AASLD2019[193]切换或添加聚乙二醇干扰素治疗慢性肝炎 B病人已

StephenW

SWITCH OR ADD-ON PEGINTERFERON TO CHRONIC HEPATITIS
B PATIENTS ALREADY ON NUCLEOS(T)IDE ANALOGUE
THERAPY (SWAP STUDY): FINAL RESULTS
Seng Gee Lim1, Wei Lyn Yang2, Jason Pik Eu Chang3, Jeffrey
Ngu4, Yi -Lyn Jessica Tan5, Taufique Ahmed6, Yock Young
Dan7, Yin Mei Lee8, Guan Huei Lee8, Poh Seng Tan9, Wah
Wah Phyo10, Lay Wai Khin11, Chris Lee10, Amy Tay10 and Edwin
Chan12, (1)Gastroenterology & Hepatology, National University
Health System, (2)Dept of Gastroenterology, Tan Tock Seng
Hospital, (3)Duke-Nus Medical School, Singapore, (4)Dept
of Gastroenterology, Singapore General Hospital, (5)Dept of
Gastroenterology, Changi General Hospital, (6)Jerudong Park
Medical Centre, (7)Division of Gastroenterology & Hepatology,
National University Health System, Singapore, (8)Division of
Gastroenterology & Hepatology, National University Health
System, (9)Division of Gastroenterology and Hepatology,
National University Health System, Singapore, (10)Dept of
Medicine, Yong Loo Lin School of Medicine, (11)Perinatal
Audit and & Epidemiology Unit, Kandang Kerbau Hospital,
(12)Duke-Nus School of Medicine
Background: It is unclear whether add-on or switch to
peginterferon alpha (PEG) in patients on long term nucleos(t)
ide analogue (NA) therapy is more efficacious for HBsAg
loss, hence we conducted a randomised control trial(RCT) to
address this Methods: This was a multicentre RCT of addon[
AO] or switch[S] to PEG(pegintron, Merck, USA) for 48
weeks, versus continuing NA randomised 2:2:1 (clinicaltrial.
gov NCT01928511). Patients were enrolled from five public
hospitals in Singapore, approved by IRB(DSRB2012/01039)
Computer randomisation stratified patients by HBeAg status,
high/low genetic barrier NA, or fibroscan score. Eligibility:
HBsAg>6months, NA>12 months, compensated cirrhosis
and undetectable HBVDNA. Exclusions: telbivudine,
decompensated cirrhosis, significant co-morbidities. The
primary endpoint was a composite of qHBsAg>1log reduction
or HBeAg loss, and secondary endpoint was HBsAg loss
at week 72 A study size of 255 patients had a 80% power
to detect a 30% difference between AO/S versus NA
Analysis was by intention-to-treat(ITT) using SPSSv20
Results: A total of 253 (AO 78, S 79, NA 42) patients were
randomised. ITT analysis at week 72, found qHBsAg>1 log
(IU/ml) reduction in 18/99(18%) in AO, 21/103 (20%) in S
and 1/51(2%) in NA(p<0 05 vs NA) HBeAg loss occured in
5/29 (17%) in AO arm, 11/37 (30%) in S and 0% in NA(p=ns)
The primary endpoint occured in 31/99 (31%) in AO, 35/103
(34%) in S and 1/51(2%) in NA (p<0 0001 vs NA) HBsAg
loss was seen in 9/99 (10%)in AO, 8/103 (8%) in S and 0%
in NA (p=0 026 AO vs NA, p=0 041 S versus NA) Baseline
qHBsAg[bqHBsAg]<48IU/ml was a predictor of HBsAg loss
for AO while S had higher bqHBsAg <310 IU/ml as a predictor
of HBsAg loss (p=0.026). HBV reactivation was seen in 16/53
(30 2%) in S 1/51 (2%) in AO and 1/30 (3 3%) NA(p<0 004
in S vs AO or NA) On multivariate analysis, bqHBsAg(logIU/
ml),week 8 qHBsAg log difference from baseline, and
age were independent predictors of HBsAg loss with
AUROC=0 96 (0 93-0 997),p<0 001 There were 38(15 0%)
discontinuations/withdrawals during therapy(11 from adverse
events[AE]) 1511AEs, 14serious adverse events. There was
one death due to myocardial infarction The most common
AEs were interferon-related Conclusion: Final results of the
SWAP study showed no significant difference between S and
AO to NA, with bqHBsAg, week 8 qHBsAg difference and age
being independent predictors However, AO required a much
lower bqHBsAg to achieve HBsAg loss compared to S.

