AASLD2014:HBsAg清除另外48周PEGIFN的HBeAg阴性慢性乙型肝炎患者对

StephenW

1863HBsAg clearance after addition of 48 weeks of PEGIFN in HBeAg negative CHB patients on Nucleos(t)ide therapy with undetectable HBV DNA for at least one year: a multicenter randomized controlled phase III trial ANRS-HB06 PEGAN study: preliminary findings
Marc Bourliere1, Pascaline Rabiega2, Nathalie Ganne-Carrie4, Lawrence Serfaty5, Patrick Marcellin6, Noelle Pouget2, Dominique Guyader7, Christophe Hezode8, Magali Picon9, Xavier Causse10, Vincent Leroy11, Jean-Pierre Bronowicki12, Ghassan Riachi13, Isabelle Rosa14, Pierre Attali15, Jean-Michel Molina16, Yannick Bacq17, Albert Tran18, Jean Didier Grange19, Fabien Zoulim20, Helene Fontaine21, Inga Bertucci22, Magali Bouvier-Alias23, Fabrice Carrat2, Yves Benhamou3;1hepato-gastroenterology, hopital saint joseph, Marseille, France; 2INSERM UMR-S1136, Medical school Saint Antoine, Paris, France; 3Hepato-Gastroenterology, Pitie Salpetriere University Hospital, Paris, France; 4Hepato-Gastroenterology, Jean Verdier Hospital, Bondy, France; 5Hepato-Gastroenterology, Saint Antoine hospital, Paris, France; 6Hepatology, Beaujon Hospital, Clichy, France; 7Hepatology, Pontchaillou University Hospital, Rennes, France; 8Hepato-Gastroenterology, Henri Mondor University Hospital, Creteil, France; 9Hepato-Gastroenterology, Aix General Hospital, Aix en provence, France; 10Hepato-Gastroenterology, La source Hospital, Orleans, France; 11Hepato-Gastroenterology, University Hospital, Grenoble, France; 12Hepato-Gastroenterology, Brabois University Hospital, Nancy, France; 13Hepato-Gastroenterology, Charles Nicolle Hospital, Rouen, France; 14Hepato-Gastroenterology, Intercommunal Hospital, Creteil, France; 15Hepato-Gastroenterology, Bicêtre Hospital, Le Kremlin Bicêtre, France; 16Infectious diseases, Saint Louis Hospital, Paris, France; 17Hepato-Gastroenterology, Trousseau Hospital, Tours, France; 18Hepato-Gastroenterology, Archet Hospital, Nice, France; 19Hepato-Gastroenterology, Tenon Hospital, Paris, France; 20Hepato-Gastroenterology, Hotel Dieu Hospital, Lyon, France; 21Hepato-Gastroenterology, Cochin Hospital, Paris, France; 22Viral hepatitis, INSERM-ANRS, Paris, France; 23Bacteriology and Immunology, INSERM U 635, Creteil, France
Background and Aims: Uncontrolled studies suggest that addition of PEGIFN in CHB patients receiving NUCs with unde-tectable serum HBV DNA may increase HBsAg clearance. We conducted a multicenter randomized controlled study to evaluate this strategy. Patients and methods: The key inclusion criteria were: HBeAg negative CHB and documented negative HBV DNA while on stable NUC regimens for at least 1 year. Patients with PEGIFN contra-indications were excluded. From Jan 2011 to July 2012, 183 patients (86 %male, mean age 47.6 years range 28-74, HBV DNA undetectable for 192 weeks range 17-685) were randomized to receive a 48 weeks course of 180 μg/w PEGIFN-alfa-2a (Pegasys) in addition to the backbone NUC regimens (Group 1: n=90) or no additional therapy (Group 2: n=93). Patients were stratified according to the HBsAg titers (< or ≥ 2.25 log IU/ml). NUC regimens remained unchanged during the study period up to week 144. Treatments discontinuation was allowed if HBsAg clearance was sustained for 24 weeks. Patients were seen monthly during the first 48 weeks, then every 3 months. The primary end point was the proportion of patients with serum HBsAg clearance at week 96. Secondary endpoints included HBsAg clearance at Week 48.
