Jun Cheng1, Yuming Wang2, Jinlin Hou3, Duande Luo4, Qing Xie5, Qin Ning6, Hong Ren7, Huiguo Ding8, Jifang Sheng9, Lai Wei10, Shijun Chen11, Xiaoling Fan12, Wenxiang Huang13, Chen Pan14, Zhiliang Gao15, Jiming Zhang16, Boping Zhou17, Guofeng Chen18, Mobin Wan19, Hong Tang20, Guiqiang Wang21, Yuxiu Yang22, Rosmawati Mohamed23, Richard Guan24, Tzong-Hsi Lee25, Wen-Hsiung Chang26, Huang Zhenfei27, Zhang Ye27, Daozhen Xu28. 1. Beijing Ditan Hospital, Capital Medical University, No. 8, East Jingshun Street, Beijing 100015, China. Electronic address: jun.cheng.ditan@gmail.com. 2. Southwest Hospital Affiliated Third Military Medical University, No. 29, Gao Tan Yan Zhengjie, Shapingba, Chongqing 400038, China. 3. Guangzhou Nanfang Hospital, No. 1838, N. Guangzhou Avenue, Guangzhou 510515, China. 4. Xiehe Hospital Affiliated Tongji Medical College of Huazhong University of Science & Technology, No. 1277, Jiefang Avenue, Wuhan 430022, China. 5. Shanghai Ruijin Hospital Affiliated Shanghai Jiao Tong University, No. 197, Ruijiner Rd., Shanghai 200025, China. 6. Tongji Hospital Affiliated Tongji Medical College of Huazhong University of Science & Technology, No. 1095, Jiefang Avenue, Wuhan 430030, China. 7. The Second Affiliated Hospital, Chongqing Medical University, No. 76, Linjiang Rd., Chongqing 400010, China. 8. Beijing You'an Hospital, Capital Medical University, No. 8, You An Men Wai Street, Fengtai District, Beijing 100069, China. 9. The First Affiliated Hospital of Zhejiang University Medical College, No. 79, Qingchun Rd., Hangzhou 310003, China. 10. Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. 11. Jinan Infectious Disease Hospital, No. 173, Jingshi Rd., Jinan 250021, China. 12. Beijing Ditan Hospital, Capital Medical University, No. 8, East Jingshun Street, Beijing 100015, China. 13. No. 1 Hospital of Chongqing Medical University, No. 1, Youyi Rd., Chongqing 400016, China. 14. Fuzhou Infectious Disease Hospital, No. 312, Xihong Rd., Gulou District, Fuzhou 350025, China. 15. The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Rd., Guangzhou 510630, China. 16. Huashan Hospital, Fudan University, No. 12, Middle Wurumuqi Rd., Shanghai 200040, China. 17. Shenzhen Donghu Hospital, No. 2019, Buxin Rd., Shenzhen 518020, China. 18. Beijing 302 Hospital, No. 100, Xi Si Huan Zhong Lu, Beijing 100039, China. 19. Shanghai Changhai Hospital, No. 174, Changhai Rd., Shanghai 200433, China. 20. Huaxi Hospital of Sichuan University, No. 37, Guo Xue Xiang, Chengdu 610041, China. 21. Peking University First Hospital, No. 8, Xicheng Xishiku Street, Beijing 100034, China. 22. Henan Provincial People's Hospital, No. 7, Weiwu Rd., Zhengzhou 450003, China. 23. University Malaya Medical Centre, Malaysia, Clinical Investigation Centre, 13th Floor, Main Tower, University Malaya Medical Centre, Lembah Pantai 59100, Malaysia. 24. Medical Clinic One, Mount Elizabeth Medical Centre, Singapore, #17-02, 3 Mt. Elizabeth, 228510 Singapore, Singapore. 25. Far Eastern Memorial Hospital, Taiwan, No. 21, Sec. 2, Nanya S. Rd., Banciao District, New Taipei City 22060, Taiwan. 26. Mackay Memorial Hospital, Taiwan, 92, Section 2, Chung Shan North Rd., Taipei City 10449, Taiwan. 27. Merck, Sharp & Dohme, Shanghai, China, 20/F Park Place, 1601 Nanjing Rd. (w), Shanghai 200040, China. 28. Beijing Ditan Hospital, Capital Medical University, No. 8, East Jingshun Street, Beijing 100015, China. Electronic address: xudaozhen@126.com.
Abstract
BACKGROUND: In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0μg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B. OBJECTIVE: This multicenter, randomized trial evaluated the safety and efficacy of regimens utilizing increased dose or treatment duration in treatment-naive Chinese patients with chronic hepatitis B. STUDY DESIGN: 670 HBeAg-positive patients from China, Malaysia, Taiwan area, Singapore, and Thailand were enrolled. Patients received PEG-IFN alfa-2b 1.0μg/kg/wk (arm A) or 1.5μg/kg/wk (arm B) for 24 weeks, or 1.5μg/kg/wk for 48 weeks (arm C). The primary end point was loss of HBeAg 24 weeks after end of treatment. RESULTS: At the end of follow-up, HBeAg loss was significantly greater in arm C compared with arm A (31.3% vs. 17.3%; P=0.001) and arm B (31.3% vs. 18.1%; P=0.001). No significant difference in the rate of HBeAg loss was observed between arms A and B. The proportions of patients with HBe seroconversion, HBV DNA levels <20,000IU/mL, and ALT normalization at the end of follow-up were significantly higher in arm C compared with arm A and arm B. In arms A, B, and C, rates of early treatment discontinuation were 6.3%, 4.9%, and 8.9%; of discontinuation due to an AE, 2%, 3%, and 3%; and of AEs requiring dose modification, 3%, 6%, and 10%, respectively. CONCLUSIONS: In Chinese patients with HBeAg-positive chronic hepatitis B, PEG-IFNalfa-2b 1.5μg/kg/wk for 48 weeks is more efficacious compared with 1.0 and 1.5μg/kg/wk for 24 weeks.
RCT Entities:
BACKGROUND: In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0μg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B. OBJECTIVE: This multicenter, randomized trial evaluated the safety and efficacy of regimens utilizing increased dose or treatment duration in treatment-naive Chinese patients with chronic hepatitis B. STUDY DESIGN: 670 HBeAg-positive patients from China, Malaysia, Taiwan area, Singapore, and Thailand were enrolled. Patients received PEG-IFN alfa-2b 1.0μg/kg/wk (arm A) or 1.5μg/kg/wk (arm B) for 24 weeks, or 1.5μg/kg/wk for 48 weeks (arm C). The primary end point was loss of HBeAg 24 weeks after end of treatment. RESULTS: At the end of follow-up, HBeAg loss was significantly greater in arm C compared with arm A (31.3% vs. 17.3%; P=0.001) and arm B (31.3% vs. 18.1%; P=0.001). No significant difference in the rate of HBeAg loss was observed between arms A and B. The proportions of patients with HBe seroconversion, HBV DNA levels <20,000IU/mL, and ALT normalization at the end of follow-up were significantly higher in arm C compared with arm A and arm B. In arms A, B, and C, rates of early treatment discontinuation were 6.3%, 4.9%, and 8.9%; of discontinuation due to an AE, 2%, 3%, and 3%; and of AEs requiring dose modification, 3%, 6%, and 10%, respectively. CONCLUSIONS: In Chinese patients with HBeAg-positive chronic hepatitis B, PEG-IFN alfa-2b 1.5μg/kg/wk for 48 weeks is more efficacious compared with 1.0 and 1.5μg/kg/wk for 24 weeks.