TY - JOUR
TI - Predictors of response to tenofovir disoproxil fumarate plus
peginterferon alfa-2a combination therapy for chronic hepatitis B
AU - Marcellin, P.
AU - Ahn, S. H.
AU - Chuang, W. -L.
AU - Hui, A. J. and
AU - Tabak, F.
AU - Mehta, R.
AU - Petersen, J.
AU - Lee, C. -M.
AU - Ma, X. and
AU - Caruntu, F. A.
AU - Tak, W. Y.
AU - Elkhashab, M.
AU - Lin, L.
AU - Wu, G.
AU - and Martins, E. B.
AU - Charuworn, P.
AU - Yee, L. J.
AU - Lim, S. G. and
AU - Foster, G. R.
AU - Fung, S.
AU - Morano, L.
AU - Samuel, D.
AU - Agarwal, K.
AU - and Idilman, R.
AU - Strasser, S. I.
AU - Buti, M.
AU - Gaeta, G. B. and
AU - Papatheodoridis, G.
AU - Flisiak, R.
AU - Chan, H. L. Y.
JO - Alimentary Pharmacology & Therapeutics
PY - 2016
VL - 44
TODO - 9
SP - 957-966
PB - Wiley
SN - 0269-2813, 1365-2036
TODO - 10.1111/apt.13779
TODO - null
TODO - 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 mu
g/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 log(10) 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.
ER -