Phase IV randomized clinical study: Peginterferon alfa-2a with adefovir or entecavir pre-therapy for HBeAg-positive chronic hepatitis B
Journal
Journal of the Formosan Medical Association
Journal Volume
117
Journal Issue
7
Pages
588-597
Date Issued
2018
Author(s)
Hsu C.-W.
Su W.-W.
Lee C.-M.
Peng C.-Y.
Chuang W.-L.
Chu H.-C.
Huang Y.-H.
Chien R.-N.
Liaw Y.-F.
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. ? 2018
Subjects
Adefovir; Chronic hepatitis B; Entecavir; Hepatitis B e antigen; Peginterferon alfa-2a
SDGs
Other Subjects
adefovir; adefovir dipivoxil; alanine aminotransferase; antivirus agent; entecavir; gamma interferon; hepatitis B(e) antigen; lamivudine; peginterferon alpha2a; placebo; telbivudine; tenofovir; virus DNA; adefovir; adenine; alanine aminotransferase; alpha interferon; antivirus agent; entecavir; guanine; hepatitis B surface antigen; hepatitis B(e) antigen; macrogol; peginterferon alpha2a; phosphonic acid derivative; recombinant protein; virus DNA; adult; alanine aminotransferase blood level; alopecia; antiviral therapy; Article; cellulitis; chronic hepatitis B; controlled study; decreased appetite; diarrhea; dizziness; double blind procedure; drug efficacy; drug safety; fatigue; female; fever; gingiva bleeding; headache; Hepatitis B virus; human; hyperthyroidism; insomnia; liver failure; major clinical study; male; monotherapy; multicenter study; myalgia; nausea; neutropenia; phase 4 clinical trial; pruritus; randomized controlled trial; rash; rhinopharyngitis; seroconversion; side effect; Taiwanese; unspecified side effect; upper respiratory tract infection; analogs and derivatives; blood; chronic hepatitis B; clinical trial; combination drug therapy; drug administration; genetics; middle aged; Taiwan; Adenine; Adult; Alanine Transaminase; Antiviral Agents; DNA, Viral; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Guanine; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Interferon-alpha; Male; Middle Aged; Organophosphonates; Polyethylene Glycols; Recombinant Proteins; Taiwan
Publisher
Elsevier B.V.
Type
journal article