Elbasvir 和 Grazoprevir 治疗 1b 型丙型肝炎病毒感染患者的安全性和有效性。
The safety and efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 1b infection.
机构信息
Goethe University Hospital, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
Service d'Hépatologie, Hôpital Saint-Antoine, Université Pierre and Marie Curie, Paris, France.
出版信息
J Gastroenterol. 2018 May;53(5):679-688. doi: 10.1007/s00535-018-1429-3. Epub 2018 Jan 17.
BACKGROUND
Genotype 1b (GT1b) is the most common subtype of the hepatitis C virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b infection from 30 countries who received elbasvir/grazoprevir for 12 weeks.
METHODS
This is a retrospective analysis of data from participants with chronic HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks. The primary end point of all studies was sustained virologic response 12 weeks after completion of therapy (SVR12, HCV RNA < 15 IU/ml).
RESULTS
SVR12 was 97.2% (1040/1070). Of the 30 participants who failed to attain SVR12, 15 relapsed and 15 had nonvirologic failure. Among participant subgroups, SVR12 was high in those with compensated cirrhosis (188/189, 99.5%), HIV co-infection (51/54, 94.4%), and baseline viral load > 800,000 IU/ml (705/728, 96.8%). Resistance-associated substitutions (RASs) at NS5A positions 28, 30, 31, or 93 were present in 21.6% of participants at baseline. SVR12 was 99.6% (820/823) in participants without baseline NS5A RASs and 94.7% (215/227) in those with baseline NS5A RASs. Serious adverse events occurred in 3.2% (34/1070) of participants, nine of which occurred after study medication was completed.
CONCLUSIONS
Elbasvir/grazoprevir for 12 weeks represents an effective treatment option for participants with HCV GT1b infection. SVR12 was high in all participant subgroups, including those with compensated cirrhosis, HIV co-infection, and high baseline viral load. CLINICALTRIALS.
GOV IDENTIFIERS
The trials discussed in this paper were registered with Clinicaltrial.gov as the following: NCT02092350 (C-SURFER), NCT02105662 (C-EDGE Co-Infection), NCT02105467 (C-EDGE treatment-naive), NCT02105701 (C-EDGE treatment-experienced), NCT01717326 (C-WORTHy), NCT02251990 (C-CORAL), NCT02105688 (C-EDGE COSTAR), NCT02252016 (C-EDGE IBLD), NCT02115321 (C-SALT), NCT02203149 (Japan phase 2/3 study), NCT02358044 (C-EDGE Head-2-Head).
背景
基因 1b（GT1b）是丙型肝炎病毒（HCV）最常见的亚型。我们对来自 30 个国家的 1070 名接受 Elbasvir/grazoprevir 治疗 12 周的 HCV GT1b 感染患者进行了综合分析。
方法
这是对 11 项 II/III 期临床试验中慢性 HCV GT1b 感染患者进行的数据的回顾性分析。所有患者均接受 Elbasvir 50mg 加 Grazoprevir 100mg 每日一次治疗 12 周。所有研究的主要终点均为治疗结束后 12 周持续病毒学应答（SVR12，HCV RNA < 15IU/ml）。
结果
SVR12 为 97.2%（1040/1070）。在 30 名未能达到 SVR12 的患者中，15 名复发，15 名发生非病毒学失败。在各亚组患者中，代偿性肝硬化（188/189，99.5%）、HIV 合并感染（51/54，94.4%）和基线病毒载量>800,000IU/ml（705/728，96.8%）患者的 SVR12 较高。基线时 NS5A 位置 28、30、31 或 93 处存在耐药相关替代（RAS）的患者占 21.6%。无基线 NS5A RAS 的患者 SVR12 为 99.6%（820/823），有基线 NS5A RAS 的患者为 94.7%（215/227）。1070 名患者中有 3.2%（34/1070）发生严重不良事件，其中 9 例发生在研究药物完成后。
结论
Elbasvir/grazoprevir 治疗 12 周是 HCV GT1b 感染患者的有效治疗选择。所有患者亚组的 SVR12 均较高，包括代偿性肝硬化、HIV 合并感染和高基线病毒载量患者。
临床试验.gov 注册号：本文讨论的试验在 Clinicaltrial.gov 上注册如下：NCT02092350（C-SURFER）、NCT02105662（C-EDGE Co-Infection）、NCT02105467（C-EDGE treatment-naive）、NCT02105701（C-EDGE treatment-experienced）、NCT01717326（C-WORTHy）、NCT02251990（C-CORAL）、NCT02105688（C-EDGE COSTAR）、NCT02252016（C-EDGE IBLD）、NCT02115321（C-SALT）、NCT02203149（日本 2/3 期研究）、NCT02358044（C-EDGE Head-2-Head）。
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