AASLD2020[19] 使用或隨機化192週的替諾福韋試驗 前24週沒有PEG干

StephenW

19
RANDOMIZED TRIAL OF 192 WEEKS OF TENOFOVIR WITH OR
WITHOUT PEGINTERFERON ALFA FOR THE FIRST 24 WEEKS
FOLLOWED BY PROTOCOLIZED WITHDRAWAL IN ADULTS
WITH CHRONIC HEPATITIS B
Norah Terrault1,2, Anna S. Lok3, Abdus Wahed4, David
Kh Wong5, Mandana Khalili6, Michael W Fried7, Daryl
Lau8, Marc G. Ghany9, Richard K. Sterling10, Adrian M Di
Bisceglie11, Robert P. Perrillo12, Mauricio Lisker-Melman13,
Stewart Cooper14, Raymond T. Chung15, Keyur Patel16, Lewis
R. Roberts17, Charles Landis18, Mohamed A. Hassan19,
Christopher A. Aoki20, Steve Belle21 and Harry L.A. Janssen16,
(1)Division of Gastrointestinal and Liver Diseases, University
of Southern California, (2)GI and Liver Diseases, University
of Southern California, (3)University of Michigan, (4)School
of Public Health, University of Pittsburgh, (5)University of
Toronto, (6)Gastroenterology and Hepatology, University of
California San Francisco, (7)University of North Carolina at
Chapel Hill, (8)Division of Gastroenterology and Hepatology,
Beth Israel Deaconess Medical Center, Harvard Medical
School, (9)Niddk, National Institutes of Health, (10)Division
of Gastroenterology, Hepatology and Nutrition, Virginia
Commonwealth University, (11)Hightide Therapeutics, (12)
Baylor University Medical Center, (13)Washington University
School of Medicine, (14)California Pacific Medical Center,
(15)Liver Center, Gastroenterology Division, Department
of Medicine, Massachusetts General Hospital, (16)Toronto
Centre for Liver Disease, Toronto General Hospital, University
Health Network, (17)Mayo Clinic Rochester, (18)Division of
Gastroenterology, University of Washington, (19)University
of Minnesota, (20)Queen’s Medical Centerr, (21)University of
Pittsburgh
Background: Loss of HBsAg with antiviral therapy is
associated with improved long-term outcomes but is
infrequently achieved Strategies to promote HBsAg loss with
available HBV therapies are highly desirable We evaluated
the safety and efficacy of finite therapy with tenofovir (TDF)
alone or in combination with peginterferon alfa-2b (PEGIFN)
followed by protocolized treatment withdrawal after 192
weeks of treatment in participants with HBeAg-positive or
-negative chronic hepatitis B Methods: A randomized (1:1)
trial of TDF (300 mg daily) for 192 weeks with or without PEGIFN
(180 μg weekly) for the first 24 weeks was followed by
a protocolized withdrawal of TDF at week 192 (in HBeAg
negative participants without baseline cirrhosis and HBV DNA
<1000 IU/mL) with the primary outcome being HBsAg loss at
week 240 Enrollment criteria included: (1) no previous antiviral
therapy for ≥24 weeks; (2) ALT levels above 1.5 times ULN; (3)
HBV DNA levels ≥1000 IU/mL; (4) compensated liver disease.
Participants were stratified by HBeAg status, genotype (A vs.
others) and cirrhosis (yes vs no) for randomization Results:
201 participants (65% male, 17% non-Asian, median age 41
years) were randomized to TDF with PEG-IFN (n=99) or TDF
alone (n=102) At baseline, 52% were HBeAg positive, 12%
had genotype A, 7% had cirrhosis, median (IQR) ALT 71 U/L
(49, 119), HBV DNA 6 5 log10 IU/mL (5 2, 8 1) and qHBsAg
3 7 (3 0, 4 3) log10 IU/mL The two groups (designated A and
B in preparation of unmasking results after trial ends) were
well balanced in regard to demographic features, ALT, HBV
DNA and HBsAg levels At end of treatment, HBV DNA was
<20 IU/mL in 90% and HBsAg was negative in 2 7% with
differences by treatment group (Table) Among HBeAgpositive
participants, 44% became HBeAg-negative At week
192, 111 participants stopped treatment, 105 of whom have
reached week 240 Rates of HBsAg loss at week 240 in both
participants with and without treatment withdrawal will be
available for presentation Conclusion: At end of treatment,
there were significant differences in HBV markers and ALT
between treatment groups; unmasked results from weeks
192 and 240 will be presented The impact of this treatment
strategy using a 24-week course of PEG-IFN at the start of
long-term nucleotide therapy, and the feasibility and results
following TDF withdrawal will help inform management of
patients with chronic hepatitis B until more effective antiviral
therapies are available.

