Butt A A, Yan P, Shaikh O S, Freiberg M S, Lo Re V, Justice A C, Sherman K E
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
J Viral Hepat. 2015 Sep;22(9):691-700. doi: 10.1111/jvh.12375. Epub 2014 Dec 18.
Effectiveness, safety and tolerability of boceprevir (BOC) and telaprevir (TPV) in actual clinical settings remain unknown. We determined rates of sustained virologic response (SVR) and haematologic adverse effects among persons treated with BOC- or TPV-containing regimens, compared with pegylated interferon/ribavirin (PEG/RBV). Using an established cohort of hepatitis C virus (HCV)-infected persons, Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), we identified those treated with a BOC- or TPV-containing regimen and HCV genotype 1-infected controls treated with PEG/RBV. We excluded those with HIV coinfection and missing HCV RNA values to determine SVR. Primary endpoints were SVR (undetectable HCV RNA ≥12 weeks after treatment completion) and haematologic toxicity (grade 3/4 anaemia, neutropenia and thrombocytopenia). We evaluated 2288 persons on BOC-, 409 on TPV-containing regimen and 6308 on PEG/RBV. Among these groups, respectively, 31%, 43% and 9% were treatment-experienced; 17%, 37% and 14% had baseline cirrhosis; 63%, 54% and 48% were genotype 1a. SVR rates among noncirrhotics were as follows: treatment naïve: 65% (BOC), 67% (TPV) and 31% (PEG/RBV); treatment experienced: 57% (BOC), 54% (TPV) and 13% (PEG/RBV); (P-value not significant for BOC vs TPV; P < 0.0001 for BOC or TPV vs PEG/RBV). Haematologic toxicities among BOC-, TPV- and PEG/RBV-treated groups were as follows: grade 3/4 anaemia 7%, 11% and 3%; grade 4 thrombocytopenia 2.2%, 5.4% and 1.7%; grade 4 neutropenia 8.2%, 5.6% and 3.4%. SVR rates are higher and closer to those reported in pivotal clinical trials among BOC- and TPV-treated persons compared with PEG/RBV-treated persons. Haematologic adverse events are frequent, but severe toxicity is uncommon.
博赛匹韦（BOC）和替拉匹韦（TPV）在实际临床环境中的有效性、安全性和耐受性尚不清楚。我们确定了接受含BOC或TPV方案治疗的患者与接受聚乙二醇干扰素/利巴韦林（PEG/RBV）治疗的患者相比的持续病毒学应答（SVR）率和血液学不良反应。利用一个已建立的丙型肝炎病毒（HCV）感染患者队列，即电子检索的HCV感染退伍军人队列（ERCHIVES），我们确定了接受含BOC或TPV方案治疗的患者以及接受PEG/RBV治疗的HCV基因1型感染对照。我们排除了合并HIV感染和HCV RNA值缺失的患者以确定SVR。主要终点是SVR（治疗完成后≥12周HCV RNA检测不到）和血液学毒性（3/4级贫血、中性粒细胞减少和血小板减少）。我们评估了2288例接受BOC治疗的患者、409例接受含TPV方案治疗的患者和6308例接受PEG/RBV治疗的患者。在这些组中，分别有31%、43%和9%的患者有治疗史；17%、37%和14%的患者有基线肝硬化；63%、54%和48%的患者为基因1a型。非肝硬化患者的SVR率如下：初治患者：65%（BOC）、67%（TPV）和31%（PEG/RBV）；有治疗史患者：57%（BOC）、54%（TPV）和13%（PEG/RBV）；（BOC与TPV相比P值无显著性差异；BOC或TPV与PEG/RBV相比P<0.0001）。接受BOC、TPV和PEG/RBV治疗的组中的血液学毒性如下：3/4级贫血分别为7%、11%和3%；4级血小板减少分别为2.2%、5.4%和1.7%；4级中性粒细胞减少分别为8.2%、5.6%和3.4%。与接受PEG/RBV治疗的患者相比，接受BOC和TPV治疗的患者的SVR率更高，且更接近关键临床试验中报告的率。血液学不良事件很常见，但严重毒性并不常见。
