AASLD 2021：乙型肝炎疫苗 HepB-CpG 在慢性肝病方面证明优于 HepB-

StephenW

AASLD 2021：乙型肝炎疫苗 HepB-CpG 在慢性肝病方面证明优于 HepB-ENG

在慢性肝病中优于 HepB-ENG，观察到显着更高的血清保护率。

实践更新编辑团队

Kelvin McKoy，医学博士，MBA

2021 年 11 月 12 日——弗吉尼亚州亚历山大市——在慢性肝病患者中，乙型肝炎疫苗 HepB-CpG 的血清保护率明显高于 HepB-ENG。 11 月 12 日至 15 日，在美国肝病研究协会 (AASLD) 的 2021 年虚拟肝脏会议上报告了对三个 3 期、随机、观察者盲法、临床试验的汇总事后分析的结果。

加利福尼亚州伯克利 Dynavax Technologies Corporation 的医学博士、工商管理硕士 Kelvin McKoy 及其同事着手通过汇总和分析来自三项试验的数据来比较两种疫苗。

“我们进行了这项研究，”McKoy 博士告诉 Elsevier's PracticeUpdate，“以进一步评估 HEPLISAV-B 与 Engerix-B 在对常规三剂乙型肝炎疫苗的反应趋于减弱的一部分患者中的安全性和免疫原性.这些试验在 13,241 名 18 - 70 岁的成年人中进行，并比较了两种总剂量的 HEPLISAV-B）（20 微克 rHBsAg + 3000 微克 CpG 1018 佐剂）与三种总剂量的 Engerix-B（20 微克 rHBsAg） + 0.5 mg 明矾佐剂）。

McKoy 博士指出，“toll 样受体 9 激动剂 CpG 1018 是一种高免疫原性佐剂，其安全性与 Engerix-B 相似。 CpG 1018 为百日咳、带状疱疹和流感等其他疾病状态提供了潜在的希望。”

HEPLISAV-B 在第 0 周和第 4 周（安慰剂在第 24 周）给药。 Engerix-B 在第 0、4 和 24 周给药。慢性肝病患者通过病史或不良事件中的实质肝病的首选术语来确定。在对三项试验的改良意向治疗人群的汇总事后分析中，比较了慢性肝病患者的峰值血清保护率（抗 HBs ≥ 10 mIU/mL 的最高百分比）。

在改良意向治疗人群的 12,728 名受试者中，350 名 (2.7%) 有慢性肝病病史或不良事件：

    n=272 HepB-CpG
    n=78 HepB-Eng

最常见的诊断是：

    n=102 肝脂肪变性
    n=47 丙型肝炎
    n=7 肝硬化

基线时的疫苗组是平衡的，并具有以下特点：

    平均年龄 51.8 岁
    56.3% 男性
    87.4% 白
    8.6% 黑色
    2.9% 亚洲人
    15.3% 西班牙裔

HepB-CpG 的血清保护率 (92.6% [95% 置信区间 88.9, 95.5]) 在统计学上显着高于 HepB-Eng (74.4% [95% 置信区间 63.2, 83.6]; P < .0001)。

HepB-CpG 乙型肝炎表面抗体的几何平均浓度 (258.0 mIU/mL [95% 置信区间 204.5, 325.5]) 在统计学上显着高于 HepB-Eng (134.7 mIU/mL [95% 置信区间 68.1, 266.4] ]；P = .02)。

在肝脂肪变性患者中，HepB-CpG 的血清保护率（87.4% [76 of 87]）在统计学上显着高于 HepB-Eng（68.0% [17 of 25]，P = .04）。

HepBCpG 和 HepB-Eng 的安全性相似。

McKoy 博士解释说，建议慢性肝病患者接种乙型肝炎疫苗，因为该人群因乙型肝炎病毒感染而出现严重后果的风险较高。此外，据报道，慢性肝病患者对明矾佐剂的乙型肝炎疫苗的免疫反应降低。他得出的结论是，HepB-CpG 给予超过 1 个月的两剂给药方案与超过 6 个月的 HepB-Eng 三剂给药方案相比具有优势。在慢性肝病患者中，HepB-CpG 也显示出比 HepB-Eng 显着更高的血清保护率。

McKoy 博士说：“结果值得注意，因为它们支持并建立在第三个关键的 3 期试验的结果之上。后者还在更大的患者队列中评估了 HEPLISAV-B 与 Engerix-B 的安全性和免疫原性，这些患者往往对传统的三剂乙型肝炎疫苗反应不佳。这项更大的试验包括老年患者、糖尿病患者、吸烟者和体重指数较高的患者。

*目前的结果，”他继续说，“与同行评审的已发表研究一致，在这些研究中，两剂 HEPLISAV-B 方案与三剂 Engerix-B 方案相比，在所有患者类型中表现出更快和更高的血清保护率。”

最后，McKoy 博士断言，“HEPLISAV-B 具有未来的、令人信服的影响，特别是考虑到免疫实践咨询委员会最近投票决定 19-59 岁的人应该接种疫苗。那些年龄≥60 岁且有乙型肝炎危险因素的人也应该接种疫苗。没有乙肝风险因素的 60 岁以上的人可以接种疫苗。”

StephenW

AASLD 2021: The Hepatitis B Vaccine HepB-CpG Proves Superior to HepB-ENG in Chronic Liver Disease

Superior to HepB-ENG in Chronic Liver Disease, significantly higher rates of seroprotection were observed.

