第65届美国肝病学会年会（AASLD2014）上将要发布的一项国际性的III期临床试验中，比较了daclatasvir (DCV; 全基因型 NS5A 抑制剂), asunaprevir (ASV; NS3 蛋白酶抑制剂), 和BMS-791325 ('325; 非核苷 NS5B 3DAA）全口服药联合治疗方案±利巴韦林(RBV)在治疗初治和经治的1型丙型肝炎病毒感染合并代偿性肝硬化患者的疗效。

研究方法

患者被随机分配到DCV 30 mg, ASV 200 mg, 和 '325 75 mg的固定剂量复合剂+利巴韦林/安慰剂组；每日2次，治疗12个周。我们分别评估了初治和经治患者的12周时的持续病毒学应答率作为关键的疗效预后评价指标。

研究结果

初治和经治的肝硬化患者的12周时的持续病毒学应答率结果见下表。13位(6%)患者抗病毒治疗失败。初治(N=112)和经治(N=90)的患者基础特点相似。所有患者中，66%为男性，27%为IL28B (rs1297860) CC基因型。74%的患者存在GT1 a感染，26%的患者存在GT1b感染。有3种与治疗有关的严重不良反应。1例不良反应导致停用3DAA，未导致患者死亡。最常见的不良反应是疲劳、头痛、恶心、腹泻、失眠和瘙痒。利巴韦林组中5%的患者治疗后血红蛋白<9 g/dL，而对照组患者未出现这种现象。

结论

在202位GTI感染的肝硬化的患者中，应用DCV/ASV/BMS 791325 FDC全口服治疗，无论是否联用利巴韦林，12周持续病毒应答率都很高。这些结果表明，DCV 3DAA方案在治疗代偿性肝硬化的患者时，可能抗病毒活性，耐受性和安全性较好。

英文摘要原文

All-oral fixed-dose combination therapy with daclatasvir/asunaprevir/BMS-791325 +/- ribavirin, for patients with HCV genotype 1 infection and compensated cirrhosis: UNITY-2 Phase 3 SVR12 results

Introduction: The all-oral combination of daclatasvir (DCV; pangenotypic NS5A inhibitor), asunaprevir (ASV; NS3 protease inhibitor), and BMS-791325 ('325; non-nucleoside NS5B 3DAA regimen—was studied with and without ribavirin (RBV) in treatment-naive and treatment-experienced patents with HCV genotype (GT) 1 infection and compensated cirrhosis in a Phase 3, international clinical trial. 

Methods: Patients were randomly assigned to rece.ve a fixed-dose combination (FDC) of DCV 30 mg, ASV 200 mg, and '325 75 mg, with blinded RBV or placebo, twice-daily for 12 weeks. SVR12 rates in the treatment-na.ve and experienced cohorts were evaluated separate y as key efficacy outcomes.

Results: SVR12 results in treatment-na.ve and -experienced cirrhotic patients are in the table below. Virologic failure was observed in 13 (6%) patients. Baseline characteristics were comparable between treatment-naive (N=112) and treatment-experienced (N=90) groups. Overall, patients were 66% ma e and 27% IL28B (rs1297860) CC genotype; 74% of patients had G Tla infection and 26% had G T 1b. There were 3 serious adverse events (SAEs) considered related to treatment, 1 AE leading to 3DAA discontinuation, and no deaths. The most frequent AES (»10% of patients) were fatigue, headache, nausea, diarrhea, insomnia and pruritus. Hemoglobin g/dL on treatment was observed in 5% of patients in the RBV-containing cohorts but in no patients in the RBV-free cohorts. 

Conclusions: Twelve weeks of all-oral treatment with DCV/ASV/BMS 791325 FDC, with or without ribavirin, achieved high rates of SVR12 in 202 cirrhotic patients with GTI infection. These results demonstrate the potent antiviral activity, tolerability and safety of the DCV 3DAA regimen in patients with compensated cirrhosis. 

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