patients with HBeAg-positive CHB.
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StephenW

>简介
对于乙肝患者Ë抗原（HBeAg）阳性的慢性乙型肝炎（CHB），聚乙二醇干扰素治疗停药后HBeAg转阴或血清学转换相关的后续的机会增加乙肝表面抗原（HBsAg）的亏损，[1]和改进长期的临床结果。[2]
早期治疗的HBsAg下降相关治疗后持久的免疫控制。
>  - 在以前的回顾性分析，确定可能实现持续应答的患者对治疗乙肝表面抗原定量评估的价值，人们发现，54％的患者乙肝表面抗原<1500 IU / mL的周24实现HBeAg血清学转换和20 ％的患者达到HBsAg消失，6个月，停药后的聚乙二醇化干扰素α-2a（40KD）（派罗欣®，PegIFN干扰素α-2a）治疗。[3]
>  - 治疗HBV DNA水平可能进一步提高预测的持续的免疫反应。
>响应引导治疗使用的治疗反应，患者不太可能回应PegIFN干扰素α-2a治疗，以便及时治疗个体化的早期识别。其余患者可以积极完成PegIFN干扰素α-2a治疗。
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>目标
要确定如何响应PegIFN干扰素α-2a可以通过治疗延长或核苷（酸）类似物使用响应指导治疗策略结合优化。
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>结论
>早期反应实现周时HBeAg血清转换率较高的48和72比非早期应答。
>  -  HBsAg和HBV DNA下降，从基线到72周也更加明显。
>  - 已完成治疗的早期和非早期应答，HBeAg血清转换率持续增加治疗后6个月。
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>本中期分析结果是一致的，减少对治疗的HBsAg和HBV DNA水平和持续的免疫反应之间的关联。结果从武器C和D，预计在2013年，将提供有关非早期反应治疗修改的结果。这项研究将提供有价值的信息，如何响应PegIFN干扰素α-2a HBeAg阳性CHB患者，可以优化。
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StephenW

- This was a randomised, open-label study. Patients diagnosed with HBeAg-positive CHB who had not received any antiviral treatment for at least 6 months were enrolled (N=265) and received PegIFN alfa-2a 180μg/week for 24 weeks.
- Early responders were defined by Week 24 HBsAg <1500 IU/mL and HBV DNA <105 copies/mL.
- Early responders (Arm A) continued PegIFN alfa-2a for a further 24 weeks (total treatment duration48 weeks; n=66) (Figure 1).
- Non-early responders (patients who did not achieve the early response criteria) were randomised 1:1:1 to three study arms (Figure 1):
              Arm B: continued PegIFN alfa-2a for a further 24 weeks (total treatment duration 48 weeks; n=67)
              Arm C: continued PegIFN alfa-2a for a further 72 weeks (total treatment duration 96 weeks; n=67)
               Arm D: continued PegIFN alfa-2a for a further 72 weeks, plus adefovir add-on at Week 29 for 36 weeks (total treatment duration 96 weeks; n=64).
Patients were followed up for 24 weeks post-treatment. Currently for this interim analysis only patients in Arms A and B have completed follow-up.
The primary endpoint was change from baseline of quantitative HBsAg after 24 weeks of follow-up.
This interim analysis describes treatment response up to Week 72.
- 这是一项随机，开放标签研究。患者确诊HBeAg阳性CHB谁没有接受任何抗病毒治疗至少6个月的患者（n =265）和接收PegIFN干扰素α-2a180μg/week24周。
- 早者定义：第24周时HBsAg的<1500 IU/ mL和HBV DNA<105拷贝/ ml。
- 早期应答继续PegIFN干扰素α-2a（A组）为24周（总治疗duration48周，N= 66）（图1）。
- 非早期应答者（患者没有达到早期反应标准）被随机1:1:1三个研究组（图1）：
              B组：继续PegIFN干扰素α-2a，另有24周（总疗程48周，N= 67）
              ARM C：继续PegIFN干扰素α-2a为72周（总疗程96周，N= 67）
               ARM的D：继续PegIFN干扰素α-2a为72周，加上阿德福韦在第29周，36周（总疗程96周，N=64）。
术后随访24周治疗后。目前本中期分析患者武器A和B已完成跟进。
主要终点是从基线HBsAg定量变化，24周后的随访。
本中期分析介绍了72周的治疗反应。

StephenW

StephenW

咬牙硬挺

感谢分享，有无e抗原阴性hbv的派罗欣治疗数据？据说复发率很高？