AASLD2007:恩替卡韦治疗HBeAg(+)初治者最新4年数据----百济新特药房肝病专科

恩替卡韦（博路定）治疗HBeAg(+)初治者4年里保持对乙肝病毒的持续抑制

在为期四年的队列研究中，91 ％的博路定® （恩替卡韦）治疗患者，实现HBV-DNA转阴。

抗药性检测显示：在进行研究的所有HBeAg(+)慢性乙肝初治者中，只有1例患者出现了对博路定（恩替卡韦）的基因耐药。

几种新的抗病毒化合物已被批准用于治疗慢性乙型肝炎，其中包括核苷类似物恩替卡韦（博路定），这为初治者及拉米夫定耐药的乙肝患者提供了更多选择。

最近，在波士顿举行的第58届美国肝病研究学会年会（AASLD 58th. 2007年11月2-6日）上公布的一项最新研究表明：在使用恩替卡韦192周后，有91%的患者HBV病毒载量下降到探测不到的水平。病毒载量低于检测水平是抗病毒治疗应答的一个标准，同时保持病毒抑制是慢性乙型肝炎治疗的一个重要目标。

这份4年队列研究的对象，是以前没有经过核苷类药物治疗且e抗原为阳性的慢性乙肝患者。HBeAg是一种病毒蛋白，它是乙肝病毒复制活跃的标志。在研究ETV-022中，患者初始治疗给于恩替卡韦0.5mg/d，而另一项研究ETV-901，患者经过一个35天或更少的治疗缺口后，给于恩替卡韦1.0mg/d继续治疗。

结果：

• 在第192周，91%（98/108）的患者实现了病毒载量低于检测水平(HBV DNA < 300 copies/mL)。
• 86%(96/112)的患者ALT水平恢复正常(ALT <1UNL)。
• 在治疗的第3和第4年，有41%的患者（39/96）实现了HbeAg转阴，且有16%的患者（15/96）达到了HBeAg血清转换。
• 抗药性检测发现了1例患者对恩替卡韦基因耐药，并接着出现了病毒学突破。
• 不良事件的发生与以往试验一致。
• 4年队列研究中，患者的其他累计安全结果报告如下：
    -90%的患者未发生不良事件
    -报道的3-4级不良事件发生率为13%
    -没有患者因不良事件而中断试验
    -在治疗的第4年中，只有低于1%的患者出现了ALT增高。

根据这些结果，研究者总结说： “截至到第192周，在接受接受恩替卡韦治疗四年的患者中，HBV DNA转阴率为91%，ALT复常率为86%，且在第3到第4年中，继续有患者实现HBeAg转阴和HBeAg血清转化。药物安全性与先前试验报道一致” 。

“数据显示，通过四年的治疗，博路定保持对病毒的持续抑制，”巴西愉港市南大河联邦大学的医学博士，此项研究的作者之一 Hugo Cheinquer说：“在4年的研究中，多数博路定的病人病毒载量低于检测水平，只有一名患者出现了耐药，这对医师治疗这种顽症是一个很大的鼓舞。”

Entecavir (Baraclude) Maintains HBV Suppression through 4 Years in Nucleoside-naive HBeAg Positive Patients

Several new antiviral compounds have been approved for the treatment of chronic hepatitis B, including the nucleoside analog entecavir (Baraclude), offering more choices for treatment-naive patients and for those who have developed resistance to lamivudine (Epivir-HBV),

Results of the current study, presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007) in Boston (November 2-6, 2007), demonstrated that 91% of patients treated with entecavir achieved undetectable HBV viral load at week 192. Undetectable viral load is a measure of antiviral treatment response, and maintenance of viral suppression is an important goal of chronic hepatitis B treatment.

Participants in this 4-year cohort study had chronic HBV infection, were hepatitis B "e" antigen (HBeAg) positive, and had not previously been treated with nucleosides. HBeAg is a viral protein identified as a marker of active replication of HBV. Patients were initially treated with 0.5 mg entecavir in study ETV-022 and continued treatment with 1 mg entecavir by enrolling in study ETV-901 with a treatment gap of 35 days or less.

Results

• At week 192, 91% of patients (98 of 108) achieved undetectable HBV viral load (HBV DNA < 300 copies/mL).

• 86% of patients (96 of 112) achieved ALT normalization (ALT <1 times the upper limit of normal [ULN]).

• During years 3 and 4, an additional 41% of patients (39 of 96) lost HBeAg and 16% (15 of 96) achieved HBeAg seroconversion.

• Resistance monitoring identified 1 patient with genotypic resistance to entecavir who later experienced viral breakthrough.

• Adverse events were consistent with previous experience.

• Additional cumulative safety results of patients reported in this 4-year cohort:

- 90% of patients had no adverse events.

- Grade 3-4 adverse events were reported in 13%.

- There were no discontinuations due to adverse events.

- Less than 1% experienced on-treatment ALT flares during the fourth year.

Based on these results, the researchers concluded, "At Week 192, 91% of patients who received entecavir treatment during 4 years achieved undetectable HBV DNA and 86% had ALT normalization, with patients continuing to experience HBeAg loss and HBeAg seroconversion during Years 3 and 4. The safety profile was consistent with previously reported experience."

"The data indicate that Baraclude maintained viral suppression through 4 years of treatment in this patient population," said study co-author Hugo Cheinquer, MD, of Universidad Federal Do Rio Grande Do Sul, Porto Alegre, Brazil. "That a majority of Baraclude patients had undetectable viral load at 4 years with 1 patient developing resistance is very encouraging news for physicians who treat this chronic disease."

Endpoint Week 192

HBV DNA <300 copies/mL 98/108 (91%)

ALT < 1 x ULN 96/112 (86%)

HBeAg loss 39/96 (41%)

HBeAg seroconversion 15/96 (16%)

Division of Digestive Disease, UCLA School Of Medicine, Los Angeles, CA; National Cheng Kung University Medical College, Tainan, Taiwan; Tri-Service General Hospital, Taipei, Taiwan; Kangnam St. Mary's Hospital, Soeul, South Korea; California Pacific Medical Center, San Francisco, CA; Universidad Federal Do Rio Grande Do Sul, Porto Alegre, Brazil; Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo, Brazil; Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT.

11/06/07

Reference

S Han, T Chang, Y Chao, and others. Four-Year Entecavir Treatment in Nucleoside-Naive HBeAg(+) Patients: Results from Studies ETV-022 and -901 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA. November 2-6, 2007. Abstract 938.