接受恩替卡韋+ARC-520治療的中國慢性乙型肝炎患者

乙肝人1949

一个老同志的偏陕I心态。就是我不能用。我也不希望大家用。

StephenW

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AASLD名家访谈︱宁琴教授：基于PEG IFNα的多靶点联合治疗方案可进一步提高慢乙肝临床治愈率——Anchor研究96周结果
2019-11-14 19:06
https://www.sohu.com/a/353823405_120051436
编者按：近年来基于聚乙二醇干扰素α（PEG IFNα）的联合治疗策略提升慢乙肝临床治愈率的循证医学证据越来越多。随着慢乙肝指南的更新和临床治愈专家共识的发布，基于PEG IFNα的多靶点联合治疗慢乙肝的理念已逐渐被专家关注和认可。我国华中科技大学同济医学院附属同济医院宁琴教授团队的一项关于PEG IFNα-2b（派格宾®）联合治疗慢乙肝核苷经治患者的临床研究——Anchor研究继2017年应邀美肝会口头交流后，2019年再次应邀口头交流。2019年11月11日，第70届美国肝病研究学会（AASLD）年会期间，吴迪副教授做了精彩的口头报告，现场交流环节与会专家进行了热烈讨论。

以下是AASLD 2019 吴迪口头报告:

157
Combination of Na, Peg‐IFN Alpha‐2b and GMCSF Enhanced HBsAB Production in NA Suppressed CHB Patients (The Anchor a Study): An Interim Analysis

Di Wu 1, Weiming Yan1, Deming Tan2, Shifang Peng3, Yongping Chen4, Jiaji Jiang5, Xinyue Chen6, Xiaoguang Dou7, Ke Ma1, Peng Wang1, LI SUN8, Ping Yin9, Meifang Han1, Qin Ning1 (1) Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, (2) Xiangya Hospital, Central South University, Changsha, China, (3) Xiangya Hospital, Central South University, (4) The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, (5) First Affiliated Hospital of Fujian Medical University, (6) Youan Hospital, Capital Medical University, (7) Shengjing Hospital of China Medical University, (8) Xiamen Amoytop Biotech Co., Ltd, (9) Tongji Medical College, Huazhong University of Science and Technology

Background: Granulocyte‐macrophage colony stimulating factor (GMCSF) has various effects on immune responses and has previously been used as an adjuvant to HBV vaccine to increase the antibody response. This multicenter, randomized controlled trial (NCT02327416) was to evaluate whether combination of NA, peginterferon alfa‐2b (Peg‐IFN α‐2b) and GMCSF could induce HBsAg loss/seroconversion in patients undergoing long‐term NA. Methods: 249 CHB patients who had received NA>1 year, with HBsAg <3000 IU/ml and HBV DNA ⩽1000 copies/ml, were randomized 1:1:1 to receive ETV for 96 weeks (Group I) or ETV for 48 weeks and Peg‐IFN a‐2b (180 μg/week) for 96 weeks (Group II) or ETV and intermittent GMCSF (75 μg/day, first 5 days each month) for 48 weeks plus Peg‐IFNα‐2b for 96 weeks (Group III). Interim data on 249 patients (81 in Group I, 83 in Group II and 85 in Group III) were analyzed. Results: Baseline characteristics were comparable among treatment groups. At week 96, patients receiving NA+ Peg‐IFN+ GMCSF and patients receiving NA+ Peg‐IFN achieved higher rates of HBsAg loss than those continuing NA treatment (19.40%, 31.34% and 0%, respectively, p < 0.001 for all comparisons vs Group I). There was no significant difference in HBsAg loss rate between Group III and Group II (p =0.527). HBsAb appearance rates were significantly higher in Group III (34.43%) and Group II (32.76%) than Group I (0%, p < 0.001 for all comparisons vs Group I). HBsAg seroconversion was only observed in Group III (20.69%) and Group II (27.87%) (p =0.3619). At week 12 after initiating Peg‐IFN, 58 patients in Group III and 47 in Group II experienced ALT elevation (12×ULN), among these subgroup of patients, NA+ Peg‐IFN+ GMCSF induced significantly higher HBsAb appearance rates than NA+ Peg‐IFN (48.28% vs 29.79%) at week 96. The difference between the two groups and the 95% CI was 18.49% (0.15% to 36.83%), which was statistically significant. Moreover, numerically higher rates of HBsAb>100IU/L were observed in Group III than in Group II at week 96 (17.24% vs 8.51%, p=0.19). Both dual and triple combination therapy regimens were generally well‐tolerated. Conclusion: For patients who achieved virological suppression with NA, a combination of ETV and Peg‐IFN α‐2b therapy with or without GMCSF significantly increases rates of HBsAg loss/seroconversion. GMCSF when combined with Peg‐IFN α‐2b may enhance HBsAb appearance rates, particularly in those who experienced early on‐treatment ALT elevation.
157
Na，Peg-IFN Alpha-2b和GMCSF联合使用可在NA抑制的CHB患者中增强HBsAB的产生（锚定研究）：一项中期分析

