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

• DOI: 10.3760/cma.j.issn.1007-3418.2017.08.007
• Publication Date: 2017-08-20
• Authors: Feng-Qin Hou; Yulong Yin; Li Zeng; Jing Shang; Gaoming Gong; Chunqin Pan; Mingxiang Zhang; Chibiao Yin; Qing Xie; Yiqiang Peng; Shengli Chen; Qing Mao; Ya Chen; Mao Qian-guo; D Z Zhang; Tao Han; M R Wang; Weiming Zhao; Jingbang Liu; Ying Han; Lijing Zhao; Guangwei Luo; J M Zhang; Jie Peng; Dianhui Tan; Zhengrui Li; Hong Tang; Hui Wang; Y X Zhang; Juanjuan Li; L L Zhang; L Chen; Jidong Jia; C W Chen; Ziyi Zhen; Bowen Li; Jun Niu; Qinghua Meng; Hui Yuan; Yongtao Sun; Su‐Chen Li; Jifang Sheng; Jun Cheng; Liping Sun; G Q Wang
• Keywords: HBeAg; Pegylated interferon; Seroconversion; Hepatitis B

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 treatment 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, positive-controlled phase III trial. Eligible CHB patients were screened out randomized to Peg-IFN-α-2b trial group control at ratio 2:1. The course 48 weeks followed up for 24 after drug withdrawal. Plasma samples collected screening, baseline, 12, 24, 36, 48, 60, 72 centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test used measure DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay Elecsys kit markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events recorded detail. primary outcome HBeAg seroconversion rate 24-week follow-up, non-inferiority also tested. difference between two-sided confidence interval (CI) calculated, demonstrated if lower limit 95% CI > -10%. t-test, chi-square test, or rank sum test according types features data. Results: A total 855 enrolled 820 them received (538 282 group). data full analysis set showed that week 27.32% 22.70% 4.63% (95% -1.54% 10.80%, P = 0.1493). per-protocol 30.75% 27.14% 3.61% -3.87% 11.09%, 0.3436). met criteria, non-inferior group. two groups had similar incidence rates adverse events, serious common events. Conclusion: In Peg-IFN-α regimen new has comparable Peg-IFN-α-2a.目的： 以标准剂量聚乙二醇干扰素α-2a（Peg-IFN α-2a）作为阳性药对照，评价长效干扰素Peg-IFN α-2b （Y型，40 kD）注射液（180 μg/周）治疗HBeAg阳性慢性乙型肝炎（CHB）患者的疗效和安全性。 方法： 多中心、随机开放、阳性药平行对照的III期临床试验。筛选合格的HBeAg阳性CHB患者按照2∶1随机分配到Peg-IFN α-2b（Y型，40 kD）组（试验组）和Peg-IFN α-2a组（对照组），治疗48周，停药随访24周。在筛选、基线、12周、24周、48周，60周和72周时保留受试者血浆用于中心化检测，用COBAS(®) Ampliprep/COBAS(®) TaqMan(®) Test，Version 2.0荧光定量PCR检测HBV DNA定量，用Elecsys试剂盒电化学发光免疫分析法检测HBV标志物(HBsAg、抗-HBs、HBeAg、抗-HBe)。详细记录不良事件。主要疗效指标为治疗48周随访24周后的HBeAg血清学转换率，并进行非劣效检验。计算两组治疗后HBeAg血清转换率差值（试验组-对照组）及其双侧95%可信区间（CI），当95% CI的下限大于-10%时，非劣效结论成立。根据不同的数据类型及特点分别采用t检验、χ(2)检验、秩和检验等。 结果： 入组HBeAg阳性CHB患者855例，实际治疗820例（试验组538例，对照组282例）。全分析集数据显示，试验组和对照组的72周HBeAg血清学转换率分别为27.32%和22.70%，率差为4.63%，95% CI：-1.54%~10.80%，P 0.149 3。符合方案分析集数据显示，试验组与对照组的HBeAg血清学转换率分别为30.75%和27.14%，率差为3.61%，95% CI：-3.87%~11.09%，P 0.343 6。95% CI符合非劣效标准，试验组非劣效于对照组。试验组与对照组整体不良事件、严重不良事件及常见不良事件发生率均相似。 结论： Peg-IFN α治疗HBeAg阳性CHB患者的方案中，新药Peg-IFN kD）具有与对照药Peg-IFN α-2a相当的疗效和安全性。.