Preliminary Results: 85 patients initiated PEGIFN in group 1, 17 patients discontinued prematurely PEGIFN due to adverse events, and 4 patients had a dose reduction to 135μg/w. There was no discontinuation of the NUC regimens in all the patients of both groups. At week 48, 6 patients had an HBsAg clearance in group 1 and 1 in group 2 (p= 0.061). Demographic and baseline characteristics, CHB history and history of anti-HBV therapies were studied. HBsAg clearance at the end of PEGIFN treatment (W48) was associated with (1) baseline HBsAg titer (p= 0.018) and (2) history of HBeAg seroconversion prior to randomization (4/17 (23.5%) vs 2/61(3.3%))(p=0.0185).
Conclusion: Addition of a 48 weeks course of PEGIFN alfa-2a to oral anti-HBV therapy in HBeAg negative CHB patients with undetectable serum HBV DNA for at least 1 year: (1) Results in a low rate of HBsAg clearance (6/90 (6.6%)) and (2) Suggests that low baseline HBs Ag titers and a history of HBeAg seroconversion either spontaneously or under HBV therapy may increase HBsAg clearance rate.
Disclosures:
Marc Bourliere - Advisory Committees or Review Panels: Schering-Plough, Bohringer inghelmein, Schering-Plough, Bohringer inghelmein; Board Membership: Bristol-Myers Squibb, Gilead, Idenix; Consulting: Roche, Novartis, Tibotec, Abott, glaxo smith kline, Merck, Bristol-Myers Squibb, Novartis, Tibotec, Abott, glaxo smith kline; Speaking and Teaching: Gilead, Roche, Merck, Bristol-Myers Squibb
Nathalie Ganne-Carrie - Advisory Committees or Review Panels: Roche, Bayer; Speaking and Teaching: BMS, Gilead
Lawrence Serfaty - Board Membership: BMS, Gilead; Consulting: Merck; Speaking and Teaching: Roche, Janssen, Merck, Janssen, BMS, Gilead
Patrick Marcellin - Consulting: Roche, Gilead, BMS, Vertex, Novartis, Janssen, MSD, Abbvie, Alios BioPharma, Idenix, Akron; Grant/Research Support: Roche, Gilead, BMS, Novartis, Janssen, MSD, Alios BioPharma; Speaking and Teaching: Roche, Gilead, BMS, Vertex, Novartis, Janssen, MSD, Boehringer, Pfizer, Abbvie
Dominique Guyader - Advisory Committees or Review Panels: ROCHE, GILEAD,
IRIS, ABBVIE; Board Membership: MERCK; Grant/Research Support: JANSSEN;
Speaking and Teaching: BMS
Christophe Hezode - Speaking and Teaching: Roche, BMS, MSD, Janssen, abbvie, Gilead
Xavier Causse - Board Membership: Gilead, Janssen-Cilag; Grant/Research Support: Roche; Speaking and Teaching: Gilead, BMS, Janssen-Cilag
Vincent Leroy - Board Membership: roche, merck, gilead, bms, roche, merck, gilead, bms, roche, merck, gilead, bms, roche, merck, gilead, bms; Consulting: jansen, jansen, jansen, jansen; Grant/Research Support: roche, gilead, bms, roche, gilead, bms, roche, gilead, bms, roche, gilead, bms; Speaking and Teaching: bms, merck, gilead, roche, bms, merck, gilead, roche, bms, merck, gilead, roche, bms, merck, gilead, roche
Jean-Pierre Bronowicki - Consulting: Merck, Janssen, Boehringer Ingelheim, Gilead, BMS, Bayer, Novartis, GSK, Merck, Janssen, Boehringer Ingelheim, Gilead, BMS, Bayer, Novartis, GSK, ABBVIE; Speaking and Teaching: Roche, Merck, Janssen, BMS, Bayer, Roche, Merck, Janssen, BMS, Bayer
Pierre Attali - Consulting: cerba european lab; Management Position: Bioalliance Pharma; Stock Shareholder: Bioalliance Pharma, Sanofi
Jean-Michel Molina - Board Membership: Gilead, BMS, Janssen, merck, Abbott, boehringer; Grant/Research Support: merck; Speaking and Teaching: merck, gilead, BMS
Yannick Bacq - Speaking and Teaching: roche, gilead sciences, bristol-Myers Squibb
Albert Tran - Board Membership: BMS, Gilead
Fabien Zoulim - Consulting: BMS, Gilead, Roche; Grant/Research Support: BMS, Gilead, Roche; Speaking and Teaching: BMS, Gilead
Helene Fontaine - Independent Contractor: gilead, BMS, MSD, Roche, Janssen
Fabrice Carrat - Advisory Committees or Review Panels: BMS; Grant/Research Support: Janssen, Gilead, BMS, MSD, Abbvi
The following people have nothing to disclose: Pascaline Rabiega, Noelle Pouget, Magali Picon, Ghassan Riachi, Isabelle Rosa, Jean Didier Grange, Inga Bertucci, Magali Bouvier-Alias, Yves Benhamou

