AASLD2014:预测聚乙二醇干扰素α治疗HBeAg阳性响应概率

StephenW

1904Estimating The Probability Of Response To Peginterferon Alfa In Hbeag-Positive Chronic Hepatitis B: The Epic-B Predictor


Milan J. Sonneveld1, Vincent W. Wong2, Jun Cheng3, Teerha Piratvisuth4, Jidong Jia5, Stefan Zeuzem6, Edward J. Gane7, Yun -Fan Liaw8, Willem Pieter Brouwer1, Qing Xie9, Jinlin Hou10, Henry Lik-Yuen Chan2, Harry L. Janssen1,11, Bettina E. Hansen1;1Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands; 2Department of Medicine and Therapeutics and Institute of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China; 3Beijing Ditan Hospital, Beijing, China; 4NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Hat Yai, Thailand; 5Liver Research Center, Beijing Friendship Hospital, Beijing, China; 6Medical Clinic 1, Johann Wolfgang Goethe University Medical Center,, Frankfurt, Germany; 7Liver Unit, Auckland City Hospital, Auckland, New Zealand; 8Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan; 9Department of Infectious Diseases, Ruijin Hospital, Shanghai, Chile; 10Department of Infectious Diseases, Nanfang Hospital, Guangzhou, China; 11Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada
Background. Only a subset of chronic hepatitis B patients achieves a response to peginterferon (PEG-IFN) therapy.

Methods. A baseline prediction model (EPIC-B Predictor) for response (HBeAg loss and HBV DNA <2,000IU/mL at 6 months post-treatment) was constructed based on HBV genotype, baseline HBsAg, HBV DNA, ALT and patient age, sex and previous IFN therapy in a training dataset of 822 HBeAg-positive patients treated with PEG-IFN for one year in 3 global randomized trials (Pegasys Phase 3, HBV 99-01 and Neptune) and externally validated in 666 patients treated with PEG-IFN for 24 to 48 weeks in various global studies. Patients were classified according to the predicted probability of response: low (<20%), intermediate (20-30%) or high (>30%). Response was defined as HBeAg loss with HBV DNA <2,000 IU/mL at 6 months post-treatment.

Results. The derivation dataset consisted of genotypes A/B/C/D in 112/206/392/112. Genotype specific models were constructed for genotypes A, B and C, but not D because of the limited number of responders. The model performed well in the training set (AUROC 0.71, p<0.001) and predicted probabilities from the model accurately reflected observed response rates (table). In the validation cohort (genotypes A/B/C in 9/272/385, full year of treatment 33%, response 17%), the model performed well (AUROC 0.67, p<0.01) and the predicted probability strongly correlated with observed response rates (p<0.001). The EPIC-B predictor consistently identified subsets of patients with low (∼40% of patients in both datasets) or high chances of response (∼30% of patients in both datasets).

Conclusions. The EPIC-B Predictor accurately estimates the probability of response to PEG-IFN therapy in HBeAg-positive patients and can be used to improve patient counselling and to guide the choice of first-line treatment in HBeAg-positive chronic hepatitis B.
Observed response rates by predicted probability

Only a subset of patients in the validation dataset received PEG-IFN for one year. Higher EPIC-B predicted probability was associated with higher response rates regardless of therapy duration.
Disclosures:
Milan J. Sonneveld - Advisory Committees or Review Panels: Roche; Speaking and Teaching: Roche, BMS
Vincent W. Wong - Advisory Committees or Review Panels: Abbvie, Gilead; Consulting: Merck, NovaMedica; Speaking and Teaching: Gilead, Echosens
Teerha Piratvisuth - Advisory Committees or Review Panels: Merck; Grant/ Research Support: Roche, Novartis, Bristol Myers Aquibb, Roche, Bristol Myers Squibb, Fibrogen; Speaking and Teaching: Merck, Roche, Novartis, GlaxoSmith-Kline, Bristol Myers Squibb
Jidong Jia - Consulting: BMS, GSK, MSD, Novartis, Roche
Stefan Zeuzem - Consulting: Abbvie, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Co., Gilead, Novartis Pharmaceuticals, Merck & Co., Idenix, Janssen, Roche Pharma AG, Vertex Pharmaceuticals
Edward J. Gane - Advisory Committees or Review Panels: Novira, AbbVie, Novartis, Gilead Sciences, Janssen Cilag, Vertex, Achillion, Tekmira, Merck, Ide-nix; Speaking and Teaching: AbbVie, Novartis, Gilead Sciences, Janssen Cilag
Yun -Fan Liaw - Advisory Committees or Review Panels: Roche; Grant/Research Support: Roche
Jinlin Hou - Consulting: Roche, Novartis, GSK, BMS; Grant/Research Support:
Roche, Novartis, GSK
Henry Lik-Yuen Chan - Advisory Committees or Review Panels: Gilead, MSD, Bristol-Myers Squibb, Roche, Novartis Pharmaceutical; Speaking and Teaching: Echosens, Abbvie
Harry L. Janssen - Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris
The following people have nothing to disclose: Jun Cheng, Willem Pieter Brou-wer, Qing Xie, Bettina E. Hansen

