Clinical effect and safety of pegylated interferon-α-2b injection (Y shape, 40 kD) in treatment of HBeAg-positive chronic hepatitis B patients

作者：Hou Fengqin; Yin Yalin; Zeng Lingying; Shang Jia; Gong Guozhong; Pan Chen; Zhang Mingxiang; Yin Chibiao; Xie Qing; Peng Yanzhong; Chen Shijun; Mao Qing; Chen Yongping; Mao Qianguo; Zhang Dazhi; Han Tao; Wang Maorong; Zhao Wei; Liu Jiajun; Han Ying; Zhao Longfeng; Luo Guanghan; Zhang Jiming; Peng Jie; Tan Deming; Li Zhiwei; Tang Hong; Wang Hao; Zhang Yuexin; Li Jun; Zhang Lunli; Chen Liang; Jia Jidong; Chen Chengwei; Zhen Zhen; Li Baosen; Niu Junqi; Meng Qinghua; Yuan Hong; Sun Yongtao

来源：中华肝脏病杂志, 2017, 25(8).

DOI：10.3760/cma.j.issn.1007-3418.2017.08.007

• Hepatitis B,chronic
• Peginterferon
• HBeAg seroconversion
• Clinical trial

Objective To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape,40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients,with standard-dose Peg-IFN-α-2a as positive control.Methods This study was a multicenter,randomized,open-label,and positive-controlled phase Ⅲ clinical trial.Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape,40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2∶1.The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal.Plasma samples were collected at screening,baseline,and 12,24,36,48,60,and 72 weeks for centralized detection.COBAS(R) Ampliprep/COBAS(R) TaqMan(R) HBV Test was used to measure HBV DNA level by quantitative real-time PCR.Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg,anti-HBs,HBeAg,anti-HBe).Adverse events were recorded in detail.The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up,and non-inferiority was also tested.The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated,and non-inferiority was demonstrated if the lower limit of 95％ CI was ＞-10％.The t-test,chi-square test,or rank sum test was used according to the types and features of data.Results A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group).The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32％ in the trial group and 22.70％ in the control group with a rate difference of 4.63％ (95％ CI-1.54％ to 10.80％,P =0.1493).The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75％ in the trial group and 27.14％ in the control group with a rate difference of 3.61％ (95％ CI-3.87％ to 11.09％,P =0.3436).95％ CI met the non-inferiority criteria,and the trial group was non-inferior to the control group.The two groups had similar incidence rates of adverse events,serious adverse events,and common adverse events.Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients,the new drug Peg-IFN-α-2b (Y shape,40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

• 单位
  北京大学