AASLD2020[772]HEPLISAV-B的安全性和免疫性 怀孕

StephenW

772
SAFETY AND IMMUNOGENICITY OF HEPLISAV-B IN
PREGNANCY
Tatyana Kushner1, John Youhanna2, Robert Walker2, Kimberly
Erby2 and Robert S. Janssen3, (1)Division of Liver Diseases,
Icahn School of Medicine, Mount Sinai Hospital, (2)Dynavax
Technologies, (3)Dynavax Technologies Corporation
Background: HEPLISAV-B® [hepatitis B vaccine
(recombinant), adjuvanted] has recently been approved for
use in adults age 18 and over HEPLISAV-B was evaluated in
11 clinical trials, 7 of which were head-to-head comparisons
to Engerix-B® HEPLISAV-B demonstrated statistically
significantly higher seroprotection rates (SPRs), and similar
safety However, there are no published data available
regarding the safety and immunogenicity of HEPLISAV-B
during pregnancy As pregnancy was an exclusion criterion
for trial enrollment, we evaluated outcomes in women
who became pregnant during participation in the clinical
development program Methods: Retrospective analysis of
women enrolled in the HEPLISAV-B clinical trials who had
pregnancy documented during trial participation and follow up
The last menstrual period (LMP) recorded was compared to
timing of last dose of vaccine. Seroprotection was defined as
anti-HBs≥10mIU/mL and confidence intervals were calculated
using the Clopper Pearson method Results:: Among 7340
female subjects enrolled, we identified pregnancies in
40/5145 (0 78%) women who received HEPLISAV-B and in
19/2195 (0 87%) who received Engerix-B Among pregnant
women in both groups, median age (30 5 versus 31 0),
race (73% versus 63% white; 20% versus 26 3% black),
and ethnicity (12 5% versus 10 5% Hispanic), were similar
Median time from last HBV vaccine dose to last menstrual
period (LMP) was 81 days (Interquartile Range, IQR: 30, 219)
in HEPLISAV-B recipients and 42 days (IQR: 14, 98) in the
Engerix-B arms Seroprotection rates were 28/28 (100%; 95%
CI: 87 7%-100 0%) at 24 weeks of follow-up for HEPLISAV-B
versus 8/14 (57 1%; 95% CI: 28 9%-82 3%) at 28 weeks in
the Engerix-B arms In the HEPLISAV group, peak anti-HBs
levels were ≥ 10 IU/L and < 100 IU/L in 4/40 (10%) subjects
and ≥100 in 34/40 (85%), compared to 4/19 (21%) and 10/19
(53%), respectively, in the Engerix-B arms 2 (5%) in the
HEPLISAV-B arm versus 7 (37%) in the Engerix-B arms were
vaccine non-responders (i e peak recorded anti-HBs level
<10 IU/L) Rates of pregnancy outcomes included 24 (60%)
versus 11 (55%) healthy term deliveries, 3 (7 5%) vs 2 (10%)
spontaneous abortions, 1 (2 5%) versus 1 (5%) congenital
anomaly, 2(5%) versus 2 (10%) elective terminations, 2 (5 0%)
versus 0 preterm deliveries, and 1(2 5%) versus 0 stillbirths,
in the HEPLISAV-B versus the Engerix-B arms (see Figure
1 for data on outcomes and peak HBsAg titers in all women
with available LMP data) Conclusion: These data from the
clinical development program show HEPLISAV-B in pregnant
women to induce higher rates of immunogenicity over a
shorter dosing regimen with similar fetal outcomes compared
with Engerix-B. These results should be further verified with
additional studies or data to confirm the safety and efficacy of
HEPLISAV-B in pregnant women.

StephenW

772
乙型肝炎病毒B的安全性和免疫性
怀孕
Tatyana Kushner1，John Youhanna2，Robert Walker2，Kimberly
Erby2和Robert S.Janssen3，（1）肝病科，
西奈山医院伊坎医学院，（2）Dynavax
Technologies，（3）Dynavax Technologies Corporation
背景：HEPLISAV-B®[乙型肝炎疫苗
（重组），佐剂]最近被批准用于
评估了18岁及以上HEPLISAV-B成年人的使用情况
11项临床试验，其中7项进行了正面对比
对Engerix-B®HEPLISAV-B进行统计证明
血清保护率（SPRs）明显更高，并且类似
安全性但是，没有可用的公开数据
关于HEPLISAV-B的安全性和免疫原性
怀孕期间由于怀孕是一项排除标准
对于试验入组，我们评估了女性的结局
在参加临床试验期间怀孕的人
开发程序方法：回顾性分析
参加HEPLISAV-B临床试验的女性
在试验参与和随访期间记录妊娠
将上次记录的月经期（LMP）与
最后一剂疫苗的时间安排。血清保护定义为
计算抗HBs≥10mIU/ mL和置信区间
使用Clopper Pearson方法结果：:在7340中
女性受试者入组后，我们确定了
40/5145（0 78％）妇女曾接受HEPLISAV-B并接受
19/2195（0 87％）在孕妇中接受Engerix-B的人
两组中的女性，中位年龄（30 5比31 0），
种族（73％对63％白人； 20％对26 3％黑人），
和种族（12 5％对10 5％西班牙裔）相似
从上次HBV疫苗接种到最后一次月经的中位时间
周期（LMP）为81天（四分位间距，IQR：30，219）
在HEPLISAV-B接受者中，在42天（IQR：14，98）在
Engerix-B武器的血清保护率是28/28（100％; 95％
CI：HEPLISAV-B随访24周时为87 7％-100 0％）
相比于28周时的8/14（57 1％; 95％CI：28 9％-82 3％）
Engerix-B组在HEPLISAV组中，抗HBs达到峰值
4/40（10％）受试者的水平≥10 IU / L≤100 IU / L
和34/40（85％）中的≥100，而4/19（21％）和10/19
（53％）分别在Engerix-B第2组（5％）
HEPLISAV-B组与Engerix-B组中的7种（37％）
疫苗无反应者（即记录的最高抗HBs水平
<10 IU / L）的妊娠结局率包括24（60％）
相比健康期分娩为11（55％），3（7 5％）对2（10％）
自发性流产，先天性流产1（2 5％）对1（5％）
异常，2（5％）对2（10％）选择性终止，2（5 0％）
相对于0个早产，以及1（2 5％）与0个死胎，
在HEPLISAV-B与Engerix-B臂中（参见图
1用于所有妇女的结局和HBsAg峰值滴度数据
包含可用的LMP数据）结论：这些数据来自
临床开发计划显示孕妇HEPLISAV-B
妇女在一个以上的时间里诱导更高的免疫原性
与胎儿结果相似的较短给药方案
与Engerix-B。这些结果应进一步验证
其他研究或数据，以确认安全性和有效性
孕妇使用HEPLISAV-B。