Disclosures:
Norah Terrault – Gilead Sciences: Grant/Research Support; Roche-Genetech:
Grant/Research Support
Anna S Lok – Bristol Myers Squibb: Grant/Research Support; Gilead: Grant/
Research Support; TARGET: Grant/Research Support; Huahui: Consulting;
Eli Lilly: Consulting; Ambys: Consulting; Novo Nordisk: Advisory Committee or
Review Panel
David Kh Wong – Abbvie: Consulting; Merck: Speaking and Teaching
Mandana Khalili – Intercept Pharmaceuticals: Grant/Research Support; Gilead
Sciences Inc: Consulting; Gilead Sciences Inc: Grant/Research Support
Richard K Sterling – Abbott: Grant/Research Support; Roche: Grant/Research
Support; AbbVie: Grant/Research Support; Gilead: Grant/Research Support;
Pfizer: Advisory Committee or Review Panel; Askbio: Advisory Committee or
Review Panel
Mauricio Lisker-Melman – Gilead: Speaking and Teaching; Abbvie: Speaking
and Teaching; SimplySpeaking: Speaking and Teaching
Raymond T Chung – Roche: Grant/Research Support; Kaleido: Grant/
Research Support; Boehringer: Grant/Research Support; Synlogic: Grant/
Research Support; Gilead: Grant/Research Support; Alnylam: Advisory
Committee or Review Panel; Abbvie: Grant/Research Support; BMS: Grant/
Research Support; Merck: Grant/Research Support; Janssen: Grant/Research
Support
Keyur Patel – Gilead Sciences Canada Inc : Advisory Committee or Review
Panel; Gilead Sciences Canada Inc : Grant/Research Support; Intercept:
Advisory Committee or Review Panel; Allergan: Advisory Committee or Review
Panel
Lewis R Roberts – Ariad Pahrmaceuticals: Grant/Research Support; Bayer:
Advisory Committee or Review Panel; BTG International: Grant/Research
Support; Gilead: Advisory Committee or Review Panel; Glycotest: Grant/
Research Support; Grail: Advisory Committee or Review Panel; QED
Therapeutics: Advisory Committee or Review Panel; RedHill: Grant/Research
Support; TARGET PharmaSolutions: Grant/Research Support; TAVEC:
Advisory Committee or Review Panel; Wako Diagnostics: Grant/Research
Support; AstraZeneca: Consulting
Harry L A Janssen – Arbutus, Arena, Enyo, Gilead Sciences, GlaxoSmithKline,
Janssen, Medimmune, Merck, Roche, Vir Biotechnology Inc , Viroclinics:
Consulting; AbbVie, Arbutus, Bristol Myers Squibb, Gilead Sciences, Janssen,
Medimmune, Merck, Roche: Grant/Research Support
The following people have nothing to disclose: Daryl Lau, Marc G Ghany,
Robert P Perrillo, Charles Landis, Mohamed A Hassan
Disclosure information not available at the time of publication: Abdus Wahed,
Michael W Fried, Adrian M Di Bisceglie, Stewart Cooper, Christopher A Aoki,
Steve Belle.

