Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B.

Abstract

BACKGROUND & AIMS:

Patients chronically infected with the hepatitis B virus rarely achieve loss of serum hepatitis B surface antigen (HBsAg) with the standard of care. We evaluated HBsAg loss in patients receiving the combination of tenofovir disoproxil fumarate (TDF) and peginterferon α-2a (peginterferon) for a finite duration in a randomized trial.

METHODS:

In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus peginterferon for 48 weeks (group A), TDF plus peginterferon for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or peginterferon for 48 weeks (group D). The primary end point was the proportion of patients with serum HBsAg loss at week 72.

RESULTS:

At week seventy-two, 9.1% of subjects in group A had HBsAg loss compared with 2.8% of subjects in group B, none of the subjects in group C, and 2.8% of subjects in group D. A significantly higher proportion of subjects in group A had HBsAg loss than in group C (P < .001) or group D (P = .003). However, the proportions of subjects with HBsAg loss did not differ significantly between group B and group C (P = .466) or group D (P = .883). HBsAg loss in group A occurred in hepatitis B e antigen-positive and hepatitis B e antigen-negative patients with all major viral genotypes. The incidence of common adverse events (including headache, alopecia, and pyrexia) and treatment discontinuation due to adverse events was similar among groups.

CONCLUSIONS:

A significantly greater proportion of patients receiving TDF plus peginterferon for 48 weeks had HBsAg loss than those receiving TDF or peginterferon alone. ClinicalTrials.gov ID NCT01277601.

• Authors: Patrick Marcellin, Sang Hoon Ahn, Xiaoli Ma, Florin A Caruntu, Won Young Tak, Magdy Elkashab, Wan-Long Chuang, Seng-Gee Lim, Fehmi Tabak, Rajiv Mehta, Joerg Petersen, Graham R Foster, Lillian Lou, Eduardo B Martins, Phillip Dinh, Lanjia Lin, Amoreena Corsa, Prista Charuworn, G Mani Subramanian, Hans Reiser, Hendrick W Reesink, Scott Fung, Simone I Strasser, Huy Trinh, Maria Buti, Giovanni B Gaeta, Aric J Hui, George Papatheodoridis, Robert Flisiak, Henry L Y Chan, Study 149 Investigators
• Journal: Gastroenterology (Gastroenterology) Vol. 150 Issue 1 Pg. 134-144.e10 (Jan 2016) ISSN: 1528-0012 [Electronic] United States
• PMID: 26453773 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Hepatitis B Surface Antigens
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Tenofovir
• peginterferon alfa-2a

Topics

• Administration, Oral
• Adolescent
• Adult
• Aged
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Hepatitis B Surface Antigens (blood, drug effects)
• Hepatitis B, Chronic (blood, diagnosis, drug therapy, mortality)
• Humans
• Injections, Subcutaneous
• Interferon-alpha (therapeutic use)
• Internationality
• Kaplan-Meier Estimate
• Male
• Markov Chains
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Prognosis
• Recombinant Proteins (therapeutic use)
• Risk Assessment
• Severity of Illness Index
• Survival Rate
• Tenofovir (therapeutic use)
• Treatment Outcome
• Viral Load (drug effects)
• Young Adult