INSERM U1052-CNRS 5286, Cancer Research Center of Lyon (CRCL) and Hepatology Department, Lyon, France.
CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
Virol J. 2018 Jan 30;15(1):26. doi: 10.1186/s12985-018-0936-4.
Simeprevir is approved with pegylated interferon and ribavirin (PR) for chronic hepatitis C virus (HCV) genotype (GT) 1 and GT4 infection in the USA and the European Union.
This 3-year follow-up study assessed the durability of sustained virologic response (SVR) (undetectable HCV RNA 12 or 24 weeks after treatment end), and evaluated the persistence of treatment-emergent NS3/4A protease inhibitor resistance in patients not achieving SVR following treatment with simeprevir plus PR in the parent study. The maintenance of SVR after the last post-therapy follow-up visit of the parent study (LPVPS) was assessed using HCV RNA measurements. The persistence of treatment-emergent NS3 amino acid substitutions in patients with no SVR at LPVPS was assessed using population sequencing. No study medications were administered.
Overall, 249 patients were enrolled (200 with SVR at LPVPS; 49 with no SVR at LPVPS); 40 patients discontinued prematurely (18 with SVR; 22 with no SVR). All 200 enrolled patients who achieved SVR in the parent study maintained SVR until the last available visit in this study (median follow-up time: 35.8 months). The treatment-emergent NS3 amino acid substitutions detected at time of failure in the parent study in 43/49 enrolled patients were no longer detected in 37/43 (86.0%) at the end of this study (median follow-up time: 179.9 weeks [41.3 months]).
This 3-year follow-up study provides evidence for the long-term durability of SVR (100%) after successful treatment with simeprevir plus PR. Treatment-emergent NS3 amino acid substitutions became undetectable in the majority of patients.
NCT01349465; ClinicalTrials.gov .
simeprevir 与聚乙二醇干扰素和利巴韦林（PR）联合用于治疗美国和欧盟的慢性丙型肝炎病毒（HCV）基因型（GT）1 和 GT4 感染。
这项为期 3 年的随访研究评估了持续病毒学应答（SVR）（治疗结束后 12 或 24 周时 HCV RNA 不可检测）的持久性，并评估了在主要研究中接受simeprevir 加 PR 治疗后未达到 SVR 的患者中治疗后出现的 NS3/4A 蛋白酶抑制剂耐药性的持续存在。使用 HCV RNA 测量评估从主要研究的最后一次治疗后随访（LPVPS）后的 SVR 维持情况。使用群体测序评估在 LPVPS 时无 SVR 的患者中治疗后出现的 NS3 氨基酸取代的持续存在情况。未给予研究药物。
总体而言，共纳入 249 例患者（LPVPS 时 200 例 SVR；LPVPS 时 49 例无 SVR）；40 例患者提前停药（18 例 SVR；22 例无 SVR）。主要研究中所有 200 例达到 SVR 的入组患者在本研究的最后一次可随访时均维持 SVR（中位随访时间：35.8 个月）。在主要研究中，49 例入组患者中有 43 例在失败时检测到的治疗后出现的 NS3 氨基酸取代在本研究结束时（中位随访时间：179.9 周[41.3 个月]）已不再检测到。
这项为期 3 年的随访研究为 simeprevir 联合 PR 成功治疗后的 SVR（100%）的长期持久性提供了证据。治疗后出现的 NS3 氨基酸取代在大多数患者中变得不可检测。
NCT01349465；ClinicalTrials.gov 。
