The Texas Liver Institute, University of Texas Health, San Antonio, Texas, USA.
Private Practice, Bakersfield, California, USA.
Liver Int. 2022 Jun;42(6):1278-1286. doi: 10.1111/liv.15211. Epub 2022 Mar 14.
This study aimed to determine durability of sustained virologic response (SVR) in hepatitis C virus-infected participants treated with glecaprevir- and/or pibrentasvir-containing regimens.
M13-576, a rollover study, evaluated the durability of SVR in a follow-up period of approximately 3 years after hepatitis C virus genotype 1-6-infected participants received a glecaprevir- and/or pibrentasvir-containing regimen in previous phase 2/3 clinical trials. The primary efficacy endpoint was the percentage of participants maintaining SVR and the percentage of participants experiencing relapse or reinfections. Resistance-associated substitutions and safety outcomes related to liver progression were also assessed.
Of 384 participants enroled, 377 participants were included in the as-observed population and 287 participants completed the study. In prior studies, 99.7% (376/377) of participants achieved SVR12; of those, an observed 99.5% (374/376) and 100% (286/286) completing the study, maintained SVR. After non-responder imputation of missing data, 286/376 participants (76%) maintained SVR. The participant previously not achieving SVR was a treatment-experienced male with compensated cirrhosis who had NS3 and NS5A substitutions at enrolment, which remained detectable for 12 months. Of the two participants not maintaining SVR, one was re-infected and one experienced late relapse at post-treatment week 60. Five participants (all with a fibrosis stage ≥F3) had hepatocellular carcinoma. No events were deemed related to glecaprevir/pibrentasvir.
Glecaprevir/pibrentasvir demonstrated long-term durability of efficacy after SVR12 was achieved. Hepatic-related decompensation events were not seen. Owing to low incidence of virologic failure, conclusions were not drawn on persistence of resistance-associated substitutions.
本研究旨在确定接受格卡瑞韦/哌仑他韦联合治疗的丙型肝炎病毒感染者持续病毒学应答（SVR）的持久性。
M13-576 是一项滚动研究，评估了丙型肝炎病毒基因型 1-6 感染者在先前的 2/3 期临床试验中接受格卡瑞韦/哌仑他韦联合治疗后，约 3 年的随访期间 SVR 的持久性。主要疗效终点为维持 SVR 的参与者比例和发生复发或再感染的参与者比例。还评估了与肝脏进展相关的耐药相关替换和安全性结局。
在纳入的 384 名参与者中，377 名参与者进入了观察人群，287 名参与者完成了研究。在先前的研究中，99.7%（376/377）的参与者达到了 SVR12；其中，观察到 99.5%（374/376）和 100%（286/286）完成研究的参与者维持了 SVR。在对缺失数据进行未应答者推断后，286/376 名参与者（76%）维持了 SVR。未达到 SVR 的参与者是一名有代偿性肝硬化的治疗经验丰富的男性，他在入组时就有 NS3 和 NS5A 替换，这些替换在 12 个月内仍可检测到。在未维持 SVR 的两名参与者中，一名是再感染，另一名是在治疗后第 60 周发生晚期复发。五名参与者（均有纤维化分期≥F3）患有肝细胞癌。没有事件被认为与格卡瑞韦/哌仑他韦有关。
格卡瑞韦/哌仑他韦在达到 SVR12 后显示出长期疗效持久性。没有观察到与肝脏相关的失代偿事件。由于病毒学失败的发生率较低，因此没有对耐药相关替换的持久性得出结论。
