西米普明联合索磷布韦（12周和8周疗程）用于无肝硬化的丙型肝炎病毒1型感染患者：OPTIMIST-1，一项3期随机研究。
Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study.
作者信息
Kwo Paul, Gitlin Norman, Nahass Ronald, Bernstein David, Etzkorn Kyle, Rojter Sergio, Schiff Eugene, Davis Mitchell, Ruane Peter, Younes Ziad, Kalmeijer Ronald, Sinha Rekha, Peeters Monika, Lenz Oliver, Fevery Bart, De La Rosa Guy, Scott Jane, Witek James
机构信息
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, IN.
Atlanta Gastroenterology Associates, Atlanta, GA.
出版信息
Hepatology. 2016 Aug;64(2):370-80. doi: 10.1002/hep.28467. Epub 2016 Mar 22.
UNLABELLED
Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naive and prior null-responder HCV genotype (GT) 1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12 or 24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naive and treatment-experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. Enrolled were 310 patients, who were randomized and received treatment (n = 155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97% [150/155; 95% confidence interval 94%-100%]) was superior to the historical control (87%). SVR12 with simeprevir+sofosbuvir for 8 weeks (83% [128/155; 95% confidence interval 76-89%]) was not superior to the historical control (83%). The most frequent adverse events were nausea, headache, and fatigue (12-week arm: 15% [23/155], 14% [22/155], and 12% [19/155]; 8-week arm: 9% [14/155], 17% [26/155], and 15% [23/155], respectively). No patients discontinued treatment due to an adverse event. One (1%, 12-week arm) and three (2%, 8-week arm) patients experienced a serious adverse event (all unrelated to study treatment).
CONCLUSION
Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1-infected patients without cirrhosis, including those with Q80K. (Hepatology 2016;64:370-380).
未标注
有效的抗病毒治疗对于丙型肝炎病毒（HCV）感染患者实现持续病毒学应答（SVR）至关重要。2期COSMOS研究报告称，在接受simeprevir+索磷布韦±利巴韦林治疗12周或24周的初治和既往无应答的HCV基因1型（GT1）感染患者中，SVR率较高。OPTIMIST-1（NCT02114177）是一项多中心、随机、开放标签研究，评估simeprevir+索磷布韦治疗12周和8周在无肝硬化的HCV GT1感染初治和经治患者中的疗效和安全性。患者被随机分配（1:1；按HCV GT/亚型、NS3 Q80K多态性的有无[GT1b、有Q80K的GT1a、无Q80K的GT1a]、既往HCV治疗史和IL28B GT[CC、非CC]分层）接受每日一次150mg simeprevir+每日一次400mg索磷布韦治疗12周或8周。主要疗效终点是治疗结束后12周的SVR率（SVR12）。评估了12周和8周的simeprevir+索磷布韦与综合历史对照SVR率相比在SVR12方面的优越性。共纳入310例患者，他们被随机分组并接受治疗（每组155例）。12周的simeprevir+索磷布韦治疗的SVR12（97%[150/155；95%置信区间94%-100%]）优于历史对照（87%）。8周的simeprevir+索磷布韦治疗的SVR12（83%[128/155；95%置信区间76-89%]）不优于历史对照（83%）。最常见的不良事件是恶心、头痛和疲劳（12周组：15%[23/155]、14%[22/155]和12%[19/155]；8周组：分别为9%[14/155]、17%[26/155]和15%[23/155]）。没有患者因不良事件而停药。1例（1%，12周组）和3例（2%，8周组）患者发生严重不良事件（均与研究治疗无关）。
结论
12周的simeprevir+索磷布韦治疗无肝硬化包括有Q80K的HCV GT1感染患者非常有效。（《肝脏病学》2016年；64:370-380）
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