Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa-2a combination therapy for chronic hepatitis B

P. Marcellin, S. H. Ahn, W. L. Chuang, A. J. Hui, F. Tabak, R. Mehta, J. Petersen, C. M. Lee, X. Ma, F. A. Caruntu, W. Y. Tak, M. Elkhashab, L. Lin, G. Wu, E. B. Martins, P. Charuworn, L. J. Yee, S. G. Lim, G. R. Foster, S. FungL. Morano, D. Samuel, K. Agarwal, R. Idilman, S. I. Strasser, M. Buti, G. B. Gaeta, G. Papatheodoridis, R. Flisiak, H. L.Y. Chan

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Background: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. Aim: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. Methods: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. Results: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72. Conclusions: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.

Original languageEnglish
Pages (from-to)957-966
Number of pages10
JournalAlimentary Pharmacology and Therapeutics
Volume44
Issue number9
DOIs
Publication statusPublished - 2016 Nov 1

Bibliographical note

Funding Information:
Declaration of personal interests: Patrick Marcellin: Speaker and investigator for Bristol-Myers Squibb, Boehinger Ingelheim, Gilead Sciences, Janssen, Merck, Roche and Tibotec. Sang Hoon Ahn: Advisor and lecturer for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Roche, MSD. Unrestricted grant from Bristol-Myers Squibb, Gilead Sciences, Roche for investigator initiated trials. Wan-Long Chuang: Advisory board member for AbbVie, Boehringer Ingelheim, Gilead Sciences, Novartis, Roche. Speaker for Bristol-Myers Squibb, Gilead Sciences, MSD and Roche. Aric Josun Hui, Chuan-Mo Lee, Xiaoli Ma, Won Young Tak, Luis Morano, Ramazan Idilman: Nothing to disclose. Fehmi Tabak: Local Advisor for AbbVie, Bristol-Myers Squibb, Gilead Sciences, GSK. Speaker for AbbVie, Bristol-Myers Squibb, Gilead Sciences, GSK, Janssen. Rajiv Mehta: Nothing to disclose. Joerg Petersen: Grant/research support from Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Janssen, Merck, MSD, Roche, Siemens, Vertex. Consultant/Advisor for Abbott, AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, GSK, Kadrion, Janssen, Merck, MSD, Novartis, Roche. Sponsored lectures for Abbott, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Kadrion, Janssen, Merck, MSD, Novartis, Roche. Florin Alexandru Caruntu: Advisor and speaker for AbbVie, Bristol-Myers Squibb, Gilead Sciences, GSK, Janssen, MSD, Roche. Research grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Roche. Magdy Elkhashab: CME speaker fees and Advisory Board consultation fees from Gilead Sciences. Lanjia Lin, George Wu, Leland Yee: Employee and stockholder of Gilead Sciences. Eduardo B Martins, Prista Charuworn: Former employee of Gilead Sciences. Seng Gee Lim: Advisory Board member for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, MSD, Novartis, Pfizer, Vertex, Tobira. Speakers bureau for Bristol-Myers Squibb, GSK, Novartis. Graham R Foster: Speaker and consultant for AbbVie, Boehringer, Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Roche, Merck, Novartis, Tekmira. Scott Fung: Research grants, speaker and Advisor for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Roche. Consultant for GSK. Didier Samuel: Receipt of honoraria fees: AbbVie, Astellas, Bristol-Myers Squibb, Biotest, Gilead Sciences, LFB, Merck Sharp & Dohme, Novartis. Kosh Agarwal: Honoraria for speaking at education events or consulting from: AbbVie, Astellas, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck and Novartis and research grants from Bristol-Myers Squibb, Gilead Sciences and Roche. Simone I Strasser: Speaker and advisory board member for AbbVie, Bayer, Bristol-Myers Squibb, Gilead Sciences, Janssen, MSD/Merck, Norgine, Roche. Maria Buti: Speaker and advisory board member for Gilead Sciences, MSD and Novartis. Giovanni B Gaeta: Speaker or Advisor for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Merck, Roche. George Papatheodoridis: Advisor/lecturer for Bristol-Myers Squibb, Gilead Sciences, Novartis, Roche. Research grants from Bristol-Myers Squibb, Gilead Sciences, Novartis, Roche. Robert Flisiak: Research grants from Bristol-Myers Squibb, Gilead Sciences, Janssen, MSD, Novartis, Roche. Advisory board member for AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Janssen, MSD, Novartis, Roche. Speaker for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, MSD, Roche. Henry LY Chan: Advisor and speaker for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Roche, MSD, Novartis. Speaker for GSK, Echosens. Unrestricted grant for HBV research from Roche. Declaration of funding interests: This study was funded in full by Gilead Sciences, Inc. Medical writing support was provided by Liesje Quine, Ph.D. (Elements Communications Ltd, Westerham, UK) funded by Gilead Sciences, Inc.

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa-2a combination therapy for chronic hepatitis B'. Together they form a unique fingerprint.

Cite this