PracticeUpdate Editorial Team

Kelvin McKoy, MD, MBA

November 12, 2021—Alexandria, Virginia—Significantly higher rates of seroprotection have been observed with the hepatitis B vaccine HepB-CpG than with HepB-ENG in patients with chronic liver disease. This outcome of a pooled post hoc analysis of three phase 3, randomized, observer-blind, clinical trials was reported at the 2021 virtual Liver Meeting of the American Association for the Study of Liver Diseases (AASLD), from November 12 – 15.

Kelvin McKoy, MD, MBA, of Dynavax Technologies Corporation, Berkeley, California, and colleagues set out to compare the two vaccines by pooling and analyzing data from the three trials.

“We undertook the study,” Dr. McKoy told Elsevier’s PracticeUpdate, “to further assess the safety and immunogenicity of HEPLISAV-B vs Engerix-B in a subset of patients whose responses to conventional three-dose hepatitis B vaccines tends to be e attenuated. The trials had been conducted in 13,241 adults 18 - 70 years of age and compared two total doses of HEPLISAV-B) (20 μg of rHBsAg + 3000 μg of CpG 1018 adjuvant) vs three total doses of Engerix-B (20 μg of rHBsAg + 0.5 mg alum adjuvant).

Dr. McKoy noted, “The toll-like receptor 9 agonist CpG 1018 is a highly immunogenic adjuvant with a safety profile similar to Engerix-B. CpG 1018 offers potential promise in other disease states such as pertussis, zoster, and influenza.”

HEPLISAV-B was administered at 0 and 4 weeks (placebo at 24 weeks). Engerix-B was administered at 0, 4, and 24 weeks. Patients with chronic liver disease were identified by preferred termsindicative of parenchymal liver disease in medical history or adverse events. Peak seroprotection rates (highest percentage with anti-HBs ≥ 10 mIU/mL) in patients with chronic liver disease were compared in a pooled post hoc analysis of the modified intent-to-treat populations of the three trials.

Of the 12,728 subjects in the modified intent-to-treat population, 350 (2.7%) had a history or adverse event of chronic liver disease:

    n=272 HepB-CpG
    n=78 HepB-Eng

The most frequent diagnoses were:

    n=102 hepatic steatosis
    n=47 hepatitis C
    n=7 cirrhosis

Vaccine groups at baseline were balanced, and were characterized by the following:

    Mean age 51.8 years
    56.3% men
    87.4% white
    8.6% black
    2.9% Asian
    15.3% Hispanic

The seroprotection rate with HepB-CpG (92.6% [95% confidence interval 88.9, 95.5]) was statistically significantly higher than with HepB-Eng (74.4% [95% confidence interval 63.2, 83.6]; P < .0001).

Geometric mean concentrations of hepatitis B surface antibody with HepB-CpG (258.0 mIU/mL [95% confidence interval 204.5, 325.5]) were statistically, significantly higher than with HepB-Eng (134.7 mIU/mL [95% confidence interval 68.1, 266.4]; P = .02).

In patients with hepatic steatosis, the seroprotection rate with HepB-CpG (87.4% [76 of 87]) was statistically significantly higher than with HepB-Eng (68.0% [17 of 25], P = .04).

The safety profiles of HepBCpG and HepB-Eng were similar.

Dr. McKoy explained that hepatitis B vaccines are recommended in patients with chronic liver disease because this population is at higher risk of severe outcomes from hepatitis B virus infection. Additionally, patients with chronic liver disease have been reported to exhibit reduced immune responses to alum-adjuvanted hepatitis-B vaccines. He concluded that HepB-CpG confers an advantageous two-dose-regimen given over 1 month vs the three-dose regimen of HepB-Eng given over 6 months. HepB-CpG was also shown to induce statistically significantly higher rates of seroprotection than HepB-Eng in patients with chronic liver disease.

Dr. McKoy said, “The results are noteworthy inasmuch as they support and build on results of the third pivotal, phase 3 trial. The latter also assessed the safety and immunogenicity of HEPLISAV-B vs Engerix-B in a larger cohort of patients who tend to hyporespond to traditional three-dose hepatitis B vaccines. This larger trial included older patients, diabetics, smokers, and patients with higher body mass index.

*The present results,” he continued, “are consistent with peer-reviewed, published studies in which a two-dose regimen of HEPLISAV-B demonstrated faster and higher rates of seroprotection vs a three-dose Engerix-B regimen across all patient types.”

Finally, Dr. McKoy asserted, “HEPLISAV-B holds future, compelling implications, particularly in light of the recent vote by the Advisory Committee on Immunization Practices to from age 19 - 59 years should be vaccinated. Those age ³60+ years with risk factors for hepatitis B should also be vaccinated. Individuals ³60 years of age without risk factors for hepatitis B may be vaccinated.”