Boceprevir for untreated chronic HCV genotype 1 infection.
Boceprevir for untreated chronic HCV genotype 1 infection.
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DOI：
10.1056/nejmoa1010494
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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：
SPRINT-2 Investigators
中科院分区：
文献类型：
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作者：
Poordad F;McCone J Jr;Bacon BR;Bruno S;Manns MP;Sulkowski MS;Jacobson IM;Reddy KR;Goodman ZD;Boparai N;DiNubile MJ;Sniukiene V;Brass CA;Albrecht JK;Bronowicki JP;SPRINT-2 Investigators
聚乙二醇干扰素-利巴韦林治疗是目前慢性丙型肝炎病毒（HCV）感染的标准治疗。在HCV基因型1感染的病例中，持续病毒学应答率一直低于50%。Boceprevir是一种有效的口服HCV蛋白酶抑制剂，已在I期和II期研究中作为额外治疗进行了评估。我们进行了一项双盲研究，将既往未经治疗的HCV基因型1感染的成年人随机分为三组。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24周，第8周至第24周之间可检测到HCV RNA水平的患者接受安慰剂+聚乙二醇干扰素-利巴韦林治疗20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。非黑人患者和黑人患者分别入组和分析。共有938名非黑人和159名黑人患者接受了治疗。在非黑人队列中，第1组311例患者中有125例（40%）获得持续病毒学应答，第2组316例患者中有211例（67%）获得持续病毒学应答（P<0.001），第3组311例患者中有213例（68%）获得持续病毒学应答（P<0.001）。在黑人队列中，第1组52例患者中有12例（23%）、第2组52例患者中有22例（42%）（P = 0.04）和第3组55例患者中有29例（53%）（P = 0.004）实现了持续病毒学应答。在第2组中，共有44%的患者接受聚乙二醇干扰素-利巴韦林治疗28周。贫血导致13%的对照组和21%的boceprevir接受者剂量减少，分别有1%和2%的人停药。在聚乙二醇干扰素-利巴韦林标准治疗基础上加用博赛泼维，与单独标准治疗相比，显著增加了既往未经治疗的慢性HCV基因型1感染成人的持续病毒学应答率。24周和44周boceprevir的发生率相似。（由先灵葆雅[现为默克]资助; SPRINT-2 ClinicalTrials.gov编号，NCT 00705432。）
Peginterferon–ribavirin therapy is the current standard of care for chronic infection with hepatitis C virus (HCV). The rate of sustained virologic response has been below 50% in cases of HCV genotype 1 infection. Boceprevir, a potent oral HCV-protease inhibitor, has been evaluated as an additional treatment in phase 1 and phase 2 studies. We conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were randomly assigned to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the leadin period). Subsequently, group 1 (the control group) received placebo plus peginterferon–ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon–ribavirin for 24 weeks, and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon–ribavirin for an additional 20 weeks; and group 3 received boceprevir plus peginterferon–ribavirin for 44 weeks. Nonblack patients and black patients were enrolled and analyzed separately. A total of 938 nonblack and 159 black patients were treated. In the nonblack cohort, a sustained virologic response was achieved in 125 of the 311 patients (40%) in group 1, in 211 of the 316 patients (67%) in group 2 (P<0.001), and in 213 of the 311 patients (68%) in group 3 (P<0.001). In the black cohort, a sustained virologic response was achieved in 12 of the 52 patients (23%) in group 1, in 22 of the 52 patients (42%) in group 2 (P = 0.04), and in 29 of the 55 patients (53%) in group 3 (P = 0.004). In group 2, a total of 44% of patients received peginterferon–ribavirin for 28 weeks. Anemia led to dose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2%, respectively. The addition of boceprevir to standard therapy with peginterferon–ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection. The rates were similar with 24 weeks and 44 weeks of boceprevir. (Funded by Schering-Plough [now Merck]; SPRINT-2 ClinicalTrials.gov number, NCT00705432.)