StephenW

1904
估计响应概率聚乙二醇干扰素α治疗HBeAg阳性慢性乙型肝炎：史诗-B预测
米兰J. Sonneveld1，文森特·W·Wong2，君Cheng3，Teerha Piratvisuth4，冀东Jia5，斯特凡Zeuzem6，爱德华·J·Gane7，云 - 风扇Liaw8，威廉·彼得Brouwer1，清Xie9，吉林Hou10，亨利沥元CHAN2，哈里L 。Janssen1,11，贝蒂娜E. Hansen1;
1Gastroenterology和肝病，伊拉兹马斯MC大学医学中心鹿特丹，鹿特丹，荷兰;教研室内科及药物治疗，消化道疾病，香港，中国香港的中国大学研究所; 3Beijing地坛医院，北京，中国;胃肠病学和肝病，Songklanagarind医院，合艾，泰国4NKC研究所; 5Liver研究中心，北京友谊医院，北京，中国; 6Medical诊所1，约翰·沃尔夫冈·歌德大学医学中心,,德国法兰克福; 7Liver单位，奥克兰市医院，奥克兰，新西兰; 8Liver研究单位，长庚医院，台北，台湾;传染病9Department，瑞金医院，上海，智利;传染病10Department，南方医院，广州，中国; 11Toronto中心肝病大学健康网络，多伦多，加拿大

背景。慢性乙肝患者的一个子集，以达到聚乙二醇干扰素（PEG-IFN）治疗的反应。方法。基线预测模型（EPIC-B预测）的响应（HBeAg阴转率和HBV DNA<2,000IU/毫升，6个月后的治疗）的基础上HBV基因型构成，基准线的HBsAg，HBV DNA，ALT和患者的年龄，性别，以前的干扰素治疗与PEG-IFN在3全球随机试验治疗一年822例HBeAg阳性患者训练数据集（派罗欣三期，HBV99-01和海王星）和外部验证666例PEG-IFN治疗24至48周的各种全球性研究。低（<20％），中间（20-30％）或高（> 30％）：患者根据响应的预测概率进行分类。反应定义为HBeAg消失与HBV DNA<2000 IU/ mL的6个月后处理。结果。在112/206/392/112推导数据集组成的基因型A / B/ C/ D。基因型的具体型号分别构建了基因型A，B和C，但不是D，因为响应者的数量有限。在训练集中表现良好的模型（AUROC0.71，P <0.001），并预测从概率模型准确地反映观察到的应答率（表）。在验证队列（基因型A / B/ C的9/272/385，治疗33％全年，应对17％），该模型表现良好（AUROC0.67，P <0.01），预测概率与观测到的强相关应答率（P <0.001）。在EPIC-B的预测一致认定患者亚群或响应的机率较高（患者在这两个数据集的约30％），低（在这两个数据集的病人〜40％）。结论。 EPIC的-B的预测准确估计响应的PEG-IFN治疗的HBeAg阳性患者的概率，并且可以用于改善患者咨询和引导一线治疗方案的选择中HBeAg阳性慢性乙型肝炎

观察到的响应率按预测概率
图片

患者在验证数据集的一个子集接受PEG-IFN一年。高EPIC-B的预测概率较高反应率相关，无论治疗时间。

披露：

米兰J. Sonneveld - 咨询委员会或审查小组：罗氏公司;说起与教学：罗氏，拜耳

文森特·W·皇 - 咨询委员会或审查小组：Abbvie，基列;咨询：默克，NovaMedica;说起与教学：Gilead公司，Echosens

Teerha Piratvisuth - 咨询委员会或审查小组：默克公司;格兰特/研究支持：罗氏，诺华，百迈尔斯Aquibb，罗氏，百美施贵宝，纤维蛋白原;说起与教学：默克，罗氏，诺华，GlaxoSmith，克莱恩，布里斯托尔Myers Squibb公司

冀东佳 - 咨询：BMS，GSK，MSD，诺华，罗氏

斯特凡Zeuzem - 咨询：Abbvie，勃林格殷格翰，百时美施贵宝公司，Gilead公司，诺华制药公司，默克公司，Idenix公司，西安杨森，罗氏制药公司，Vertex制药公司

爱德华·J·甘恩 - 咨询委员会或审查小组：Novira，AbbVie，诺华公司，Gilead Sciences公司，西安杨森Cilag公司，顶点，艾琪尔顿，Tekmira，默克，IDE-nix的;说起与教学：AbbVie，诺华，Gilead Sciences公司，西安杨森Cilag公司

韵 - 风扇LIAW - 咨询委员会或审查小组：罗氏公司;格兰特/研究支持：罗氏

吉林侯 - 咨询：罗氏，诺华，葛兰素史克，BMS;格兰特/研究支持：

罗氏，诺华，葛兰素史克

亨利沥，陈婉 - 咨询委员会或审查小组：Gilead公司，MSD，施贵宝，罗氏，诺华制药;说起与教学：Echosens，Abbvie

哈里L.詹森 - 咨询：雅培，百美施贵宝，DEBIO，Gilead Sciences公司，默克公司，美敦力，诺华，罗氏，Santaris;格兰特/研究支持：Anadys，布里斯托尔Myers Squibb公司，Gilead Sciences公司，Innogenetics公司，麒麟，默克公司，美敦力，诺华，罗氏，Santaris

下面的人都没有透露：郡城，威廉·彼得·布鲁-WER，清泄，贝蒂娜汉森

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