Phase IV randomized clinical study: Peginterferon alfa-2a with adefovir or entecavir pre-therapy for HBeAg-positive chronic hepatitis B
Autor: | Chao Wei Hsu, Chuan Mo Lee, Yun Fan Liaw, Heng Cheng Chu, Rong-Nan Chien, Wan-Long Chuang, Jia-Horng Kao, Yi Hsiang Huang, Cheng Yuan Peng, Wei Wen Su |
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Rok vydání: | 2017 |
Předmět: |
Adult
Male medicine.medical_specialty HBsAg Hepatitis B virus Guanine Organophosphonates Taiwan Placebo Gastroenterology Antiviral Agents Drug Administration Schedule Polyethylene Glycols 03 medical and health sciences 0302 clinical medicine Hepatitis B Chronic Chronic hepatitis Double-Blind Method Internal medicine medicine Adefovir Humans Hepatitis B e Antigens lcsh:R5-920 Hepatitis B Surface Antigens business.industry Adenine virus diseases Interferon-alpha Alanine Transaminase General Medicine Entecavir Middle Aged digestive system diseases Recombinant Proteins Clinical trial HBeAg 030220 oncology & carcinogenesis DNA Viral 030211 gastroenterology & hepatology Drug Therapy Combination Female lcsh:Medicine (General) business medicine.drug Peginterferon alfa-2a |
Zdroj: | Journal of the Formosan Medical Association, Vol 117, Iss 7, Pp 588-597 (2018) |
ISSN: | 0929-6646 |
Popis: | 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: Chronic hepatitis B, Hepatitis B e antigen, Peginterferon alfa-2a, Adefovir, Entecavir |
Databáze: | OpenAIRE |
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