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Optimal treatment with boceprevir for chronic HCV infection

机译:用boceprevir最佳治疗慢性HCV感染

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摘要

There are 160-170 million people with chronic hepatitis C virus (HCV) infection worldwide. The marketing of protease inhibitors (PIs) has been a milestone in the history of HCV therapy. In phase III studies, up to 75% of the patients achieved a sustained virological response (SVR) after triple therapy with pegylated-interferon (PEG-IFN)-α, ribavirin (RBV) and boceprevir (BOC). However, triple regimens are more expensive and associated with drug-drug interactions (DDIs) and more adverse events (AEs). According to results in 'real-world' settings, safety seems to be limited, in particular in patients with advanced liver disease. To optimize efficacy while minimizing AEs as well as costs, the optimal treatment strategy must be determined for BOC. Optimizing treatment is based on patient selection, the most efficient treatment design, management of side effects and the challenge of DDIs. Therapy-associated risks, treatment urgency and chances of SVR must all be considered for patient selection. In addition, certain differences between the two approved PIs may help identify the ideal candidates for each HCV PI. Optimal treatment design is based on the results of phase II and III studies, in which different approaches have been tested including 'lead-in' and response-guided strategies. Treatment regimens and stopping rules recommended by the FDA and EMA should normally be followed. Still, there are some cases in which more personalized strategies may be more promising. Management of side effects is a major challenge and plays a crucial role in ensuring safety and adherence.
机译:全球有160-1.7亿人患有慢性丙型肝炎病毒(HCV)感染。蛋白酶抑制剂(PIs)的销售已成为HCV治疗历史上的一个里程碑。在III期研究中,使用聚乙二醇化干扰素(PEG-IFN)-α,利巴韦林(RBV)和boceprevir(BOC)进行三联治疗后,多达75%的患者获得了持续的病毒学应答(SVR)。然而,三联疗法更昂贵并且与药物-药物相互作用(DDI)和更多的不良事件(AE)相关。根据“实际”环境中的结果,安全性似乎受到限制,特别是对于晚期肝病患者。为了在最小化AE和成本的同时优化功效,必须为BOC确定最佳治疗策略。优化治疗的基础是患者选择,最有效的治疗设计,副作用管理和DDI挑战。选择患者时,必须考虑与治疗相关的风险,治疗的紧迫性和SVR的机会。此外,两个批准的效绩指标之间的某些差异可能有助于确定每个HCV效绩指标的理想候选人。最佳治疗设计基于II和III期研究的结果,其中已经测试了包括“导入”和反应指导策略在内的各种方法。通常应遵循FDA和EMA建议的治疗方案和停止规则。尽管如此,在某些情况下,更多的个性化策略可能更有希望。副作用的管理是一项重大挑战,并且在确保安全性和依从性方面起着至关重要的作用。

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