AASLD2014:恩替卡韦加替诺福韦联合治疗的患者多药耐药的慢性

StephenW

1865
Entecavir Plus Tenofovir Combination Therapy in Patients with Multi-drug Resistant Chronic Hepatitis B: The 48-Week Results of A Multicenter, Prospective Study
Jun Yong Park1, Chang Wook Kim2, Si Hyun Bae2, Sang Hoon Ahn1;
1Department of Internal Medicine, Yonsei Univ, Seoul, Republic of Korea; 2Department of Internal Medicine, The Catholic University College of Medicine, Seoul, Republic of Korea

Background: Sequential therapy particularly with drugs with low barrier to resistance posed a high risk of emergence of multi-drug resistance (MDR) and presented a management issue and unmet need in chronic hepatitis B (CHB) treatment. We evaluated the antiviral efficacy and safety of entecavir (ETV) plus tenofovir (TDF) combination therapy in patients with MDR CHB.
Methods: In this prospective, multicenter study, patients with MDR CHB, defined as measurable serum HBV DNA (≥ 60 IU/mL) while on any rescue treatment regimen for at least 24 weeks and the presence of documented genotypic resistance to both nucleoside analogue(s) and nucleotide analogue at any previous time, were treated with ETV 1.0mg and TDF 300mg combination therapy for 48 weeks.
Results: Of the 73 consecutive patients screened in this study, a total of 64 eligible patients, who had previously failed to a median three lines of antiviral therapy (range 2-6), were included. At baseline, median age was 47.0 years, 80.8% were male, 89.1% were HBeAg(+), median HBV DNA was 4.24 (range 2.11-6.73) log10 IU/ml, and mean ALT was 39.7 IU/ml. By week 4, 12, 24 and 48, 15/64 (23.4%), 36/64 (56.3%), 43/64 (67.2%) and 56/63 (85.9%) patients achieved a HBV DNA < 60 IU/ml, respectively. The median reduction of HBV DNA from baseline to 4 weeks and 48 weeks was 1.23 log10 IU/ml and 2.39 log10 IU/ml, respectively. Although 5 patients experienced virological breakthrough, all were transient and no additional/novel mutation was detected in any patients. Two patients lost HBeAg, but no HBeAg seroconversion was observed for 48 weeks. ETV plus TDF combination therapy was well tolerated, and no clinical significant adverse events were noticed during the study period.
Conclusions: Our results show that, in difficult-to-treat MDR CHB patients with a high exposure to multiple antiviral drugs, ETV plus TDF combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.

Disclosures:

Chang Wook Kim - Consulting: Gilead, MSD; Grant/Research Support: BMS, Handok, Pharmicell, Pharmaking; Speaking and Teaching: BMS, Donga, Daewoong

The following people have nothing to disclose: Jun Yong Park, Si Hyun Bae, Sang Hoon Ahn

StephenW

1865
恩替卡韦加替诺福韦联合治疗的患者多药耐药的慢性乙型肝炎的多中心，前瞻性研究的48周结果
君永Park1，昌旭Kim2，思玄Bae2，桑勋Ahn1;
教研室内科，延世大学，首尔，韩国的;内科，医学天主教大学，韩国首尔的教研室

背景：序贯疗法特别是药物与低耐药屏障所带来的多药耐药（MDR）的出现的高风险，并提出了管理问题，未满足的需求在慢性乙型肝炎（CHB）治疗。我们评估的抗病毒疗效和恩替卡韦（ETV）加替诺福韦（TDF）联合治疗的安全性患者多药耐药慢性乙型肝炎。
方法：采用前瞻性，多中心的研究中，患者多药耐药慢性乙型肝炎，定义为可测量的血清HBV DNA（≥60国际单位/毫升），而在任何抢救治疗方案至少24周的记录基因型耐药性既核苷类似物的存在（ S）和核苷酸类似物，在以往任何时候，均采用恩替卡韦1.0毫克和300毫克的TDF联合治疗48周。
结果：73例患者中筛选在本研究中，总共64个符合条件的患者，谁以前没有中位数三行抗病毒治疗（范围2-6）的，都包括在内。在基线，平均年龄为47.0年中，80.8％是男性，89.1％为HBeAg（+），HBV DNA中位数为4.24（范围2.11-6.73）日志10 IU / ml，并将平均ALT为39.7 IU /毫升。 4周，12，24和48，15/64（23.4％），36/64（56.3％），43/64（67.2％）和56/63（85.9％）患者达到HBV DNA<60 IU/毫升。位数减少HBV DNA的从基线至4周和48周为1.23日志10 IU / ml和2.39日志10 IU /毫升。虽然5例患者发生病毒学突破，均为暂时性，在任何患者未检测到额外的/新的突变。两名患者HBeAg消失，但观察48周无HBeAg血清学转换。恩替卡韦加华盈联合治疗的耐受性良好，并且在研究期间没有临床显著不良反应注意。
结论：我们的研究结果表明，在难以治疗耐多药CHB患者具有高接触多种抗病毒药物，恩替卡韦加华盈联合治疗可至48周的治疗提供病毒抑制率非常高。

披露：

昌旭金 - 咨询：Gilead公司，MSD;格兰特/研究支持：BMS，Handok，Pharmicell，Pharmaking;口语和教学：BMS，东阿，大雄

下面的人都没有透露：勇俊园，思玄裴，桑勋安