StephenW

1863
HBsAg清除另外48周PEGIFN的HBeAg阴性慢性乙型肝炎患者对核苷（酸）IDE治疗与检测不到HBV DNA，至少一年后的多中心随机对照III期试验ANRS-HB06佩甘的研究：初步调查结果
马克Bourliere1，帕斯卡利娜Rabiega2，娜塔莉Ganne-Carrie4，劳伦斯Serfaty5，帕特里克Marcellin6，诺伊尔Pouget2，多米尼克Guyader7，克里斯托夫Hezode8，马加利Picon9，泽维尔Causse10，文森特Leroy11，让 - 皮埃尔·Bronowicki12，加桑Riachi13，伊莎贝尔Rosa14，皮埃尔Attali15，让-Michel Molina16，亚尼克Bacq17，阿尔伯特Tran18，让迪迪埃Grange19，法比安斯基Zoulim20，海伦Fontaine21，因加Bertucci22，马加利布维尔-Alias23，法布里斯Carrat2，伊夫Benhamou3;
1hepato，消化内科，HOPITAL圣约瑟夫，马赛，法国; 2INSERM UMR-S1136，医学院圣安东尼，法国巴黎; 3Hepato，消化内科，Pitie妇女救济院大学医院，法国巴黎; 4Hepato，消化科，让迭尔医院，邦迪，法国; 5Hepato，消化内科，圣安东尼医院，法国巴黎; 6Hepatology，Beaujon医院，克利希，法国; 7Hepatology，Pontchaillou大学医院，法国雷恩; 8Hepato，消化内科，亨利·孟得尔大学医院，克雷泰伊，法国; 9Hepato，消化内科，艾克斯总医院，普罗旺斯地区艾克斯，法国; 10Hepato，消化内科，香格里拉源医院，新奥尔良，法国; 11Hepato，消化内科，大学医院，法国格勒诺布尔; 12Hepato，消化内科，Brabois大学医院，法国南锡; 13Hepato，消化内科，查尔斯·尼科尔医院，鲁昂，法国; 14Hepato，消化内科，社区间医院，克雷泰伊，法国; 15Hepato，消化内科，比塞特医院，乐克里姆林宫比塞特，法国; 16Infectious疾病，圣路易斯医院，法国巴黎; 17Hepato，消化内科，特鲁索医院，旅游，法国; 18Hepato，消化内科，阿切特医院，尼斯，法国; 19Hepato，消化内科，榫医院，法国巴黎; 20Hepato，消化内科，酒店Dieu酒店医院，法国里昂; 21Hepato，消化内科，交趾医院，法国巴黎; 22Viral肝炎，INSERM-ANRS，法国巴黎; 23Bacteriology与免疫学，INSERMü635，克雷泰伊，法国

背景和目的：不受控制的研究表明，除了PEGIFN在接受NUCs与UNDE-tectable血清HBV DNA慢性乙型肝炎患者可能会增加HBsAg清除。我们进行了一项多中心随机对照研究，以评估这一战略。患者和方法：关键的入选标准是：HBeAg阴性慢性乙型肝炎和记录负的HBV DNA，同时对稳定国统会方案治疗至少1年。患者PEGIFN禁忌症被排除在外。从2011年1月至2012年7月，183名患者（86％为男性，平均年龄47.6年范围28-74，HBV DNA检测不到的192周范围17-685）被随机分配接受48周当然是180微克/ W PEGIFN-ALFA -2a（派罗欣）除了主干NUC方案（第1组：N =90），或没有额外的治疗（第2组：N =93）。患者根据乙肝表面抗原滴度（<或≥2.25日志IU/ ml）的分层。国统疗法长达144周停药治疗研究期间也未发生变化，如果允许的HBsAg清除率持续24周。在第一个48周，然后每3个月的患者被认为每月。主要终点是患者的血清HBsAg清除率在本周96次要终点的比例包括乙肝表面抗原清除率在48周的初步结果：85例患者中1组发起PEGIFN，17名患者停药过早PEGIFN因不良事件，4例有一个剂量减少至135μg/瓦。有两个组的所有患者无中断的国统会的方案。在第48周，6例有乙肝表面抗原清除率在第1组和1组2（P =0.061）。人口统计学和基线特征，CHB历史和抗HBV治疗的历史进行了研究。 HBsAg清除在PEGIFN治疗结束（W48）与（1）乙肝表面抗原基线随机分组前（4月17日（23.5％）与2/61滴度的HBeAg血清学转换（P = 0.018）和（2）历史（3.3关联％））（P=0.0185）。结论：增加了一个48周当然PEGIFNα-2a的口服抗乙肝病毒治疗的HBeAg阴性慢性乙型肝炎患者检测不到血清HBV DNA至少1年：（1）结果HBsAg清除率较低（6/90 （6.6％））和（2）表明，低基线HBs抗体滴度银和HBeAg血清学转换的历史自发地或在乙肝治疗可能会增加HBsAg清除率。

