Jian Sun1, Hong Ma2, Qing Xie3, Yao Xie4, Yongtao Sun5, Hao Wang6, Guangfeng Shi7, Mobin Wan8, Junqi Niu9, Qin Ning10, Yanyan Yu11, Huijuan Zhou3, Jun Cheng4, Wenzhen Kang5, Yi Xie12, Rong Fan1, Lai Wei6, Hui Zhuang13, Jidong Jia2, Jinlin Hou14. 1. State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangdong Province, China. 2. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, Xicheng District, China. 3. Department of Infectious Diseases, Shanghai Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China. 4. Liver Disease Department, Beijing DiTan Hospital, Beijing, Chongyang District, China. 5. Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province, China. 6. Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China. 7. Department of Infectious Diseases, Huashan Hospital affiliated to Fudan University, Shanghai, China. 8. Department of Infectious Diseases, Shanghai Changhai Hospital, Shanghai, China. 9. Department of Liver, First Hospital of Jilin University, Changchun, Jilin Province, China. 10. Department of Infectious Diseases, Wuhan Tongji Hospital affiliated to Huazhong Technology University, Tongji Medical College, Wuhan, Hubei Province, China. 11. Department of Infectious Diseases, Peking University First Hospital, Beijing, China. 12. Shanghai Roche Pharmaceuticals Co Ltd, Shanghai, China. 13. Department of Microbiology and Infectious Disease Center, Peking University, Health Science Center, Beijing, China. 14. State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangdong Province, China. Electronic address: jlhousmu@163.com.
Abstract
BACKGROUND & AIMS: Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the pegylated interferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B. METHODS: In this open-label, multicenter, randomized trial, HBeAg positive patients were treated with PegIFN (180μg/week) for 24weeks. Early responders (HBsAg <1500IU/ml and HBV DNA <10(5)copies/ml at week 24) received PegIFN for a further 24weeks (arm A), while non-early responders were randomized to PegIFN for another 24weeks (arm B), another 72weeks (arm C) or PegIFN for another 72weeks plus adefovir for 36weeks (arm D). The primary endpoint was the change of quantitative HBsAg from baseline to the end of follow-up (EOF). RESULTS: For non-early responders, 96-week PegIFN monotherapy did not lead to a greater reduction of HBsAg from baseline to EOF, compared with 48-week PegIFN (-0.71 vs. -0.67log10IU/ml, P=0.407). The rate of HBeAg seroconversion with HBV DNA <2000IU/ml at EOF were similar for arms B, C and D (17.9%, 23.9% and 25.0% respectively). For patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24, 38.4% and 37.0% achieved HBeAg seroconversion with HBV DNA <2000IU/ml at EOF respectively. CONCLUSIONS: Patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24 would benefit from continued PegIFN treatment. Extending the duration of PegIFN with or without adding adefovir did not show superiority over 48weeks PegIFN monotherapy. LAY SUMMARY: Extending the duration of pegylated interferon (PegIFN) alfa-2a is not recommended in HBeAg positive patients as treatment extension beyond 48weeks did not show convincing benefit. Patients who achieved HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml after 24-week PegIFNα-2a showed satisfactory outcome after the withdrawal of finite PegIFNα-2a treatment. CLINICAL TRIAL NUMBER: NCT01086085.
RCT Entities:
BACKGROUND & AIMS: Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the pegylated interferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B. METHODS: In this open-label, multicenter, randomized trial, HBeAg positive patients were treated with PegIFN (180μg/week) for 24weeks. Early responders (HBsAg <1500IU/ml and HBV DNA <10(5)copies/ml at week 24) received PegIFN for a further 24weeks (arm A), while non-early responders were randomized to PegIFN for another 24weeks (arm B), another 72weeks (arm C) or PegIFN for another 72weeks plus adefovir for 36weeks (arm D). The primary endpoint was the change of quantitative HBsAg from baseline to the end of follow-up (EOF). RESULTS: For non-early responders, 96-week PegIFN monotherapy did not lead to a greater reduction of HBsAg from baseline to EOF, compared with 48-week PegIFN (-0.71 vs. -0.67log10IU/ml, P=0.407). The rate of HBeAg seroconversion with HBV DNA <2000IU/ml at EOF were similar for arms B, C and D (17.9%, 23.9% and 25.0% respectively). For patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24, 38.4% and 37.0% achieved HBeAg seroconversion with HBV DNA <2000IU/ml at EOF respectively. CONCLUSIONS:Patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24 would benefit from continued PegIFN treatment. Extending the duration of PegIFN with or without adding adefovir did not show superiority over 48weeks PegIFN monotherapy. LAY SUMMARY: Extending the duration of pegylated interferon (PegIFN) alfa-2a is not recommended in HBeAg positive patients as treatment extension beyond 48weeks did not show convincing benefit. Patients who achieved HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml after 24-week PegIFNα-2a showed satisfactory outcome after the withdrawal of finite PegIFNα-2a treatment. CLINICAL TRIAL NUMBER: NCT01086085.