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Randomized, three‐arm study to optimize lamivudine efficacy in hepatitis B e antigen‐positive chronic hepatitis B patients
Author(s) -
Liang Xieer,
Cheng Jun,
Sun Yongtao,
Chen Xinyue,
Li Tong,
Wang Hao,
Jiang Jianning,
Chen Xiaoping,
Long Hui,
Tang Hong,
Yu Yanyan,
Sheng Jifang,
Chen Shijun,
Niu Junqi,
Ren Hong,
Shi Junping,
Dou Xiaoguang,
Wan Mobin,
Jiang Jiaji,
Xie Qing,
Shi Guangfeng,
Ning Qin,
Chen Chengwei,
Tan Deming,
Ma Hong,
Sun Jian,
Jia Jidong,
Zhuang Hui,
Hou Jinlin
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12835
Subject(s) - lamivudine , adefovir , medicine , hepatitis b virus , hepatitis b , gastroenterology , virology , combination therapy , chronic hepatitis , virus
Background and Aim Data about the efficacy of de novo combination therapies, or optimization strategy by adding the other drug based on the virological response at week 24 of low genetic barrier antiviral agents is still limited. This study aimed to compare the efficacy at week 104 of lamivudine monotherapy ( MONO ), lamivudine plus adefovir dipivoxil ( ADV ) combination therapy ( COMBO ), and lamivudine optimization strategy ( OPTIMIZE ). Methods Adult patients without antiviral therapy within 6 months before screening with hepatitis B virus ( HBV )‐ DNA ≥ 10 5 copies/m L , alanine aminotransferase 1.3–10 times upper limit of normal and compensated hepatitis B e antigen ( HB e A g)‐positive chronic hepatitis B ( CHB ) were randomized into three groups with 1:1:1 ratio. Patients in OPTIMIZE group started with lamivudine 100 mg q.d., and ADV 10 mg q.d. was added to suboptimal responders ( HBV ‐ DNA > 1000 copies/m L at week 24) from week 30 to week 104, whereas patients with early virological response ( HBV ‐ DNA ≤ 1000 copies/m L at week 24) continued MONO until week 104. For all the patients receiving MONO , ADV would be added if virological breakthrough was confirmed. Results At week 104, more patients in COMBO and OPTIMIZE groups achieved HBV ‐ DNA < 300 copies/m L (53.3% [64/120] and 48.3% [58/120]), with less lamivudine resistance (0.8% and 6.7%) compared with MONO group ( HBV ‐ DNA < 300 copies/m L 34.8% [41/118], lamivudine resistance 58.5%). Patients under MONO with early virological response showed superior efficacy at week 104 ( HBV ‐ DNA < 300 copies/m L 73.1% [38/52], HB e A g seroconversion 40.4% [21/52]). All regimens were well tolerated. Conclusion Combination therapy of lamivudine plus ADV exhibited effective viral suppression and relatively low resistance in HB e A g‐positive CHB patients. In lamivudine‐treated patients with suboptimal virological response at week 24, promptly adding on ADV is necessary to prevent resistance development.