StephenW

19
使用或隨機化192週的替諾福韋試驗
前24週沒有PEG干擾素
繼成人之後的協議提款
慢性乙型肝炎
諾拉·特拉特（Norah Terrault）1,2，安娜·S·洛克（Anna S.
Kh Wong5，Mandana Khalili6，Michael W Fried7，Daryl
Lau8，Marc G.Ghany9，Richard K.Sterling10，Adrian M Di
Bisceglie11，Robert P.Perrillo12，Mauricio Lisker-Melman13，
Stewart Cooper14，Raymond T.Chung15，Keyur Patel16，劉易斯
羅伯茨（R. Roberts）17，查爾斯·蘭迪斯（Charles Landis）18，穆罕默德·哈桑（Mohamed A.Hassan）19，
Christopher A.Aoki20，Steve Belle21和Harry L.A. Janssen16，
（1）大學消化道與肝病科
南加州大學，（2）胃腸道和肝病，大學
南加州大學（3）密歇根大學（4）學校
匹茲堡大學公共衛生學院，（5）
多倫多大學（6）腸胃病學和肝病學
加州舊金山（7）北卡羅來納大學
教堂山（8）胃腸病和肝病科，
哈佛醫學貝絲以色列女執事醫療中心
學校（9）國立衛生研究院（Niddk），國家衛生研究院（10）部門
弗吉尼亞胃腸病學，肝病學和營養學
英聯邦大學，（11）Hideide治療學，（12）
貝勒大學醫學中心，（13）華盛頓大學
（14）加利福尼亞太平洋醫學中心醫學院
（15）消化內科肝病中心
馬薩諸塞州總醫院醫學部（16）多倫多
大學多倫多總醫院肝病中心
衛生網絡，（17）羅切斯特市梅奧診所，（18）
華盛頓大學胃腸病學，（19）大學
明尼蘇達州立大學（20）女王醫療中心（21）大學
匹茲堡
背景：抗病毒治療導致HBsAg丟失是
與改善長期結果相關，但
很少實現促進HBsAg丟失的策略
我們非常希望有可用的HBV療法
替諾福韋（TDF）有限治療的安全性和有效性
單獨或與聚乙二醇干擾素α-2b（PEGIFN）組合使用
然後在192後退出方案治療
HBeAg陽性或
陰性慢性乙型肝炎方法：隨機（1：1）
有或沒有PEGIFN的TDF（每天300 mg）試驗192週
（每週180微克）在最初的24周中
協議的第192週撤回TDF（在HBeAg中
陰性參與者，無基線肝硬化和HBV DNA
<1000 IU / mL），主要結果是在
第240週的入學條件包括：（1）以前沒有抗病毒藥
治療≥24週； （2）ALT水平是ULN的1.5倍以上； （3）
HBV DNA水平≥1000IU / mL； （4）代償性肝病。
參與者按HBeAg狀態，基因型進行分層（A對
其他）和肝硬化（是或不是）以進行隨機分組結果：
201位參與者（65％的男性，17％的非亞裔，中位年齡41歲）
年）隨機分為PEG-IFN（n = 99）或TDF
單獨（n = 102）基線時，HBeAg陽性為52％，基線為12％
基因型為A，肝硬化為7％，中位數（IQR）ALT 71 U / L
（49，119），HBV DNA 6 5 log10 IU / mL（5 2，8 1）和qHBsAg
3 7（3 0，4 3）log10 IU / mL兩組（分別為A和
B為準備在試驗結束後揭露結果）
在人口統計學特徵，ALT，HBV方面保持平衡
DNA和HBsAg水平在治療結束時，HBV DNA為
<20 IU / mL佔90％，HBsAg陰性2 7％
各治療組之間HBe陽性的差異（表）
參加者，每周有44％成為HBeAg陰性
192，111位參與者停止了治療，其中105位已經接受治療
兩者均在第240周達到HBsAg丟失率
有戒斷治療的參與者將
結論：治療結束後，
HBV標誌物和ALT有顯著差異
治療組之間；數週未公開的結果
將介紹192和240
策略開始時使用24週療程的PEG-IFN
長期核苷酸療法及其可行性和結果
TDF撤出後將有助於告知管理
慢性乙型肝炎患者，直到更有效的抗病毒藥
有治療方法。