Phase IV randomized clinical study: Peginterferon alfa-2a with adefovir or entecavir pre-therapy for HBeAg-positive chronic hepatitis B

Chao Wei Hsu, Wei Wen Su, Chuan Mo Lee, Cheng Yuan Peng, Wan Long Chuang, Jia Horng Kao, Heng Cheng Chu, Yi Hsiang Huang, Rong Nan Chien, Yun Fan Liaw

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Abstract

Background: Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive. Methods: This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N = 280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks, combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46 weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post-treatment. Results: No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%; and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (-0.56 IU/mL, -0.60 IU/mL, and -0.41 IU/mL, respectively). However, hepatitis B virus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p = 0.0369) at week 88. Sub-analysis of results revealed an association between on-treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was comparable among treatment groups. Conclusion: Pre-therapy with ADV or ETV followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in Taiwanese patients with HBeAg-positive CHB. Clinical trial ID: NCT: 00922207.

Original languageEnglish
JournalJournal of the Formosan Medical Association
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Hepatitis B e Antigens
Chronic Hepatitis B
Placebos
Therapeutics
Hepatitis B Surface Antigens
Alanine Transaminase
entecavir
Clinical Studies
adefovir
peginterferon alfa-2a
Safety
Taiwan
Hepatitis B virus
Interferons
Clinical Trials

Keywords

  • Adefovir
  • Chronic hepatitis B
  • Entecavir
  • Hepatitis B e antigen
  • Peginterferon alfa-2a

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Phase IV randomized clinical study : Peginterferon alfa-2a with adefovir or entecavir pre-therapy for HBeAg-positive chronic hepatitis B. / Hsu, Chao Wei; Su, Wei Wen; Lee, Chuan Mo; Peng, Cheng Yuan; Chuang, Wan Long; Kao, Jia Horng; Chu, Heng Cheng; Huang, Yi Hsiang; Chien, Rong Nan; Liaw, Yun Fan.

In: Journal of the Formosan Medical Association, 01.01.2018.

Research output: Contribution to journalArticle

Hsu, Chao Wei ; Su, Wei Wen ; Lee, Chuan Mo ; Peng, Cheng Yuan ; Chuang, Wan Long ; Kao, Jia Horng ; Chu, Heng Cheng ; Huang, Yi Hsiang ; Chien, Rong Nan ; Liaw, Yun Fan. / Phase IV randomized clinical study : Peginterferon alfa-2a with adefovir or entecavir pre-therapy for HBeAg-positive chronic hepatitis B. In: Journal of the Formosan Medical Association. 2018.
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title = "Phase IV randomized clinical study: Peginterferon alfa-2a with adefovir or entecavir pre-therapy for HBeAg-positive chronic hepatitis B",
abstract = "Background: Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive. Methods: This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N = 280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks, combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46 weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post-treatment. Results: No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3{\%}; PEG-IFN alfa-2a+ETV, 29.5{\%}; and PEG-IFN alfa-2a+ADV, 27.4{\%}), HBeAg loss (37.4{\%}, 32.2{\%}, and 28.6{\%}, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (-0.56 IU/mL, -0.60 IU/mL, and -0.41 IU/mL, respectively). However, hepatitis B virus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p = 0.0369) at week 88. Sub-analysis of results revealed an association between on-treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was comparable among treatment groups. Conclusion: Pre-therapy with ADV or ETV followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in Taiwanese patients with HBeAg-positive CHB. Clinical trial ID: NCT: 00922207.",
keywords = "Adefovir, Chronic hepatitis B, Entecavir, Hepatitis B e antigen, Peginterferon alfa-2a",
author = "Hsu, {Chao Wei} and Su, {Wei Wen} and Lee, {Chuan Mo} and Peng, {Cheng Yuan} and Chuang, {Wan Long} and Kao, {Jia Horng} and Chu, {Heng Cheng} and Huang, {Yi Hsiang} and Chien, {Rong Nan} and Liaw, {Yun Fan}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.jfma.2017.12.007",
language = "English",
journal = "Journal of the Formosan Medical Association",
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T1 - Phase IV randomized clinical study

T2 - Peginterferon alfa-2a with adefovir or entecavir pre-therapy for HBeAg-positive chronic hepatitis B

AU - Hsu, Chao Wei

AU - Su, Wei Wen

AU - Lee, Chuan Mo

AU - Peng, Cheng Yuan

AU - Chuang, Wan Long

AU - Kao, Jia Horng

AU - Chu, Heng Cheng

AU - Huang, Yi Hsiang

AU - Chien, Rong Nan

AU - Liaw, Yun Fan

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive. Methods: This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N = 280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks, combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46 weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post-treatment. Results: No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%; and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (-0.56 IU/mL, -0.60 IU/mL, and -0.41 IU/mL, respectively). However, hepatitis B virus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p = 0.0369) at week 88. Sub-analysis of results revealed an association between on-treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was comparable among treatment groups. Conclusion: Pre-therapy with ADV or ETV followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in Taiwanese patients with HBeAg-positive CHB. Clinical trial ID: NCT: 00922207.

AB - Background: Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive. Methods: This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N = 280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks, combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46 weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post-treatment. Results: No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%; and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (-0.56 IU/mL, -0.60 IU/mL, and -0.41 IU/mL, respectively). However, hepatitis B virus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p = 0.0369) at week 88. Sub-analysis of results revealed an association between on-treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was comparable among treatment groups. Conclusion: Pre-therapy with ADV or ETV followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in Taiwanese patients with HBeAg-positive CHB. Clinical trial ID: NCT: 00922207.

KW - Adefovir

KW - Chronic hepatitis B

KW - Entecavir

KW - Hepatitis B e antigen

KW - Peginterferon alfa-2a

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DO - 10.1016/j.jfma.2017.12.007

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