Randomized, three‐arm study to optimize lamivudine efficacy in hepatitis B e antigen‐positive chronic hepatitis B patients

• DOI: 10.1111/jgh.12835
• Publication Date: 2014-10-29T02:10:09Z
• Authors: Xieer Liang; Jun Cheng; Yongtao Sun; Xinyue Chen; Tong Li; Hao Wang; Jianning Jiang; Xiaoping Chen; Hui Long; Hong Tang; Yanyan Yu; Jifang Sheng; Shijun Chen; Junqi Niu; Hong Ren; Junping Shi; Xiaoguang Dou; Mobin Wan; Jiaji Jiang; Qing Xie; Guangfeng Shi; Qin Ning; Chengwei Chen; Deming Tan; Hong Ma; Jian Sun; Jidong Jia; Hui Zhuang; Jinlin Hou
• Keywords: Adult; Male; 0301 basic medicine; Time Factors; Adolescent; Adenine; Organophosphonates; Middle Aged; Antiviral Agents; 3. Good health; Young Adult; 03 medical and health sciences; Hepatitis B, Chronic; Treatment Outcome; Lamivudine; Humans; Drug Therapy, Combination; Female; Hepatitis B e Antigens; Biomarkers; Aged

AbstractBackground and AimData 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).MethodsAdult patients without antiviral therapy within 6 months before screening with hepatitis B virus (HBV)‐DNA ≥ 105 copies/mL, alanine aminotransferase 1.3–10 times upper limit of normal and compensated hepatitis B e antigen (HBeAg)‐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/mL at week 24) from week 30 to week 104, whereas patients with early virological response (HBV‐DNA ≤ 1000 copies/mL at week 24) continued MONO until week 104. For all the patients receiving MONO, ADV would be added if virological breakthrough was confirmed.ResultsAt week 104, more patients in COMBO and OPTIMIZE groups achieved HBV‐DNA < 300 copies/mL (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/mL 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/mL 73.1% [38/52], HBeAg seroconversion 40.4% [21/52]). All regimens were well tolerated.ConclusionCombination therapy of lamivudine plus ADV exhibited effective viral suppression and relatively low resistance in HBeAg‐positive CHB patients. In lamivudine‐treated patients with suboptimal virological response at week 24, promptly adding on ADV is necessary to prevent resistance development.