Y型聚乙二醇干扰素α-2b注射液治疗HCV基因2/3型慢性丙型肝炎患者疗效和安全性的多中心随机对照试验研究*

目的 以标准剂量的聚乙二醇干扰素（PegIFN）α-2a联合利巴韦林作为阳性对照,评价新型试验药物Y型PegIFNα-2b注射液联合利巴韦林治疗2型/3型慢性丙型肝炎（CHC）患者的疗效和安全性。方法 采用多中心、随机开放、阳性药对照的Ⅲ期临床试验,筛选符合要求的2型/3型CHC患者,按照2:1的比例随机分配到Y型PegIFNα-2b组和PegIFNα-2a组,同时口服利巴韦林,疗程24 w,停药随访24 w。采用Abbott RealTime HCV Genotype II检测HCV基因型,采用Cobas TaqMan实时定量PCR法检测血清HCV RNA水平。详细记录不良事件。主要疗效指标为持续病毒学应答（SVR）,并进行非劣效检验。结果 本试验实际入组2型/3型CHC患者255例,实际治疗241例。全分析集（FAS）数据显示,158例试验组和83例对照组患者SVR分别为85.4%（95% CI 79.94%~90.94%）和79.5%（95% CI 70.84%~88.20%,P=0.2402）;对符合方案分析集（PPS）人群分析显示,试验组和对照组患者SVR分别为87.9%（95% CI 82.45%~93.27%）和85.9%（95% CI 77.82%~94.01%,P=0.7060）,率差的95%可置信区间均符合非劣效标准;对PPS人群分析显示,85.8%受试者获得了早期病毒学应答（RVR）,RVR的阳性预测值为90.1%;试验组和对照组不良事件发生率相似,分别为95.6%和95.2%,严重不良事件发生率分别为3.8%和3.6%。结论 应用PegIFNα联合利巴韦林治疗2型/3型CHC患者,新型试验药物Y型PegIFNα-2b具有与对照药物PegIFNα-2a相似的疗效和安全性。

Efficacy and safety of type Y pegylated interferon α-2b in the treatment of patients with chronic hepatitis C virus genotypes 2/3 infection: a randomized,PegIFNα-2a-controlled phase III clinical trial

Objective To investigate the efficacy and safety of type Y pegylated interferon α-2b （YPegIFNα-2b,40kD） in the treatment of patients with chronic hepatitis C virus genotypes 2/3 infection in a randomized,PegIFNα-2a-controlled phase III clinical trial. Methods A multi-center,randomized,open-label and positive controlled phase III clinical trial was conducted in this study. Chronic hepatitis C （CHC） patients who met inclusion criteria were randomly allocated in a ratio of 2:1 to 2 cohorts and treated with YPegIFNα-2b or PegIFNα-2a（180 μg）,respectively,and ribavirin for 24 weeks,and they were all followed-up for 24 weeks after discontinuation of the regimen. The primary efficacy was assessed by sustained virological response （SVR）. Results Two hundred fifty-five participants with genotypes 2 or 3 HCV infection were enrolled. Intention-to-treat analysis showed that SVR were 85.4%（95% CI 79.94%-90.94%） and 79.5% （95% CI 70.84%-88.20%） in patients treated with YPegIFNα-2b and PegIFNα-2a,respectively（P=0.2402）;95% confidence intervals of rate difference conformed to standard of non-inferiority. Positive predictive value of rapid virological response for SVR was 90.1%;Additionally,there were no significant differences in adverse effects（95.6% vs. 95.2%） and severe adverse effects（3.8% vs. 3.6%） between the YPegIFNα-2b- and control agent-treated patients with CHC. Conclusions YPegIFNα-2b provides an alternative efficacious treatment option in patients with chronic HCV genotypes 2/3 infection as its similar efficacy and safety to PegIFNα-2a in this pilot clinical trial.