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

doi:10.1053/j.gastro.2015.09.043

Gastroenterology

Volume 150, Issue 1, January 2016, Pages 134-144.e10

https://doi.org/10.1053/j.gastro.2015.09.043 Get rights and content

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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.

Keywords

HBV

HBeAg Seroconversion

Virologic Response

Clinical Trial

Abbreviations used in this paper

ALT

alanine aminotransferase

CHB

chronic hepatitis B

HBeAg

hepatitis B e antigen

HBsAg

hepatitis B surface antigen

HBV

hepatitis B virus

peginterferon

pegylated interferon-α

S/CO

sample/cutoff relative light units of quantitative HBsAg

TDF

tenofovir disoproxil fumarate

Cited by (0)

: Conflicts of interest These authors disclose the following: Patrick Marcellin: Speaker and investigator for Bristol-Myers Squibb, Boehringer-Ingelheim, Gilead Sciences, Janssen, Merck, Roche, and Tibotec. Sang Hoon Ahn: Advisor and lecturer for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, MSD, Novartis, Roche. Unrestricted research grants from Bristol-Myers Squibb, Gilead Sciences, and Roche. Florin A Caruntu: Advisor and speaker for AbbVie, Bristol-Myers Squibb, Gilead Sciences, GSK, Janssen, MSD, and Roche. Research grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Roche. Magdy Elkashab: CME speaker fees and Advisory Board consultation fees from Gilead Sciences. Wan-Long Chuang: Member of advisory board: AbbVie, Boehringer Ingelheim, Gilead Sciences, Novartis, Roche; Speaker: Bristol-Myer Squibb, Gilead Sciences, MSD, and Roche. Seng Gee Lim: Advisory Board member: AbbVie, Boehingher Ingelheim, Bristol-Myer Squibb, Gilead Sciences, MSD, Novartis, Pfizer, Vertex, Tobira; Speakers Bureau: Bristol-Myers Squibb, GSK, Novartis, Roche. Educational/research funding: Bristol-Myers Squibb, Gilead Sciences, MSD, Novartis. Fehmi Tabak: Local advisor for AbbVie, Bristol-Myers Squibb, Gilead Sciences, GSK, and speaker for AbbVie, Bristol-Myers Squibb, Gilead Sciences, GSK, and Janssen. Joerg Petersen: Grant/Research Support from Bristol-Myers Squibb, Novartis, Roche; research support from: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Janssen, Merck, MSD, Roche, Siemens, Vertex; Consultant/Advisor for Abbott, AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, GSK, Kedrion, Janssen, Merck, MSD, Novartis, Roche; Sponsored lectures: Abbott, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Kedrion, Janssen, Merck, MSD, Novartis, Roche. Graham R Foster: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Gilead Sciences, Roche, Merck, Novartis, Tekmira. Lilian Lou: Stockholder of Gilead Sciences, Inc and former employee. Eduardo B Martins: Employee and stockholder of Gilead Sciences, Inc Philip Dinh: Employee and stockholder of Gilead Sciences, Inc Lanjia Lin: Employee and stockholder of Gilead Sciences, Inc Amy Corsa: Employee and stock holder of Gilead Sciences, Inc Prista Charuworn: Employee and stockholder of Gilead Sciences, Inc G. Mani Subramanian: Employee and stockholder of Gilead Sciences, Inc Hans Reiser: Employee and stock holder of Gilead Sciences, Inc Hendrick W Reesink: Consulting for AbbVie, Alnylam, Astex, Bristol-Myers Squibb, Gilead Sciences, GSK, Janssen-Cilag, Korean Green Cross, MSD, PRA-International, Regulus, Replicor, Roche, R-Pharm, Santaris; Research support from: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, MSD, PRA-International, Regulus, Replicor, Roche, Santaris. Scott Fung: Research grants, speaker and advisor for: AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Roche; Research grant from Boehringer Ingelheim. Consultant: GSK. Simone I Strasser: Speaker and advisory board member for AbbVie, Bayer, Bristol-Myers Squibb, Gilead Sciences, Janssen, MSD/Merck, Norgine, Roche. Huy Trinh: Speaker, advisory board member, and research grants for/from Bristol-Myers Squibb and Gilead Sciences. Stockholder for Gilead Sciences Inc Maria Buti: Gilead Sciences, MSD and Novartis. Giovanni Gaeta: Speaker or advisor for: AbbVie, Bristol Myers Squibb, Gilead Sciences, Merck, Roche. George Papatheodoridis: Advisor/lecturer for Bristol-Myers Squibb, Gilead Sciences, Novartis and Roche; research grants from Bristol-Myers Squibb, Gilead Sciences and Roche. Robert Flisiak: Research grants from Bristol-Myers Squibb, Gilead Sciences, Janssen, MSD, Novartis, Roche. Advisory board member for AbbVie, Bristol-Myer Squibb, Boehringer-Ingelheim, Gilead Sciences, Janssen, MSD, Novartis, Roche. Speaker for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, MSD, Roche. Henry L. Y. Chan: Advisor and speaker for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Roche, MSD and Novartis; speaker for GSK, Echosens; unrestricted grant for HBV research from Roche. The remaining authors disclose no conflicts.

: Funding This study was supported by Gilead Sciences. The study was designed and conducted according to the protocol by the sponsor (Gilead Sciences) in collaboration with the principal investigators. The sponsor collected the data, monitored the study conduct, and performed the statistical analysis. All authors had access to the data and assume responsibility for the integrity and completeness of the reported data. All authors made substantial contributions to the conception or design of the study, acquisition, analysis, or interpretation of the data and were involved in the drafting of the manuscript. Phillip Dinh and Lanjia Lin provided statistical analysis. The final decision to submit the manuscript for publication was the responsibility of Patrick Marcellin and Henry L. Y. Chan. Writing support was provided by Dr Liesje Quine, Elements Communications Ltd, Westerham, Kent and funded by Gilead Sciences.

: Author names in bold designate shared co-first authorship.

^§: Authors share co-senior authorship.