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

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

doi:10.1053/j.gastro.2015.09.043

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

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 ReiserHendrick 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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

260 Citations (Scopus)

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.

Original language	English
Pages (from-to)	134-144.e10
Journal	Gastroenterology
Volume	150
Issue number	1
DOIs	https://doi.org/10.1053/j.gastro.2015.09.043
Publication status	Published - 2016 Jan 1

Bibliographical note

Funding Information:
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 Information:
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.

Publisher Copyright:
© 2016 AGA Institute.

All Science Journal Classification (ASJC) codes

Hepatology
Gastroenterology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1053/j.gastro.2015.09.043

Cite this

Marcellin, P., Ahn, S. H., Ma, X., Caruntu, F. A., Tak, W. Y., Elkashab, M., Chuang, W. L., Lim, S. G., Tabak, F., Mehta, R., Petersen, J., Foster, G. R., Lou, L., Martins, E. B., Dinh, P., Lin, L., Corsa, A., Charuworn, P., Subramanian, G. M., ... Chan, H. L. Y. (2016). Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in Patients with Chronic Hepatitis B. Gastroenterology, 150(1), 134-144.e10. https://doi.org/10.1053/j.gastro.2015.09.043

@article{c2d28e149b0648e189b064a7bbe13757,

title = "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.",

author = "Patrick Marcellin and Ahn, {Sang Hoon} and Xiaoli Ma and Caruntu, {Florin A.} and Tak, {Won Young} and Magdy Elkashab and Chuang, {Wan Long} and Lim, {Seng Gee} and Fehmi Tabak and Rajiv Mehta and Joerg Petersen and Foster, {Graham R.} and Lillian Lou and Martins, {Eduardo B.} and Phillip Dinh and Lanjia Lin and Amoreena Corsa and Prista Charuworn and Subramanian, {G. Mani} and Hans Reiser and Reesink, {Hendrick W.} and Scott Fung and Strasser, {Simone I.} and Huy Trinh and Maria Buti and Gaeta, {Giovanni B.} and Hui, {Aric J.} and George Papatheodoridis and Robert Flisiak and Chan, {Henry L.Y.}",

note = "Funding Information: 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 Information: 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. Publisher Copyright: {\textcopyright} 2016 AGA Institute.",

year = "2016",

month = jan,

day = "1",

doi = "10.1053/j.gastro.2015.09.043",

language = "English",

volume = "150",

pages = "134--144.e10",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders Ltd",

number = "1",

}

Marcellin, P, Ahn, SH, Ma, X, Caruntu, FA, Tak, WY, Elkashab, M, Chuang, WL, Lim, SG, Tabak, F, Mehta, R, Petersen, J, Foster, GR, Lou, L, Martins, EB, Dinh, P, Lin, L, Corsa, A, Charuworn, P, Subramanian, GM, Reiser, H, Reesink, HW, Fung, S, Strasser, SI, Trinh, H, Buti, M, Gaeta, GB, Hui, AJ, Papatheodoridis, G, Flisiak, R & Chan, HLY 2016, 'Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in Patients with Chronic Hepatitis B', Gastroenterology, vol. 150, no. 1, pp. 134-144.e10. https://doi.org/10.1053/j.gastro.2015.09.043

TY - JOUR

T1 - Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in Patients with Chronic Hepatitis B

AU - Marcellin, Patrick

AU - Ahn, Sang Hoon

AU - Ma, Xiaoli

AU - Caruntu, Florin A.

AU - Tak, Won Young

AU - Elkashab, Magdy

AU - Chuang, Wan Long

AU - Lim, Seng Gee

AU - Tabak, Fehmi

AU - Mehta, Rajiv

AU - Petersen, Joerg

AU - Foster, Graham R.

AU - Lou, Lillian

AU - Martins, Eduardo B.

AU - Dinh, Phillip

AU - Lin, Lanjia

AU - Corsa, Amoreena

AU - Charuworn, Prista

AU - Subramanian, G. Mani

AU - Reiser, Hans

AU - Reesink, Hendrick W.

AU - Fung, Scott

AU - Strasser, Simone I.

AU - Trinh, Huy

AU - Buti, Maria

AU - Gaeta, Giovanni B.

AU - Hui, Aric J.

AU - Papatheodoridis, George

AU - Flisiak, Robert

AU - Chan, Henry L.Y.

N1 - Funding Information: 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 Information: 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. Publisher Copyright: © 2016 AGA Institute.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

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U2 - 10.1053/j.gastro.2015.09.043

DO - 10.1053/j.gastro.2015.09.043

M3 - Article

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AN - SCOPUS:84952700780

SN - 0016-5085

VL - 150

SP - 134-144.e10

JO - Gastroenterology

JF - Gastroenterology

IS - 1

ER -

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

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