Boceprevir for previously treated chronic HCV genotype 1 infection.
Boceprevir for previously treated chronic HCV genotype 1 infection.
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DOI：
10.1056/nejmoa1009482
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发表时间：
2011-03-31
期刊：
影响因子：
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通讯作者：
HCV RESPOND-2 Investigators
中科院分区：
文献类型：
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作者：
Bacon BR;Gordon SC;Lawitz E;Marcellin P;Vierling JM;Zeuzem S;Poordad F;Goodman ZD;Sings HL;Boparai N;Burroughs M;Brass CA;Albrecht JK;Esteban R;HCV RESPOND-2 Investigators
对于对聚乙二醇干扰素-利巴韦林治疗无持续应答的慢性丙型肝炎病毒（HCV）基因型1型感染患者，再次治疗后的结局不理想。Boceprevir是一种蛋白酶抑制剂，与HCV非结构3（NS 3）活性位点结合，已被建议作为一种额外的治疗方法。为了评估博赛泼维和聚乙二醇干扰素-利巴韦林联合治疗慢性HCV基因型1型感染患者的效果，我们将患者随机分配（1：2：2比例）到三组中的一组。在所有三组中，聚乙二醇干扰素α-2b和利巴韦林给药4周（导入期）。随后，第1组（对照组）接受安慰剂+聚乙二醇干扰素-利巴韦林治疗44周;第2组接受博赛泼维+聚乙二醇干扰素-利巴韦林治疗32周，第8周时HCV RNA水平可检测的患者接受安慰剂+聚乙二醇干扰素-利巴韦林治疗12周;第3组接受博赛泼维+聚乙二醇干扰素-利巴韦林治疗44周。共有403名患者接受了治疗。两个博赛泼维组的持续病毒学应答率（第2组，59%;第3组，66%）显著高于对照组（21%，P<0.001）。在第8周HCV RNA水平检测不到的患者中，三联治疗32周后的持续病毒学应答率为86%，三联治疗44周后为88%。在治疗第4周HCV RNA水平下降小于1 log 10 IU/ml的102例患者中，第1、2和3组的持续病毒学应答率分别为0%、33%和34%。博赛泼韦组的贫血明显比对照组更常见，41%至46%的博赛泼韦治疗患者和21%的对照组给予促红细胞生成素。在既往接受过治疗的慢性HCV基因型1感染患者中，与单独使用聚乙二醇干扰素-利巴韦林相比，在聚乙二醇干扰素-利巴韦林的基础上添加博赛泼维可显著提高持续病毒学应答率。
In patients with chronic infection with hepatitis C virus (HCV) genotype 1 who do not have a sustained response to therapy with peginterferon–ribavirin, outcomes after retreatment are suboptimal. Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3 (NS3) active site, has been suggested as an additional treatment. To assess the effect of the combination of boceprevir and peginterferon–ribavirin for retreatment of patients with chronic HCV genotype 1 infection, we randomly assigned patients (in a 1:2:2 ratio) to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (control group) received placebo plus peginterferon–ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon–ribavirin for 32 weeks, and patients with a detectable HCV RNA level at week 8 received placebo plus peginterferon–ribavirin for an additional 12 weeks; and group 3 received boceprevir plus peginterferon–ribavirin for 44 weeks. A total of 403 patients were treated. The rate of sustained virologic response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%, P<0.001). Among patients with an undetectable HCV RNA level at week 8, the rate of sustained virologic response was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients with a decrease in the HCV RNA level of less than 1 log10 IU per milliliter at treatment week 4, the rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively. Anemia was significantly more common in the boceprevir groups than in the control group, and erythropoietin was administered in 41 to 46% of boceprevir-treated patients and 21% of controls. The addition of boceprevir to peginterferon–ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon–ribavirin alone.