Toronto Centre for Liver Disease, McLaughlin-Rotman Centre for Global Health, Toronto, ON, Canada.
Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, NY, USA.
J Hepatol. 2015 Feb;62(2):294-302. doi: 10.1016/j.jhep.2014.09.013. Epub 2014 Sep 18.
BACKGROUND & AIMS: Chronic hepatitis C treatment for prior non-responders to peginterferon (PegIFN)/ribavirin remains suboptimal. The MATTERHORN study evaluated regimens containing ritonavir-boosted danoprevir (danoprevir/r) in prior PegIFN alfa/ribavirin non-responders.
Prior partial responders (N=152) were randomized to 24 weeks of twice-daily danoprevir/r 100/100mg, mericitabine 1000 mg and ribavirin 1000/1200 mg (IFN-free); danoprevir/r plus PegIFN alfa-2a/ribavirin (triple); or danoprevir/r, mericitabine and PegIFN alfa-2a/ribavirin (Quad). Prior null responders (N=229) were randomized to 24 weeks of IFN-free therapy, or quad alone (Quad 24) or quad plus 24-weeks of PegIFN alfa-2a/ribavirin (Quad 48). The primary endpoint was sustained virological response (HCV RNA <25 IU/ml) 24 weeks after end-of-treatment (SVR24). Due to high relapse rates, genotype (G) 1a patients in IFN-free arms were offered additional PegIFN alfa-2a/ribavirin.
Among prior partial responders, SVR24 rates were 46.2%, 51.0%, and 86.0%, in the IFN-free, Triple and Quad arms, respectively; among prior null responders, SVR24 rates were 45.5%, 80.5%, and 83.8% respectively. Relapse rates were lower and SVR24 rates higher in G1b-infected than G1a-infected patients. SVR24 rates in G1a and G1b patients randomized to Quad were 75.0% and 96.2%, respectively, in the partial Quad arm, and 68.1% and 100%, respectively, in the null Quad 24 arm. Treatment failure was associated with resistance to danoprevir, but not to mericitabine, and was more common in G1a infected patients. Treatment was well-tolerated.
Danoprevir/r, mericitabine plus PegIFN alfa-2a/ribavirin was well-tolerated and produced high overall SVR24 rates in prior partial and null responders to PegIFN alfa/ribavirin. In contrast, IFN-free regimens were associated with unacceptably high relapse rates.
先前对聚乙二醇干扰素（PegIFN）/利巴韦林无应答的慢性丙型肝炎患者的治疗效果仍不理想。MATHORNE 研究评估了含利托那韦增强型达诺瑞韦（danoprevir/r）的方案在先前 PegIFN α/利巴韦林无应答者中的疗效。
先前部分应答者（N=152）随机分为 24 周每日两次达诺瑞韦/r 100/100mg、美替拉韦 1000mg 和利巴韦林 1000/1200mg（无干扰素）；达诺瑞韦/r 加 PegIFN α-2a/利巴韦林（三联）；或达诺瑞韦/r、美替拉韦和 PegIFN α-2a/利巴韦林（四联）。先前无应答者（N=229）随机分为 24 周无干扰素治疗，或四联单药（四联 24 周）或四联加 24 周 PegIFN α-2a/利巴韦林（四联 48 周）。主要终点是治疗结束后 24 周时持续病毒学应答（HCV RNA<25 IU/ml）（SVR24）。由于复发率高，无干扰素组的基因型（G）1a 患者被给予额外的 PegIFN α-2a/利巴韦林。
在先前的部分应答者中，无干扰素、三联和四联组的 SVR24 率分别为 46.2%、51.0%和 86.0%；在先前的无应答者中，SVR24 率分别为 45.5%、80.5%和 83.8%。G1b 感染患者的复发率较低，SVR24 率较高。在 G1a 和 G1b 患者中，随机分配至四联的患者中，SVR24 率分别为 75.0%和 96.2%，在部分四联组中为 68.1%和 100%，在无干扰素四联 24 周组中为 68.1%和 100%。治疗失败与对达诺瑞韦的耐药性相关，但与美替拉韦无关，并且在 G1a 感染患者中更为常见。治疗耐受性良好。
达诺瑞韦/r、美替拉韦联合 PegIFN α-2a/利巴韦林在先前对 PegIFN α/利巴韦林无应答的部分和完全无应答者中耐受性良好，总体 SVR24 率较高。相比之下，无干扰素方案的复发率过高。