披露：

马克Bourliere - 咨询委员会或审查小组：先灵葆雅，博赫林格inghelmein，先灵葆雅，博赫林格inghelmein;董事会成员：百时美施贵宝，吉利德，Idenix公司;咨询：罗氏，诺华，Tibotec公司，艾博特，葛兰素史克，默克，施贵宝，诺华，Tibotec公司，艾博特，葛兰素史克;口语和教学：Gilead公司，罗氏，默克，施贵宝

娜塔莉Ganne - 凯莉 - 咨询委员会或审查小组：罗氏，拜耳;口语和教学：BMS，吉利德

劳伦斯塞尔法蒂 - 董事会成员：BMS，基列;咨询：默克公司;口语和教学：罗氏，杨森，默克，杨森，拜耳，吉利德

帕特里克Marcellin - 咨询：罗氏公司，Gilead公司，拜耳，顶点，诺华，西安杨森，默沙东，Abbvie，Alios生物制药，Idenix公司，阿克伦城;格兰特/研究支持：罗氏公司，Gilead公司，拜耳，诺华，西安杨森，默沙东，Alios生物制药;口语和教学：罗氏，基列，拜耳，顶点，诺华，西安杨森，默沙东，勃林格，辉瑞，Abbvie

多米尼克Guyader - 咨询委员会或审查小组：罗氏，基列

虹膜，ABBVIE;董事会成员：默克;格兰特/研究支援：JANSSEN;

口语和教学：BMS

克里斯托夫Hezode - 口语与教学：罗氏，拜耳，默沙东，西安杨森，abbvie，吉利德

泽维尔喀斯 - 董事会成员：Gilead公司，扬森 -  Cilag公司;格兰特/研究支持：罗氏公司;口语和教学：Gilead公司，拜耳，杨森 -  Cilag公司

文森特乐华 - 董事会成员：罗氏，默克，吉利德，拜耳，罗氏，默克，吉利德，拜耳，罗氏，默克，吉利德，拜耳，罗氏，默克，吉利德，BMS;咨询：扬森，扬森，扬森，扬森;格兰特/研究支持：罗氏公司，Gilead公司，拜耳，罗氏，Gilead公司，拜耳，罗氏，Gilead公司，拜耳，罗氏，吉利德，BMS;口语和教学：BMS，默克，吉利德，罗氏，拜耳，默克，吉利德，罗氏，拜耳，默克，吉利德，罗氏，拜耳，默克，吉利德，罗氏

让 - 皮埃尔·Bronowicki - 咨询：默克，杨森，勃林格殷格翰，基列，拜耳，拜耳，诺华，葛兰素史克，默克，杨森，勃林格殷格翰，基列，拜耳，拜耳，诺华，葛兰素史克，ABBVIE;口语和教学：罗氏，默克，杨森，拜耳，拜耳，罗氏，默克，杨森，拜耳，拜耳

皮埃尔·阿塔利 - 咨询：cerba欧洲实验室;管理您的位置：Bioalliance医药;股股东：Bioalliance制药，赛诺菲安

让 - 米歇尔·莫利纳 - 董事会成员：Gilead公司，拜耳，西安杨森，默沙东，雅培，勃林格;格兰特/研究支援：默克公司;口语和教学：默克，吉利德，BMS

亚尼克Bacq - 口语与教学：罗氏公司，Gilead Sciences公司，百时美施贵宝

阿尔伯特陈德良 - 董事会成员：BMS，吉利德

法比安Zoulim - 咨询：BMS，Gilead公司，罗氏公司;格兰特/研究支持：BMS，Gilead公司，罗氏公司;口语和教学：BMS，吉利德

海琳方丹 - 独立承包商：Gilead公司，拜耳，默沙东，罗氏制药，西安杨森

法布里斯Carrat - 咨询委员会或审查小组：BMS;格兰特/研究支持：扬森，基列，拜耳，默沙东，Abbvi

下面的人都没有透露：帕斯卡利娜Rabiega，诺伊尔POUGET，马加利皮孔，加桑Riachi，伊莎贝尔·罗莎，让迪迪埃田庄，因加贝图西，马加利布维尔锯齿，伊夫本哈默

咬牙硬挺

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