Premium
Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa‐2a combination therapy for chronic hepatitis B
Author(s) -
Marcellin P.,
Ahn S. H.,
Chuang W.L.,
Hui A. J.,
Tabak F.,
Mehta R.,
Petersen J.,
Lee C.M.,
Ma X.,
Caruntu F. A.,
Tak W. Y.,
Elkhashab M.,
Lin L.,
Wu G.,
Martins E. B,
Charuworn P.,
Yee L. J.,
Lim S. G.,
Foster G. R.,
Fung S.,
Morano L.,
Samuel D.,
Agarwal K.,
Idilman R.,
Strasser S. I.,
Buti M.,
Gaeta G. B.,
Papatheodoridis G.,
Flisiak R.,
Chan H. L. Y.
Publication year - 2016
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.13779
Subject(s) - hbsag , medicine , tenofovir , gastroenterology , pegylated interferon , hepatitis b , combination therapy , hepatitis b virus , chronic hepatitis , immunology , virus , human immunodeficiency virus (hiv) , ribavirin
Summary 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 ( HB sAg) loss than either monotherapy. Aim To identify baseline and on‐treatment factors associated with HB sAg loss at Week 72 and provide a model for predicting HB sAg 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 HB sAg loss at Week 72. Results Rates of HB sAg 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. HB sAg decline at Week 12 or 24 of treatment was associated with HB sAg loss at Week 72 ( P < 0.001). HB sAg 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 HB sAg loss at Week 72. Conclusions HB sAg 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 HB sAg loss at Week 72.