吴迪1，严卫明1，谭德明2，彭世芳3，陈永平4，贾佳江5，陈新月6，窦光光7，柯马1，彭望1，李孙8，平阴9，韩美芳1，秦宁1（1）同济医学院附属同济医院华中科技大学学院，（2）中南大学湘雅医院，中国长沙，（3）中南大学湘雅医院，（4）温州医科大学附属第一医院，中国温州，（ 5）福建医科大学附属第一医院，（6）首都医科大学附属佑安医院，（7）中国医科大学附属盛京医院，（8）厦门厦门阿波托生物技术有限公司，（9）华中大学同济医学院科学技术学院

背景：粒细胞-巨噬细胞集落刺激因子（GMCSF）对免疫反应具有多种作用，以前曾被用作HBV疫苗的佐剂以增加抗体反应。这项多中心随机对照试验（NCT02327416）旨在评估NA，peginterferon alfa-2b（Peg-IFNα-2b）和GMCSF的组合是否可在接受长期NA的患者中诱发HBsAg丧失/血清转化。方法：将249例接受NA≥1年，HBsAg <3000 IU / ml和HBV DNA copies1000拷贝/ ml的CHB患者按1：1的比例随机分组接受ETV治疗96周（第一组）或ETV治疗48周每周96周（第II组）和Peg‐IFN a-2b（180μg/周）（第二组）或ETV和间歇性GMCSF（每月75μg/天，每月前5天）持续48周，以及Peg‐IFNα-2b（96周） （第三组）。分析了249例患者的中期数据（第一组81例，第二组83例，第三组85例）。结果：治疗组之间的基线特征具有可比性。在第96周，接受NA + Peg-IFN + GMCSF的患者和接受NA + Peg-IFN的患者的HBsAg丢失率高于继续接受NA治疗的患者（分别为19.40％，31.34％和0％，与组I相比，所有比较的p <0.001 ）。第三组和第二组之间的HBsAg丢失率无显着差异（p = 0.527）。第三组（34.43％）和第二组（32.76％）的HBsAb出现率显着高于第一组（0％，与第一组相比，所有比较的p <0.001）。 HBsAg血清转化仅在第三组（20.69％）和第二组（27.87％）中观察到（p = 0.3619）。在开始使用Peg-IFN后的第12周，III组中的58例患者和II组中的47例患者出现了ALT升高（12×ULN），在这些亚组患者中，NA + Peg-IFN + GMCSF诱导的HBsAb出现率明显高于NA + Peg-IFN。在第96周时（48.28％比29.79％）。两组和95％CI的差异为18.49％（0.15％至36.83％），具有统计学意义。此外，在第96周时，第三组的HBsAb> 100IU / L发生率高于第二组（17.24％对8.51％，p = 0.19）。双重和三次联合治疗方案通常耐受性良好。结论：对于通过NA进行病毒学抑制的患者，ETV和Peg‐IFNα-2b治疗联合或不联合GMCSF均可显着提高HBsAg丧失/血清转化率。 GMCSF与Peg‐IFNα-2b联合使用可能会提高HBsAb出现率，特别是在治疗早期出现ALT升高的患者中。

宁琴教授在美肝会发表干挠素研究，演讲，这些证据够不够？读者自己决定 !

乙肝人1949

有什么问题吗？伱要表达啥？Na＋干扰素大概有3o％以上的Hbsag丢失率。即表面抗原为0。效果很好啊一一

乙肝人1949

GMcsF，联合或不联合，差不多效果。无太大统计差异

乙肝人1949

开始找细节，挑刺，哈哈哈。套路来吧

StephenW

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自便 , 如果你接受风险和利益.

