12周simeprevir联合聚乙二醇干扰素/利巴韦林（PR）方案治疗初治丙型肝炎病毒（HCV）基因4型（GT4）感染且有轻度至中度纤维化并表现出早期治疗病毒学应答患者的疗效
Efficacy of a 12-Week Simeprevir Plus Peginterferon/Ribavirin (PR) Regimen in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection and Mild-To-Moderate Fibrosis Displaying Early On-Treatment Virologic Response.
作者信息
Asselah Tarik, Moreno Christophe, Sarrazin Christoph, Gschwantler Michael, Foster Graham R, Craxí Antonio, Buggisch Peter, Sanai Faisal, Bicer Ceyhun, Lenz Oliver, Van Dooren Gino, Nalpas Catherine, Lonjon-Domanec Isabelle, Schlag Michael, Buti Maria
机构信息
Hepatology Department, Beaujon Hospital, University of Paris, Paris, France.
CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
出版信息
PLoS One. 2017 Jan 5;12(1):e0168713. doi: 10.1371/journal.pone.0168713. eCollection 2017.
BACKGROUND
HCV GT4 accounts for up to 20% of HCV infections worldwide. Simeprevir, given for 12 weeks as part of a 24- or 48-week combination regimen with PR is approved for the treatment of chronic HCV GT4 infection. Primary study objectives were assessment of efficacy and safety of simeprevir plus PR in treatment-naïve patients with HCV GT4 treated for 12 weeks. Primary efficacy outcome was sustained virologic response 12 weeks post-treatment (SVR12). Additional objectives included investigation of potential associations of rapid virologic response and baseline factors with SVR12.
METHODS
This multicentre, open-label, single-arm study (NCT01846832) evaluated efficacy and safety of simeprevir plus PR in 67 patients with HCV GT4 infection. Patients were treatment-naïve, aged 18-70 years with METAVIR F0-F2 fibrosis. Patients with early virologic response (HCV RNA <25 IU/mL [detectable/undetectable in IL28B CC patients or undetectable in IL28B CT/TT patients] at Week 2 and undetectable at Weeks 4 and 8) were eligible to stop all treatment at the end of Week 12, otherwise PR therapy was continued to Week 24.
RESULTS
Of 67 patients treated, 34 (51%) qualified for 12-week treatment including all but one patient with IL28B CC genotype (14/15). All patients in the 12-week group had undetectable HCV RNA at end of treatment, and 97% (33/34) achieved SVR12. No new safety signals with simeprevir plus PR were identified. The proportion of patients experiencing Grade 3-4 adverse events was lower in the 12-week group than in the 24-week group.
CONCLUSIONS
Our findings on simeprevir plus PR therapy shortened to 12 weeks in patients with HCV GT4 infection with favourable baseline characteristics and displaying early on-treatment virologic response are encouraging. No new safety signals were associated with simeprevir plus PR in this study.
TRIAL REGISTRATION
NCT01846832.
背景
丙型肝炎病毒基因4型（HCV GT4）感染在全球范围内占丙型肝炎病毒感染的20%。西米普明作为与聚乙二醇干扰素联合使用的24周或48周联合治疗方案的一部分，给药12周，已被批准用于治疗慢性HCV GT4感染。主要研究目标是评估西米普明联合聚乙二醇干扰素对初治HCV GT4患者治疗12周的疗效和安全性。主要疗效指标是治疗后12周持续病毒学应答（SVR12）。其他目标包括研究快速病毒学应答和基线因素与SVR12之间的潜在关联。
方法
这项多中心、开放标签、单臂研究（NCT01846832）评估了西米普明联合聚乙二醇干扰素对67例HCV GT4感染患者的疗效和安全性。患者为初治患者，年龄在18至70岁之间，METAVIR F0 - F2纤维化。早期病毒学应答（第2周时HCV RNA <25 IU/mL [IL28B CC基因型患者中可检测/不可检测，或IL28B CT/TT基因型患者中不可检测]，第4周和第8周时不可检测）的患者有资格在第12周结束时停止所有治疗，否则聚乙二醇干扰素治疗持续至第24周。
结果
在接受治疗的67例患者中，34例（51%）符合12周治疗标准，其中除1例IL28B CC基因型患者外（14/15）。12周治疗组的所有患者在治疗结束时HCV RNA均不可检测，97%（33/34）实现了SVR12。未发现西米普明联合聚乙二醇干扰素的新安全信号。12周治疗组发生3 - 4级不良事件的患者比例低于24周治疗组。
结论
我们关于西米普明联合聚乙二醇干扰素治疗缩短至12周用于具有良好基线特征且显示早期治疗病毒学应答的HCV GT4感染患者的研究结果令人鼓舞。本研究中未发现西米普明联合聚乙二醇干扰素的新安全信号。
试验注册号
NCT01846832。
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