AASLD2014:恩替 v 拉米 240周的治疗韩国的患者HBeAg阴性

StephenW

1909

A Comparison of the Efficacy and Safety of Entecavir Versus Lamivudine Through 240 Weeks of Treatment in Korean Patients with HBeAg-negative Chronic Hepatitis B

Kwan Sik Lee1, Young-Oh Kweon2, Soon Ho Um3, Byung-Ho Kim4, Young Suk Lim5, Seung Woon Paik6, Jeong Heo7, Heon Ju Lee8, Dong Joon Kim9, Tae Hun Kim10, Young Sok Lee11, Kwan Soo Byun12, Dae-Ghon Kim13, Myung Seok Lee14, Cyril Llamoso15, Kyungha Yu16, Dong Jin Suh17;

1Gangnam Severance Hospital, Yonsei University, Seoul, Republic of Korea; 2Kyungpook National University, Daegu, Republic of Korea; 3Korea University Anam Hospital, Seoul, Republic of Korea; 4Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea; 5Asan Medical Center, University of Ulsan, Seoul, Republic of Korea; 6Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea; 7Pusan National University Hospital, Busan, Republic of Korea; 8Yeungnam University Medical Center, Yeungnam University Hospital, Daegu, Republic of Korea; 9Chuncheon Sacred Heart Hospital, Hallym University, Chuncheon, Republic of Korea; 10Ewha Womans University Mokdong Hospital, Yangchoengu, Seoul, Republic of Korea; 11Bucheon St. Mary's Hospital, The Catholic University of Korea, Bucheon, Republic of Korea; 12Korea University Guro Hospital, Seoul, Republic of Korea; 13Chonbuk National University Hospital, Cheonju, Republic of Korea; 14Kang nam Sacred Heart Hospital, Hallym University, Seoul, Republic of Korea; 15Bristol-Myers Squibb, Wallingford, CT; 16Bristol-Myers Squibb, Seoul, Republic of Korea; 17Vievis Namuh Hospital, Seoul, Republic of Korea

Purpose: Long-term data on antiviral therapy in patients with HBeAg-negative chronic hepatitis B (CHB) are limited. We present the efficacy and safety of entecavir (ETV) compared with lamivudine (LAM) in treatment-naïve Korean patients with HBeAg-negative CHB over 240 weeks. Methods: Patients were randomized to receive either ETV 0.5 mg/day or LAM 100 mg/day during the initial double-blind phase of 96 weeks, followed by open-label treatment through to Week 240. The primary objective was the proportion of patients with virologic response (VR, <300 copies/mL by PCR) at Week 24. Secondary objectives included ALT normalization (ALT ≤1 × ULN) and emergence of ETV resistance at Week 96, and proportion of patients with VR and mean reduction from baseline HBV DNA levels at Week 240. Safety data reported throughout the study included adverse events (AEs), serious AEs (SAEs), laboratory abnormalities and discontinuation due to AEs.

Results: A total of 120 male and female patients (>16 years) were enrolled from 14 centers across Korea (ETV, n=56; LAM, n=64). There were no differences in baseline characteristics between the groups (Table). At Week 24, the proportion of patients with VR was significantly higher in the ETV group than in the LAM group (92.9% vs. 67.2%, p=0.0006), Week 96 (94.6% vs. 48.4%, p<0.0001) and Week 240 (95.0% vs. 47.6%, p<0.0001). At Week 96, ALT normalization was observed in 87.5% of ETV-treated and in 51.6% LAM-treated patients ( p<0.0001), while virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM ( p<0.0001). Emergence of resistance to ETV was not detected. Mean reduction in HBV DNA from baseline to Week 240 was −3.61 ±0.76 and −2.45 ±1.54 log10 copies/mL with ETV and LAM, respectively (p<0.0001). Overall, 11 SAEs were reported in 7 ETV-treated patients while 20 SAEs were reported in 17 LAM-treated patients ( p=0.055); however, these events were not related to either of the study medications.

Conclusions: Long-term therapy with ETV offers advantages over LAM, with significantly higher proportions of HBeAg-negative CHB patients achieving virologic response and ALT normalization. Both treatments were well tolerated.