StephenW

https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.30940
193
Switch Or Add‐On Peginterferon To Chronic Hepatitis B Patients Already On Nucleos(T)Ide Analogue Therapy (Swap Study): Final Results

Seng Gee Lim 1, Wei Lyn Yang2, Jason Pik Eu Chang3, Jeffrey Ngu4, Yi ‐Lyn Jessica Tan5, Taufique Ahmed6, Yock Young Dan7, Yin Mei Lee8, Guan Huei Lee8, Poh Seng Tan9, Wah Wah Phyo10, Lay Wai Khin11, Chris Lee10, Amy Tay10, Edwin Chan12 (1) Gastroenterology & Hepatology, National University Health System, (2) Dept of Gastroenterology, Tan Tock Seng Hospital, (3) Duke‐Nus Medical School, Singapore, (4) Dept of Gastroenterology, Singapore General Hospital, (5) Dept of Gastroenterology, Changi General Hospital, (6) Jerudong Park Medical Centre, (7) Division of Gastroenterology & Hepatology, National University Health System, Singapore, (8) Division of Gastroenterology & Hepatology, National University Health System, (9) Division of Gastroenterology and Hepatology, National University Health System, Singapore, (10) Dept of Medicine, Yong Loo Lin School of Medicine, (11) Perinatal Audit and & Epidemiology Unit, Kandang Kerbau Hospital, (12) Duke‐Nus School of Medicine

Background: It is unclear whether add‐on or switch to peginterferon alpha (PEG) in patients on long term nucleos(t) ide analogue (NA) therapy is more efficacious for HBsAg loss, hence we conducted a randomised control trial(RCT) to address this. Methods: This was a multicentre RCT of add‐on[AO] or switch[S] to PEG(pegintron, Merck, USA) for 48 weeks, versus continuing NA randomised 2:2:1 (clinicaltrial. gov NCT01928511). Patients were enrolled from five public hospitals in Singapore, approved by IRB(DSRB2012/01039). Computer randomisation stratified patients by HBeAg status, high/low genetic barrier NA, or fibroscan score. Eligibility: HBsAg>6months, NA>12 months, compensated cirrhosis and undetectable HBVDNA. Exclusions: telbivudine, decompensated cirrhosis, significant co‐morbidities. The primary endpoint was a composite of qHBsAg>1log reduction or HBeAg loss, and secondary endpoint was HBsAg loss at week 72. A study size of 255 patients had a 80% power to detect a 30% difference between AO/S versus NA. Analysis was by intention‐to‐treat(ITT) using SPSSv20. Results: A total of 253 (AO 78, S 79, NA 42) patients were randomised. ITT analysis at week 72, found qHBsAg>1 log (IU/ml) reduction in 18/99(18%) in AO, 21/103 (20%) in S and 1/51(2%) in NA(p<0.05 vs NA). HBeAg loss occured in 5/29 (17%) in AO arm, 11/37 (30%) in S and 0% in NA(p=ns). The primary endpoint occured in 31/99 (31%) in AO, 35/103 (34%) in S and 1/51(2%) in NA (p<0.0001 vs NA). HBsAg loss was seen in 9/99 (10%)in AO, 8/103 (8%) in S and 0% a Denotes AASLD Foundation Abstract Award Recipient in NA (p=0.026 AO vs NA, p=0.041 S versus NA). Baseline qHBsAg[bqHBsAg]<48IU/ml was a predictor of HBsAg loss for AO while S had higher bqHBsAg <310 IU/ml as a predictor of HBsAg loss (p=0.026). HBV reactivation was seen in 16/53 (30.2%) in S 1/51 (2%) in AO and 1/30 (3.3%) NA(p<0.004 in S vs AO or NA). On multivariate analysis, bqHBsAg(logIU/ml),week 8 qHBsAg log difference from baseline, and age were independent predictors of HBsAg loss with AUROC=0.96 (0.93‐0.997),p<0.001. There were 38(15.0%) discontinuations/withdrawals during therapy(11 from adverse events[AE]) 1511AEs, 14serious adverse events. There was one death due to myocardial infarction. The most common AEs were interferon‐related. Conclusion: Final results of the SWAP study showed no significant difference between S and AO to NA, with bqHBsAg, week 8 qHBsAg difference and age being independent predictors. However, AO required a much lower bqHBsAg to achieve HBsAg loss compared to S.

