Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection
Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection
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DOI：
10.1056/nejmc1307641
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发表时间：
2013-05-16
影响因子：
158.5
通讯作者：
Gane, Edward J.
中科院分区：
文献类型：
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作者：
Lawitz, Eric;Mangia, Alessandra;Gane, Edward J.
致编辑：(1)Lawitz等人在两期3期研究中发表的关于在先前未经治疗的慢性丙型肝炎病毒(丙型肝炎病毒)感染患者中使用索索布韦的文章(1)。结论：在中微子试验中，加入索索布韦对感染1、4、5或6型丙型肝炎病毒的患者有效。然而，在3型感染患者中，接受索布韦和利巴韦林治疗的患者的应答率低于2型感染患者(裂变试验)。尽管对于后一项试验，作者提供了有无肝硬变的数据...背景在2期试验中，核苷酸聚合酶抑制剂索莫布韦对既往未经治疗的慢性丙型肝炎病毒(丙型肝炎病毒)1、2或3型感染患者有效。在一项单组开放研究中，我们对327名丙型肝炎病毒基因1、4、5或6(其中98%为基因1或4)的患者进行了为期12周的索莫布韦加聚乙二醇干扰素α-2a和利巴韦林治疗。在一项非劣效性试验中，499名丙型肝炎病毒基因2或3感染的患者被随机分配到索布韦加利巴韦林治疗12周或聚乙二醇干扰素α-2a加利巴韦林治疗24周。在这两项研究中，主要的终点是治疗结束后12周的持续病毒学应答。结果在单组研究中，90%的患者报告了持续的病毒学应答(95%的可信区间，87到93)。在非劣效性试验中，索非司布韦-利巴韦林组和聚乙二醇干扰素-利巴韦林组均有67%的患者持续有效。在3型感染者中，索布韦-利巴韦林组的有效率低于2型感染者(56%比97%)。与聚乙二醇干扰素相比，索索布韦的不良反应(包括乏力、头痛、恶心和中性粒细胞减少)较少。结论在索索布韦联合聚乙二醇干扰素-利巴韦林的单组研究中，以1或4型丙型肝炎病毒感染为主的患者在12周时的持续病毒学应答率为90%。在一项非劣效性试验中，接受索布韦或聚乙二醇干扰素与利巴韦林联合治疗的2型或3型感染者的应答率几乎相同(67%)。与聚乙二醇干扰素相比，索索布韦的不良反应发生率较低。(由Gilead Sciences提供资金；裂变和中微子诊所试验编号分别为NCT01497366和NCT01641640。)
To the Editor: In their article on the use of sofosbuvir in previously untreated patients with chronic hepatitis C virus (HCV) infection in two phase 3 studies (May 16 issue),(1) Lawitz et al. conclude that the addition of sofosbuvir was effective in patients who were infected with HCV genotype 1, 4, 5, or 6 (NEUTRINO trial). However, response rates in the group that received sofosbuvir and ribavirin were lower among patients with genotype 3 infection than among those with genotype 2 infection (FISSION trial). Although for the latter trial, the authors provide data on the presence or absence of cirrhosis, ...BACKGROUNDIn phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection.METHODSWe conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy.RESULTSIn the single-group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67% of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group. Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56% vs. 97%). Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon.CONCLUSIONSIn a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67%). Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640, respectively.)