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开发中的慢性丙型肝炎药物:前景广阔。

Drugs in development for chronic hepatitis C: a promising future.

机构信息

Division of Gastroenterology/Hepatology and Liver Disease Center, The Scripps Translational Science Institute and The Scripps Research Institute, Scripps Clinic, La Jolla, CA 92037, USA.

出版信息

Expert Opin Biol Ther. 2011 Dec;11(12):1611-22. doi: 10.1517/14712598.2011.627851. Epub 2011 Oct 13.

Abstract

INTRODUCTION

The approval of the first direct-acting antiviral (DAA) drugs for treatment of HCV in 2011 has lead to improved sustained viral response rates of up to 79% in treatment-naïve or relapse genotype 1 patients.

AREAS COVERED

Clinical trial data, the clinical skills required for the use of DAA drugs, the use of genetic tests and HCV RNA assays, new small molecules, resistance-associated variants, combinations of two or more DAAs, treatment of special populations, and future directions. The results of the pivotal Phase III trials with telaprevir and boceprevir, including the efficacy, safety and tolerability, drug-drug interactions and management of the most common side-effects. Resistance-associated variant data and treatment strategies implemented to minimize the development of resistance with these first-generation protease inhibitors.

EXPERT OPINION

Combination therapies of protease inhibitors with nucleoside or non-nucleoside polymerase inhibitors, non-structural protein 5A (NS5A) inhibitors and cyclophylin inhibitors are currently underway in regimens that use pegylated interferon and ribavirin or are interferon-free. The explosion of new drug development will probably move the field forward and offer both improved efficacy and tolerability to patients with hepatitis C infections. The use of these drugs ushers in a new era for the treatment of HCV but must be done with care and caution.

摘要

简介

2011 年首个直接作用抗病毒药物(DAA)获批用于 HCV 治疗,使初治或复发基因型 1 患者的持续病毒学应答率提高至 79%。

涵盖领域

临床试验数据、使用 DAA 药物所需的临床技能、基因检测和 HCV RNA 检测、新型小分子药物、耐药相关变异体、两种或更多 DAA 的联合应用、特殊人群的治疗以及未来方向。替拉瑞韦和博赛匹韦关键性 III 期临床试验的结果,包括疗效、安全性和耐受性、药物相互作用以及最常见副作用的管理。与第一代蛋白酶抑制剂相关的耐药相关变异体数据和治疗策略,旨在最大限度减少耐药性的产生。

专家意见

目前正在进行蛋白酶抑制剂与核苷(酸)或非核苷(酸)聚合酶抑制剂、非结构蛋白 5A(NS5A)抑制剂和环孢素抑制剂联合治疗方案的研究,这些方案既使用聚乙二醇干扰素和利巴韦林,也有不使用干扰素的方案。新药研发的爆发可能会推动该领域的发展,为 HCV 感染患者提供更好的疗效和耐受性。这些药物的使用为 HCV 治疗带来了新时代,但必须谨慎使用。

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