SOF/VEL/VOX 联合或不联合利巴韦林治疗慢性丙型肝炎的随机对照试验。
A randomized-controlled trial of SOF/VEL/VOX with or without ribavirin for retreatment of chronic hepatitis C.
机构信息
Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt.
Gastroenterology and Hepatology Department, National Hepatology & Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt.
出版信息
J Hepatol. 2023 Aug;79(2):314-320. doi: 10.1016/j.jhep.2023.04.011. Epub 2023 Apr 23.
BACKGROUND & AIMS: The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended for the retreatment of patients with HCV infection in whom previous direct-acting antiviral (DAA) treatment failed. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis in a randomized-controlled trial.
METHODS
We randomly assigned 315 patients with DAA treatment failure from five Egyptian sites into two groups. Group A (n = 158) received SOF/VEL/VOX for 12 weeks, and group B (n = 157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (sustained virologic response 12 weeks after treatment end). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities.
RESULTS
Males comprised 53.9% of group A and 57.1% of group B (p = 0.58); mean ages were 51.8 and 47.3 years in group A and B, respectively. Seventeen patients in each group were lost to follow-up. SVR12 rates were 87.3% (138/158) by intention-to-treat analysis and 97.8% (138/141) by per-protocol analysis in group A; and 87.9% (138/157) and 98.5% (138/140), respectively, in group B (p = n.s. for intention-to-treat and per-protocol analyses). Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B, which required ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any AE (p = 0.002).
CONCLUSION
This randomized-controlled trial showed equal, high efficacy of both regimens for the retreatment of previous DAA failures, although ribavirin was associated with more AEs. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy. CLINCIALTRIALS.
GOV NUMBER
NCT04695769.
IMPACT AND IMPLICATIONS
HCV treatment guidelines recommend retreatment of direct-acting antiviral (DAA) treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether ribavirin exerts an additional/synergistic effect remains unclear. The present study confirmed that SOF/VEL/VOX without ribavirin is the best regimen for retreatment of DAA treatment failures, and thus will help guide clinicians caring for patients who are not cured with a first course of DAA therapy.
背景与目的
对于先前直接作用抗病毒（DAA）治疗失败的丙型肝炎病毒（HCV）感染患者，推荐使用索磷布韦、维帕他韦和沃西拉韦（SOF/VEL/VOX）进行补救治疗。然而，利巴韦林是否进一步提高 SOF/VEL/VOX 补救治疗的疗效尚不清楚。我们旨在通过一项随机对照试验来检验这一假设。
方法
我们从埃及的五个地点随机分配了 315 名 DAA 治疗失败的患者进入两组。组 A（n=158）接受 SOF/VEL/VOX 治疗 12 周，组 B（n=157）接受 SOF/VEL/VOX+基于体重的利巴韦林治疗 12 周。治疗结束 12 周后的持续病毒学应答（SVR12）定义为治疗效果。通过监测与治疗相关的不良事件（AE）和实验室异常来评估安全性和耐受性。
结果
组 A 中男性占 53.9%，组 B 中占 57.1%（p=0.58）；组 A 和组 B 的平均年龄分别为 51.8 岁和 47.3 岁。每组各有 17 名患者失访。意向治疗分析中，SVR12 率分别为 87.3%（138/158）和 97.8%（138/141），组 A；分别为 87.9%（138/157）和 98.5%（138/140），组 B（意向治疗和方案分析的 p 值均为 n.s.）。两种方案均耐受良好，组 B 中仅 1 例发生严重不良事件（贫血），需要停止使用利巴韦林。组 A 中 55 例 vs. 组 B 中 77 例患者发生任何 AE（p=0.002）。
结论
这项随机对照试验表明，两种方案治疗先前 DAA 失败的疗效均很高，尽管利巴韦林相关的 AE 更多。因此，SOF/VEL/VOX 单药治疗应是首选的补救治疗策略。
临床试验。
注册号
NCT04695769。
影响与意义
HCV 治疗指南推荐使用索磷布韦、维帕他韦和沃西拉韦（SOF/VEL/VOX）联合治疗，持续 12 周，治疗 DAA 治疗失败。然而，利巴韦林是否具有额外/协同作用仍不清楚。本研究证实，不使用利巴韦林的 SOF/VEL/VOX 是治疗 DAA 治疗失败的最佳方案，这将有助于指导治疗未能治愈的患者的临床医生。
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