Table. Baseline data and VR
Disclosures:
Young Suk Lim - Grant/Research Support: BMS
Jeong Heo - Advisory Committees or Review Panels: Jennerex, Abbvie, Johnson & Johnson; Grant/Research Support: BMS, Roche, GSK; Management Position: Tau PNU Medical
Tae Hun Kim - Grant/Research Support: BMS
Kwan Soo Byun - Advisory Committees or Review Panels: Gilead; Grant/ Research Support: Gilead, BMS, Taiho, Jassen; Speaking and Teaching: BMS
Cyril Llamoso - Employment: Bristol-Myers Squibb
Kyungha Yu - Employment: Bristol-Myers Squibb
The following people have nothing to disclose: Kwan Sik Lee, Young-Oh Kweon, Soon Ho Um, Byung-Ho Kim, Seung Woon Paik, Heon Ju Lee, Dong Joon Kim, Young Sok Lee, Dae-Ghon Kim, Myung Seok Lee, Dong Jin Suh

StephenW

1909

经过240周的治疗，在韩国的患者HBeAg阴性慢性乙型肝炎的疗效与恩替卡韦对战拉米夫定的安全性比较

关锡Lee1，年轻哦Kweon2，不久何UM3，炳浩Kim4，年轻硕Lim5，承焕Paik6，郑某Heo7，宪菊Lee8，东俊Kim9，太浑Kim10，杨索Lee11，关秀Byun12，金大中-Ghon Kim13，明博锡Lee14，西里尔Llamoso15，京荷Yu16，董稽嗯Suh17;

1Gangnam Severance医院，延世大学，首尔，韩国; 2Kyungpook国立大学，大邱，韩国; 3Korea大学安岩医院，首尔，韩国; 4Kyung熙大学医院，庆熙大学，韩国首尔，韩国; 5Asan医疗中心，蔚山，首尔，韩国的大学; 6Samsung医学中心，成均馆大学，首尔，韩国; 7Pusan​​国立大学医院，釜山，韩国; 8Yeungnam大学医学中心，岭南大学医院，大邱，韩国; 9Chuncheon圣心医院，翰林大学，春川，韩国; 10Ewha女子大学木洞医院，Yangchoengu，首尔，韩国; 11Bucheon圣玛丽医院，韩国富川天主教大学，韩国; 12Korea大学九老医院，首尔，韩国; 13Chonbuk国立大学医院，Cheonju，韩国; 14Kang南圣心医院，翰林大学，首尔，韩国; 15Bristol-Myers Squibb公司，沃灵福德，CT; 16Bristol-Myers Squibb公司，首尔，韩国; 17Vievis Namuh医院，首尔，韩国

用途：在抗病毒治疗的患者HBeAg阴性慢性乙型肝炎（CHB）的长期数据是有限的。我们提出的疗效和恩替卡韦（ETV）的安全性与拉米夫定（LAM）相比，在治疗初治的韩国患者的HBeAg阴性CHB超过240周。

方法：患者被随机分配接受ETV0.5 mg /天或林100毫克/期间96周的初始双盲阶段天，随后开放标记治疗通过对周240的主要目的是患者的比例病毒学应答（VR<300拷贝/毫升，通过PCR），在第24周次要目标包括ALT复常（ALT≤1×ULN），并在96周恩替卡韦耐药性的出现，以及患者的VR比例和平均基线HBV减少在整个研究报告的240周的数据安全DNA水平包括不良事件（AE），严重不良事件（严重不良事件），实验室检查异常和中断是由于不良事件。

结果：共120男性和女性患者（>16岁）从14个中心入选韩国各地（ETV，N =56;林，N =64）。有在组（表）之间的基线特征无显着差异。在第24周，患者的VR的比例显著高于教育电视组比LAM组（92.9％对67.2％，P =0.0006），周中96（94.6％对48.4％，P <0.0001），本周240（95.0％对47.6％，P <0.0001）。在96周，ALT正常化中观察到的ETV处理的87.5％和51.6％，林治疗的患者（P <0.0001），同时接收病毒学突破发生1例（1.8％）接受ETV和26例（42.6％）林（P <0.0001）。未检测到抗ETV的出现。平均减少HBV DNA从基线到240周是-3.61±0.76和-2.45±1.54 log10拷贝/毫升的ETV和LAM，分别为（P <0.0001）。总体而言，11个严重不良事件报告了7 ETV治疗的患者中，20人严重不良事件报告17 LAM治疗的患者（P=0.055）;然而，这些事件是不相关的任一所述的研究药物。

结论：长期治疗ETV提供优于LAM，HBeAg阴性慢性乙肝患者获得病毒学应答和ALT复常的显著比例较高。两种治疗的耐受性良好。

表。基线数据和VR

披露：

年轻的淑林 - 格兰特/研究支持：BMS

郑许 - 咨询委员会或审查小组：Jennerex，Abbvie，强生;格兰特/研究支持：BMS，罗氏，葛兰素史克，管理您的位置：头PNU医疗

太浑金 - 格兰特/研究支持：BMS

关秀卞 - 咨询委员会或审查小组：基列;格兰特/研究支持：Gilead公司，BMS，大鹏，雅森;说起与教学：BMS

西里尔Llamoso - 就业：百时美施贵宝

京荷玉 - 就业：百时美施贵宝

下面的人都没有透露：关锡利扬哦Kweon，不久何庵，炳浩金升焕白南准，宪菊李，董浚金，杨索利，大亚Ghon金，明博锡利，董击嗯徐

1909 Nián