[EASL2013]HCV三联方案具有较高的治愈率

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在2013年欧洲肝病学会（European Association for the Study of the Liver,EASL）主办的国际肝病大会（the International Liver Congress,ILC）上，一项2期随机研究发现，无干扰素和利巴韦林的三联方案——DCV+ASV+BMS-791325有较高的丙型肝炎病毒（HCV）治愈率和安全性。

        这项研究共招募66例患者，研究人员将初治的HCV GT1，非肝硬化患者（n=32）以1:1的比例随机分配，接受DCV 60mg qd，ASV 200mg bid，和BMS-791325 75mg,为期24周（组1）或12周（2组）。另外34例患者被随机分配接受DCV, ASV和BMS-791325 150mg bid分别治疗24周(组3)或12周(组4)。主要终点是12周治疗后HCV RNA＜25 IU/ml（SVR12）。提交组1（SVR12），组2（SVR24），组3（SVR4），组4（SVR4）和（SVR12）的安全性和SVR数据。

        受试者主要是GT1a型（74%），白人（79%），IL28B-非CC（70%）。在第4周时，66例中有64例的HCV RNA＜25 IU/ml。中期分析中发现，治疗12周和24周的病毒学应答无明显差异。总的来说，92%的病人获得了SVR4（46/50），94%的病人获得了SVR12（30/32），94%的获得了SVR24（15/16）。服用BMS-791325 150mg的患者有3例失败（组3-4）（2例病毒学突破，1例复发）。没有患者因对DCV + ASV + BMS-791325相关的不良事件（AES）停止治疗。最常见的不良事件（≥10%）是头痛，乏力，和胃肠道反应。两个严重不良事件的报道，都与DCV + ASV + BMS-791325无关。没有肝毒性或血清ALT/AST或胆红素升高的报告。

       在对初治GT1患者的治疗中发现，DCV+ASV+BMS-791325获得了很高的SVR4，SVR12和SVR24率。该方案的耐受性良好，没有明显的安全性问题。目前进行的扩展研究是为了更好的确定该方案的有效性和安全性。

论文摘要：

Interim analysis of an interferon (ifn)- and ribavirin (rbv)-free regimen of daclatasvir (dcv), asunaprevir (asv), and bms-791325 in treatment-naive, hepatitis c virus genotype 1-infected patients

Background and Aims: The IFN- and RBV-free regimen of DCV(NS5A inhibitor), ASV (protease inhibitor) and BMS-791325 (nonnucleoside NS5B inhibitor, 75mg BID) for 24 or 12 weeks was well tolerated and achieved SVR4 and SVR12 >90% in treatment-naive,hepatitis C virus (HCV) genotype (GT) 1 patients. We present safety and SVR following 24 or 12 weeks of this treatment using two BMS-791325 doses (75 vs 150mg BID).

Methods: This phase 2 study randomized treatment-naive, HCV GT1, non-cirrhotic patients (N = 32) 1:1 to DCV 60mg QD, ASV 200mg BID, and BMS-791325 75mg BID for 24 (Group 1) or 12 (Group 2) weeks. Following safety evaluation, 34 additional
patients were randomized to DCV, ASV, and BMS-791325 150mg BID for 24 (Group 3) or 12 (Group 4) weeks. The primary end
point was HCVRNA< 25 IU/mL at 12 weeks post-treatment (SVR12). Safety and SVR from Groups 1 (SVR12), 2 (SVR24) and 4 (SVR4) are described, Groups 3 (SVR4) and 4 (SVR12) will be presented.

Results: Patients were mainly GT1a (74%), white race (79%), and IL28B non-CC (70%). 64 of 66 patients had HCVRNA < 25 IU/mL by Week 4 (Table). In this interim analysis, there was no difference in virologic responses between 12 and 24 weeks of treatment. Overall, patients achieved SVR4 92% (46/50), SVR12 94% (30/32), and SVR24 94% (15/16) (Table). Three failures (Groups 3–4) were observed in patients receiving BMS-791325 150mg (2-viral breakthrough,1-relapse). No patients discontinued due to adverse events (AEs) related to DCV+ASV+BMS-791325. Most common AEs (≥10% total) were headache, asthenia, and gastrointestinal. Two serious AEs have been reported, both unrelated to DCV+ASV+BMS-791325. No hepatotoxicity or Grade 3/4 elevations of ALT/AST or bilirubin were reported.

Conclusion: DCV+ASV+BMS-791325 achieved high rates of SVR4, SVR12, and SVR24 in treatment-naive GT1 patients, characterized by GT1a and IL28B non-CC. This regimen was well tolerated with no apparent safety signals. Expansion of the current study is underway to better define the efficacy and safety of this regimen.

hao.k.h

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