Pharmacy Service, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468, USA.
Clin Ther. 2012 Oct;34(10):2021-38. doi: 10.1016/j.clinthera.2012.08.009. Epub 2012 Sep 11.
Boceprevir is a protease inhibitor indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in combination with peginterferon and ribavirin for treatment-naive patients and those who previously failed to improve with interferon and ribavirin treatment.
This article provides an overview of the mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of boceprevir.
Relevant information was identified through a search of PubMed (1990-July 2012), EMBASE (1990-July 2012), International Pharmaceutical Abstracts (1970-July 2012), and Google Scholar using the key words boceprevir, SCH 503034, non-structural protein 3 (NS3) serine protease inhibitor, and direct-acting antiviral agent (DAA). Additional information was obtained from the US Food and Drug Administration's Web site, review of the reference lists of identified articles, and posters and abstracts from scientific meetings.
Clinical efficacy of boceprevir was assessed in 2 Phase III trials, Serine Protease Inhibitor Therapy-2 (SPRINT-2) for treatment-naive patients and Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) for treatment-experienced patients. In SPRINT-2, patients were randomized to receive peginterferon + ribavirin (PR) or peginterferon + ribavirin + boceprevir (PRB); duration of boceprevir therapy varied from 24, 32, to 44 weeks on the basis of HCV RNA results. The primary endpoint was achievement of sustained virologic response (SVR; lower limit of detection, 9.3 IU/mL). The addition of boceprevir was shown to be superior, with overall SVR rates ranging from 63% to 66% compared with 38% with PR (P < 0.001). Results of SVR in SPRINT-2 were also reorganized to monitor SVRs in black and non-black patients. Treatment-experienced patients were assessed in RESPOND-2; however, null responders were excluded. Patients were again randomized to PR or PRB; duration of boceprevir therapy varied from 32 to 44 weeks on the basis of HCV RNA results. SVR was significantly higher in patients receiving boceprevir (59%-66% vs 21% with PR; P < 0.001). This benefit was seen in both previous nonresponders (SVR, 40%-52% vs 7% with PR), as well as previous relapsers (SVR, 69%-75% vs 29% with PR). Importantly, SVR could be attained with a shortened course of therapy in almost one half of all treated patients in SPRINT-2 (44%) and RESPOND-2 (46%).
Boceprevir was well tolerated in clinical trials and a welcomed addition to our HCV armamentarium.
博赛泼维是一种蛋白酶抑制剂，适用于治疗慢性丙型肝炎病毒（HCV）基因型 1 感染，与聚乙二醇干扰素和利巴韦林联合用于初治患者和那些先前因干扰素和利巴韦林治疗而未改善的患者。
本文概述了博赛泼维的作用机制、药效学和药代动力学特性、临床疗效和耐受性。
通过在 PubMed（1990 年-2012 年 7 月）、EMBASE（1990 年-2012 年 7 月）、国际药学文摘（1970 年-2012 年 7 月）和 Google Scholar 上搜索 boceprevir、SCH 503034、非结构蛋白 3（NS3）丝氨酸蛋白酶抑制剂和直接作用抗病毒药（DAA）等关键词，查找相关信息。还从美国食品和药物管理局的网站、已确定文章的参考文献列表、科学会议的海报和摘要中获取了其他信息。
在两项 III 期临床试验中评估了博赛泼维的临床疗效，即初治患者的 Serine Protease Inhibitor Therapy-2（SPRINT-2）和治疗经验患者的 HCV Serine Protease Inhibitor Boceprevir 和 PegIntron/Rebetol 2（RESPOND-2）。在 SPRINT-2 中，患者被随机分配接受聚乙二醇干扰素+利巴韦林（PR）或聚乙二醇干扰素+利巴韦林+博赛泼维（PRB）；根据 HCV RNA 结果，博赛泼维治疗的持续时间从 24、32 到 44 周不等。主要终点是获得持续病毒学应答（SVR；检测下限为 9.3 IU/mL）。加用博赛泼维的疗效优于 PR，总 SVR 率为 63%至 66%，而 PR 为 38%（P < 0.001）。SPRINT-2 中的 SVR 结果也进行了重新组织，以监测黑人患者和非黑人患者的 SVR。在 RESPOND-2 中评估了治疗经验患者；但是，排除了无应答者。患者再次被随机分配接受 PR 或 PRB；根据 HCV RNA 结果，博赛泼维治疗的持续时间从 32 到 44 周不等。接受博赛泼维治疗的患者 SVR 显著高于 PR（59%-66% vs PR 21%；P < 0.001）。这种益处见于既往无应答者（SVR，40%-52% vs PR 7%）和既往复发者（SVR，69%-75% vs PR 29%）。重要的是，SPRINT-2（44%）和 RESPOND-2（46%）中近一半的所有接受治疗的患者都可以通过缩短疗程来获得 SVR。
博赛泼维在临床试验中耐受性良好，是我们 HCV 治疗武器库中的一个受欢迎的补充。
