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

30 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

Publisher Copyright:
© 2016 John Wiley & Sons Ltd

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