104-week efficacy and safety of telbivudine based optimization strategy in chronic hepatitis B patients: A randomized, controlled study
Jian Sun 1,
Qing Xie 2,
Deming Tan 3,
Qin Ning 4,
Junqi Niu 5,
Xuefan Bai 6,
Rong Fan 1,
Shijun Chen 7,
Jun Cheng 8,
Yanyan Yu 9,
Hao Wang 10,
Min Xu 11,
Guangfeng Shi 12,
Mobin Wan 13,
Xinyue Chen 14,
Hong Tang 15,
Jifang Sheng 16,
Xiaoguang Dou 17,
Junping Shi 18,
Hong Ren 19,
Maorong Wang 20,
Hongfei Zhang 21,
Zhiliang Gao 22,
Chengwei Chen 23,
Hong Ma 24,
Jidong Jia 24,
Jinlin Hou 1,*
Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou
2
Department of Infectious Diseases, Ruijin Hospital, Shanghai
3
Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha
4
Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
5
Hepatology Unit, No. 1 Hospital affiliated to Jilin University, Changchun
6
Department of Infectious Diseases, Tangdu Hospital, Xi'an
7
Ji'nan Infectious Diseases Hospital, Ji'nan
8
Beijing Ditan Hospital, Beijing
9
Department of Infectious Diseases, First Hospital of Peking University, Beijing
10
Hepatology Unit, Peking University People's Hospital, Beijing
11
8th People's Hospital, Guangzhou
12
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai
13
Department of Infectious Diseases, Changhai Hospital, Shanghai
14
Beijing Youan Hospital, Beijing
15
Department of Infectious Diseases, West China Hospital, Chengdu
16
Department of Infectious Diseases, Zhejiang University 1st Affiliated Hospital, Hangzhou
17
Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang
18
6th People's Hospital, Hangzhou
19
Department of Infectious Diseases, The second Affiliated Hospital, Chongqing Medical University, Chongqing
20
Department of Infectious Diseases, 81st PLA Hospital, Nanjing
21
302nd PLA Hospital, Beijing
22
Department of Infectious Diseases, Sun Yat-Sen University 3rd Affiliated Hospital, Guangzhou
23
Department of Infectious Diseases, 85th PLA Hospital, Shanghai
24
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
*Correspondence: Jinlin Hou, Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China Tel: 00862061641941 Fax: 00862087719653 Email: [email protected]
Abstract
Optimization strategy based on ROADMAP concept is supposed to improve the clinical outcomes of patients with suboptimal antiviral response. The aim of this study is to prove the concept with a multicenter, open-label, randomized, controlled study. Six hundred and six Hepatitis B e antigen (HBeAg) -positive, nucleos(t)ide -naive chronic hepatitis B patients were randomized to OPTIMIZE or MONO group. Patients in OPTIMIZE group were treated with telbivudine for 24 weeks, after which those suboptimal responders with HBV DNA ≥ 300 copies/mL at week 24 received telbivudine plus adefovir until week 104, while the early virological responders continued telbivudine monotherapy. Patients in MONO group received telbivudine monotherapy. All patients with telbivudine monotherapy were added on adefovir if viral breakthrough developed. Sixty eight percent (204/300) patients in OPTIMIZE group were added on adefovir due to suboptimal response. At week 104, compared to MONO group, more patients in OPTIMIZE group achieved HBV DNA < 300 copies/ml (76.7% vs. 61.2%, p<0.001) with less genotypic resistance (2.7% vs. 25.8%, p<0.001). The rates of HBeAg seroconversion and ALT normalization were comparable between two groups (23.7% vs. 22.1%; 80.7% vs. 79.2%). For week 24 suboptimal responders, telbivudine plus adefovir showed additive antiviral potency with 71.1% achieving virological response at week 104 and only 0.5% developing genotypic resistance, compared with 46.6% who achieved virological response and 37.8% who developed genotypic resistance with telbivudine monotherapy. Both treatment regimens were well tolerated with observed persistent increase of glomerular filtration rate. Conclusion: For suboptimal virological responders to telbivudine at week 24, adjusting treatment strategy is recommended. Adding on adefovir can benefit these patients with additive antiviral potency and low resistance without increased side effect. (Hepatology 2013;)