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

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.

• Authors: 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 Fung, L Morano, D Samuel, K Agarwal, R Idilman, S I Strasser, M Buti, G B Gaeta, G Papatheodoridis, R Flisiak, H L Y Chan
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 44 Issue 9 Pg. 957-966 (11 2016) ISSN: 1365-2036 [Electronic] England
• PMID: 27629859 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B Surface Antigens
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Tenofovir
• peginterferon alfa-2a

Topics

• Administration, Oral
• Adult
• Antiviral Agents (administration & dosage)
• DNA, Viral (blood)
• Drug Therapy, Combination
• Female
• Hepatitis B Surface Antigens (blood)
• Hepatitis B virus (drug effects, genetics)
• Hepatitis B, Chronic (diagnosis, 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