Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection
Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection
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DOI：
10.1056/nejmoa1613512
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发表时间：
2017-06-01
影响因子：
158.5
通讯作者：
Zeuzem, S.
中科院分区：
文献类型：
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作者：
Bourliere, M.;Gordon, S. C.;Zeuzem, S.
背景慢性丙型肝炎病毒（HCV）感染且在使用含有直接作用抗病毒药物（DAA）的方案治疗后没有持续病毒学应答的患者的再治疗选择有限。方法我们进行了两项3期试验，涉及先前接受过含有DAA的方案治疗的患者。在 POLARIS-1 中，先前接受过含有 NS5A 抑制剂治疗方案的 HCV 基因型 1 感染患者以 1:1 的比例随机分配接受核苷酸聚合酶抑制剂索磷布韦、NS5A 抑制剂维帕他韦和蛋白酶抑制剂沃西拉瑞韦（150 名患者）或匹配的安慰剂（150 名患者），每天一次，持续 12 周。感染其他基因型 HCV 的患者（114 例）被纳入索磷布韦-维帕他韦-沃西拉瑞韦组。在 POLARIS-4 中，先前接受过 DAA 方案但未接受过 NS5A 抑制剂的 HCV 基因型 1、2 或 3 感染患者以 1:1 的比例随机分配接受索磷布韦-维帕他韦-沃西拉瑞韦（163 名患者）或索磷布韦-维帕他韦（151 名患者）治疗，疗程为 12 周。另外 19 名 HCV 基因 4 型感染患者被纳入索磷布韦-维帕他韦-沃西拉瑞韦组。 结果 在三个积极治疗组中，46% 的患者出现代偿性肝硬化。在 POLARIS-1 中，索磷布韦-维帕他韦-沃西拉瑞韦的持续病毒学应答率为 96%，而安慰剂组的持续病毒学应答率为 0%。在 POLARIS-4 中，索磷布韦-维帕他韦-沃西拉瑞韦的缓解率为 98%，索磷布韦-维帕他韦的缓解率为 90%。最常见的不良事件是头痛、疲劳、腹泻和恶心。在这两项试验的积极治疗组中，由于不良事件而停止治疗的患者百分比为 1% 或更低。结论：服用 12 周的阿非布韦-维帕他韦-沃西拉瑞韦，在先前 DAA 方案治疗失败的 HCV 基因型患者中，持续病毒学应答率较高。 （由吉利德科学公司资助；POLARIS-1 和 POLARIS-4 ClinicalTrials.gov 编号：NCT02607735 和 NCT02639247。）
BACKGROUNDPatients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options.METHODSWe conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir- velpatasvir-voxilaprevir (163 patients) or sofosbuvir-velpatasvir (151 patients) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group.RESULTSIn the three active-treatment groups, 46% of the patients had compensated cirrhosis. In POLARIS-1, the rate of sustained virologic response was 96% with sofosbuvir-velpatasvir-voxilaprevir, as compared with 0% with placebo. In POLARIS-4, the rate of response was 98% with sofosbuvir-velpatasvir-voxilaprevir and 90% with sofosbuvir-velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea. In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower.CONCLUSIONSSofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed. (Funded by Gilead Sciences; POLARIS-1 and POLARIS-4 ClinicalTrials.gov numbers, NCT02607735 and NCT02639247.)