Ide Kazuki, Sato Izumi, Imai Takumi, Hawke Philip, Yamada Hiroshi, Kawasaki Yohei, Masaki Naohiko
Department of Drug Evaluation & Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka.
Biol Pharm Bull. 2016 Dec 1;39(12):2060-2065. doi: 10.1248/bpb.b16-00617. Epub 2016 Sep 17.
This study compares the safety profiles of pegylated interferon (PEG-IFN) α-2a and α-2b administered in combination with ribavirin, based on the variable of time to withdrawal from treatment due to adverse events. We conducted a real-world retrospective cohort study using the Japanese interferon database. Based on eligibility criteria, individuals with chronic hepatitis C virus (HCV) infection were identified in the database covering the period December 2009 to August 2015. The primary outcome measure was defined as difference in time to withdrawal from treatment due to adverse events between patients receiving PEG-IFN α-2a combined with ribavirin and those receiving PEG-IFN α-2b combined with ribavirin. The difference was analyzed using the multivariate Cox proportional hazards regression model. A frailty model was also applied to consider regional (prefectural) variation. After eligibility evaluation, 11058 individuals were included in the analysis. 3774 were treated with PEG-IFN α-2a, and 6764 with PEG-IFN α-2b, with 11.84 and 12.30% respectively withdrawing from treatment due to adverse events. The Cox model showed no significant difference between the two groups (hazard ratio (HR), 95%CI; 0.918, 0.817 to 1.031; p=0.1475). The results were consistent even when regional variation and other confounding variables were adjusted in the frailty model. In conclusion, there may be no difference in time to withdrawal from treatment due to adverse events between PEG-IFN α-2a and PEG-IFN α-2b combined with ribavirin. Applying the method used here to future studies using novel treatment regimens may also provide important information for the treatment of chronic HCV infection in clinical practice.
本研究基于因不良事件而停药的时间变量，比较了聚乙二醇化干扰素（PEG-IFN）α-2a与α-2b联合利巴韦林治疗的安全性。我们使用日本干扰素数据库进行了一项真实世界回顾性队列研究。根据纳入标准，在涵盖2009年12月至2015年8月期间的数据库中识别出慢性丙型肝炎病毒（HCV）感染者。主要结局指标定义为接受PEG-IFNα-2a联合利巴韦林治疗的患者与接受PEG-IFNα-2b联合利巴韦林治疗的患者因不良事件而停药的时间差异。使用多变量Cox比例风险回归模型分析该差异。还应用了脆弱模型来考虑地区（县）差异。经过纳入标准评估，11058人纳入分析。3774人接受PEG-IFNα-2a治疗，6764人接受PEG-IFNα-2b治疗，分别有11.84%和12.30%因不良事件停药。Cox模型显示两组之间无显著差异（风险比（HR），95%CI：0.918，0.817至1.031；p = 0.1475）。即使在脆弱模型中对地区差异和其他混杂变量进行调整后，结果仍然一致。总之，PEG-IFNα-2a与PEG-IFNα-2b联合利巴韦林治疗因不良事件而停药的时间可能没有差异。将此处使用的方法应用于未来使用新型治疗方案的研究中，也可能为临床实践中慢性HCV感染的治疗提供重要信息。
