Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
Liver Int. 2017 Sep;37(9):1325-1333. doi: 10.1111/liv.13384. Epub 2017 Mar 17.
BACKGROUND & AIMS: It is important to investigate the treatment outcomes in patients excluded from clinical trials (CTR). The aims of this study were to evaluate the efficacy and safety of a 24-week daclatasvir (DCV) and asunaprevir (ASV) therapy for patients with chronic hepatitis C virus (HCV)-1b infection.
A total of 651 HCV-1b patients started dual oral therapy with DCV and ASV for 24 weeks in Toranomon Hospital, Tokyo. Among them, 276 patients met phase III CTR inclusion criteria. The sustained virological response (SVR) rate after treatment and the adverse events during therapy were compared between CTR-met (patients who met the inclusion criteria) and CTR-unmet (patients who did not meet the inclusion criteria) groups.
SVR12 was achieved in 87.0% (240/276) and 86.7% (325/375) in CTR-met and CTR-unmet patients respectively. SVR12 rate in simeprevir-experienced patients was 52.9% (9/17). SVR12 rate in patients without resistance-associated variant (RAV) of NS3 or NS5A loci was 93.7% (416/444). However, the SVR12 rates in patients with NS3-D168, NS5A-L31 and Y93 single RAV at baseline were 55.0% (11/20), 73.9% (17/23) and 65.6% (63/96) respectively. The safety profiles in both CTR-met and CTR-unmet patients were similar. The discontinuation rate as a result of alanine aminotransferase (ALT) elevation was only 2.9%. Seven (2.5%) patients in CTR-met group and 20 (5.3%) in CTR-unmet group discontinued therapy because of adverse events other than the ALT elevation.
Dual oral therapy with DCV and ASV in real-life settings was well tolerated with a similar safety profile and achieved similar SVR12 rates as that of CTR.
研究排除在临床试验（CTR）之外的患者的治疗结果非常重要。本研究旨在评估替拉那韦（DCV）和阿舒瑞韦（ASV）联合治疗 24 周治疗慢性丙型肝炎病毒（HCV）-1b 感染患者的疗效和安全性。
共有 651 例 HCV-1b 患者在东京 Toranomon 医院开始接受 DCV 和 ASV 的双口服治疗，为期 24 周。其中，276 例患者符合 III 期 CTR 纳入标准。比较治疗后持续病毒学应答（SVR）率和治疗期间的不良反应在符合 CTR（符合纳入标准的患者）和不符合 CTR（不符合纳入标准的患者）两组之间的差异。
符合 CTR 的患者的 SVR12 率为 87.0%（240/276），不符合 CTR 的患者的 SVR12 率为 86.7%（325/375）。simeprevir 治疗经验患者的 SVR12 率为 52.9%（9/17）。无 NS3 或 NS5A 基因座耐药相关变异（RAV）的患者的 SVR12 率为 93.7%（444/444）。然而，基线时 NS3-D168、NS5A-L31 和 Y93 单个 RAV 的患者的 SVR12 率分别为 55.0%（11/20）、73.9%（17/23）和 65.6%（63/96）。符合 CTR 和不符合 CTR 的患者的安全性特征相似。由于丙氨酸氨基转移酶（ALT）升高而停药的发生率仅为 2.9%。符合 CTR 组中有 7 例（2.5%）患者和不符合 CTR 组中有 20 例（5.3%）患者因 ALT 升高以外的不良反应而停止治疗。
在真实环境中，DCV 和 ASV 的双口服治疗耐受性良好，安全性相似，SVR12 率与 CTR 相似。