193
已经对Nucleos（T）Ide类比疗法（交换研究）的慢性乙型肝炎患者切换或加用聚乙二醇干扰素治疗：最终结果

Seng Gee Lim 1，Wei Lyn Yang2，Jason Pik Eu Chang3，Jeffrey Ngu4，Yi ‐Lyn Jessica Tan5，Taufique Ahmed6，Yock Young Dan7，Yin Mei Lee8，Guan Huei Lee8，Poh Seng Tan9，Wah Wah Phyo10，Lay Wai Khin11，克里斯·李（Chris Lee）10，艾米·泰（Amy Tay）10，埃德温·陈（Edwin Chan）12（1）国立大学卫生系统胃肠病学和肝病学（2）陈笃生医院消化内科（3）新加坡杜克-努斯医学院（4）新加坡总医院，（5）樟宜综合医院消化内科，（6）Jerudong Park医学中心，（7）新加坡国立大学卫生系统消化内科和肝病科，（8）国立大学消化内科和肝病科卫生系统，（9）新加坡国立大学卫生系统胃肠病学和肝病科，（10）Yong Loo Lin医学院，医学系，（11）甘丹克尔堡医院围产期审计和流行病学科，（12）杜克努斯医学院

背景：尚不清楚长期接受核苷酸（t）类似物（NA）治疗的患者是否增加或改用聚乙二醇干扰素α（PEG）对HBsAg丢失更有效，因此我们进行了一项随机对照试验（RCT）解决这个问题。方法：这是一个多中心RCT，使用附加[AO]或切换[S]进行PEG（pegintron，默克公司，美国）进行了48周，而连续的NA随机化为2：2：1（clinicaltrial.gov NCT01928511）。经IRB（DSRB2012 / 01039）批准，患者来自新加坡的五家公立医院。计算机随机分组通过HBeAg状态，高/低遗传屏障NA或纤维扫描评分对患者进行分层。资格：HBsAg> 6个月，NA> 12个月，肝硬化和无法检测到的HBVDNA。排除：替比夫定，失代偿性肝硬化，重大合并症。主要终点是qHBsAg> 1log降低或HBeAg减少的复合，次要终点是HBsAg减少在第72周。研究规模为255名患者，有80％的能力可以检测AO / S与NA之间的30％差异。使用SPSSv20通过意向性治疗（ITT）进行分析。结果：总共253例患者（AO 78，S 79，NA 42）被随机分组​​。 ITT分析在第72周发现AO中18/99（18％），S中21/103（20％）和NA（1/51（2％））中的qHBsAg> 1 log（IU / ml）降低（p < 0.05 vs.NA）。 HBeAg丢失发生在AO组的5/29（17％），S组的11/37（30％）和NA的0％（p = ns）。主要终点发生在AO的31/99（31％），S的35/103（34％）和NA的1/51（2％）（p <0.0001 vs NA）。 HBsAg丢失在AO中占9/99（10％），在S中占8/103（8％），0％a表示NA中AASLD基金会摘要奖的获得者（p = 0.026 AO vs NA，p = 0.041 S vs NA ）。基线qHBsAg [bqHBsAg] <48IU / ml是AO HBsAg丢失的预测指标，而S的bqHBsAg <310 IU / ml则是HBsAg丢失的预测指标（p = 0.026）。在AO的S 1/51（2％）中有16/53（30.2％）的HBV和在NA的1/30（3.3％）中有HBV的再激活（S vs AO或NA中p <0.004）。在多变量分析中，bqHBsAg（logIU / ml），第8周与基线的qHBsAg对数差异和年龄是HBsAg丢失的独立预测因素，AUROC = 0.96（0.93-0.997），p <0.001。治疗期间停药/停药38例（15.0％）（不良事件[AE] 11例）1511 AEs，14例严重不良事件。因心肌梗塞死亡1例。最常见的不良事件与干扰素有关。结论：SWAP研究的最终结果显示S和AO与NA之间无显着差异，bqHBsAg，第8周qHBsAg差异和年龄是独立的预测因子。但是，与S相比，AO需要更低的bqHBsAg来实现HBsAg的损失。

newchinabok

StephenW 发表于 2021-4-9 14:20
回复 乙肝人1949 的帖子

自便 , 如果你接受风险和利益.

国际巨头三联疗法核苷+核衣壳+干挠素

乙肝人1949

哈哈哈哈哈，天上一脚，地上一脚，看似聪明。

newchinabok

你说老外停止研究，我不认为这仍然是正确的