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

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® Ampliprep/COBAS® TaqMan® 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.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(®) HBV 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 α-2b （Y型，40 kD）具有与对照药Peg-IFN α-2a相当的疗效和安全性。.