StephenW

切换或添加聚乙二醇干扰素治疗慢性肝炎
B病人已经使用核苷类似物
治疗（交换研究）：最终结果
Seng Gee Lim1，Wei Lyn Yang2，Jason Pik Eu Chang3，Jeffrey
Ngu4，Yi -Lyn Jessica Tan5，Taufique Ahmed6，Yock Young
Dan7，Yin Mei Lee8，Guuan Huei Lee8，Poh Seng Tan9，Wah
Wah Phyo10，Lay Wai Khin11，Chris Lee10，Amy Tay10和Edwin
Chan12，（1）国立大学胃肠病学和肝病学
卫生系统，（2）谭笃生消化内科
医院，（3）新加坡杜克努斯医学院，（4）
新加坡总医院消化内科（5）
樟宜总医院消化内科（6）Jerudong Park
医疗中心，（7）胃肠病和肝病科，
新加坡国立大学卫生系统，（8）
国立大学卫生部胃肠病学和肝病学
系统，（9）胃肠病学和肝病学，
新加坡国立大学卫生系统（10）
Yong Loo Lin医学院医学，（11）围产期
关丹克尔鲍医院审计与流行病学科
（12）杜克-努斯医学院
背景：目前尚不清楚附加还是切换到
长期接受核仁治疗的患者中的聚乙二醇干扰素α（PEG）
Ide类似物（NA）治疗对HBsAg更有效
损失，因此我们进行了一项随机对照试验（RCT）
解决此方法：这是插件的多中心RCT [
AO]或将[S]切换为PEG（pegintron，默克公司，美国）48
周，而不是连续NA：2：2：1（临床试验。
政府NCT01928511）。患者来自五个公众
IRB批准的新加坡医院（DSRB2012 / 01039）
计算机随机化按HBeAg状态对患者进行分层，
高/低遗传屏障NA或纤维扫描评分。合格：
HBsAg> 6个月，NA> 12个月，代偿性肝硬化
和无法检测到的HBVDNA。排除：替比夫定，
代偿性肝硬化，合并症明显。的
主要终点是qHBsAg> 1log降低的复合
或HBeAg丢失，而次要终点为HBsAg丢失
在第72周时，一项255名患者的研究规模具有80％的功效
检测AO / S与NA之间的30％差异
使用SPSSv20通过意向性治疗（ITT）进行分析
结果：共253例（AO 78，S 79，NA 42）患者
随机化。第72周的ITT分析发现qHBsAg> 1 log
（IU / ml）在AO中减少18/99（18％），在S中减少21/103（20％）
NA中有1/51（2％）（p <0 05 vs NA）发生了HBeAg丢失
AO臂为5/29（17％），S为11/37（30％），NA为0％（p = ns）
主要终点在AO（35/103）中以31/99（31％）被杀死
S（34％）和NA中的1/51（2％）（p <0.0001 vs NA）HBsAg
AO的损失为9/99（10％），S的损失为8/103（8％），0％
在NA中（p = 0 026 AO对NA，p = 0 041 S对NA）基线
qHBsAg [bqHBsAg] <48IU / ml是HBsAg丢失的预测指标
对于AO而S具有较高的bqHBsAg <310 IU / ml作为预测因子
HBsAg丢失（p = 0.026）。在16/53中发现HBV重新激活
（30 2％）的S 1/51（2％）的AO和1/30（3 3％）NA（p <0004）
在S vs AO或NA中）在多变量分析中，bqHBsAg（logIU /
M1），第8周与基线的qHBsAg对数差异，以及
年龄是HBsAg丢失的独立预测因素
AUROC = 0 96（0 93-0 997），p <0 001共有38（15 0％）
治疗期间停药/停药（不良反应11
事件[AE]）1511AEs，14例严重不良事件。有
心肌梗死致死最常见
不良事件是与干扰素有关的结论。
SWAP研究表明S与S之间无显着差异
AO至NA，伴bqHBsAg，第8周qHBsAg差异和年龄
成为独立的预测器但是，AO需要付出很多努力
与S相比，降低bqHBsAg以达到HBsAg损失。