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Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa-2a combination therapy for chronic hepatitis B
Journal article   Open access   Peer reviewed

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, …
Alimentary pharmacology & therapeutics, v 44(9), pp 957-966
Nov 2016
PMID: 27629859
url
https://doi.org/10.1111/apt.13779View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Administration, Oral Adult Antiviral Agents - administration & dosage DNA, Viral - blood Drug Therapy, Combination Female Hepatitis B Surface Antigens - blood Hepatitis B virus - drug effects Hepatitis B virus - genetics Hepatitis B, Chronic - diagnosis Hepatitis B, Chronic - drug therapy Humans Injections, Subcutaneous Interferon-alpha - administration & dosage Male Middle Aged Polyethylene Glycols - administration & dosage Predictive Value of Tests Recombinant Proteins - administration & dosage Tenofovir - administration & dosage Treatment Outcome
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. 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. 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. 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 log 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. 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.

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Industry collaboration
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Web of Science research areas
Gastroenterology & Hepatology
Pharmacology & Pharmacy
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