El Raziky M, Gamil M, Ashour M K, Sameea E A, Doss W, Hamada Y, Van Dooren G, DeMasi R, Keim S, Lonjon-Domanec I, Hammad R, Hashim M S, Hassany M, Waked I
Faculty of Medicine, Cairo University, Cairo, Egypt.
Janssen Research & Development, Beerse, Belgium.
J Viral Hepat. 2017 Feb;24(2):102-110. doi: 10.1111/jvh.12625. Epub 2016 Oct 27.
The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus (HCV) genotype 4-infected patients with METAVIR F0-F4 fibrosis. Sixty-three patients (33 treatment-naïve and 30 peg-interferon/ribavirin (Peg-IFN/RBV)-experienced) enrolled in a partly randomized, open-label, multicentre, phase IIa study. Patients with F0-F3 fibrosis were randomized (1:1) into two groups (A1 and A2), stratified according to treatment experience and METAVIR score, to receive either eight weeks (Group A1, n=20) or 12 weeks (Group A2, n=20) of treatment. Patients with compensated cirrhosis (METAVIR F4) received 12 weeks of treatment (Group B, n=23). Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Safety and tolerability were assessed throughout. Overall, 92% (95% CI: 82-97) of patients achieved SVR12; 75% (15/20) in Group A1 and 100% in groups A2 and B. Patients who did not achieve SVR12 (n=5) experienced viral relapse during the first 32 days following treatment and were all prior Peg-IFN/RBV null responders. The most commonly reported treatment-emergent adverse events (TEAEs) were asymptomatic lipase increase (14%), pruritus (14%), headache (13%) and hyperbilirubinaemia (11%). No patients discontinued due to TEAEs. In conclusion, simeprevir plus sofosbuvir for 12 weeks achieved a 100% SVR rate in HCV genotype 4-infected patients with or without compensated cirrhosis (ClinicalTrials.gov: NCT02278419). The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight- and 12-week regimens.
OSIRIS研究调查了西米普明联合索磷布韦治疗丙型肝炎病毒（HCV）基因4型感染、METAVIR F0-F4纤维化患者8周或12周的疗效和安全性。63例患者（33例初治患者和30例聚乙二醇干扰素/利巴韦林（Peg-IFN/RBV）经治患者）参与了一项部分随机、开放标签、多中心IIa期研究。F0-F3纤维化患者按治疗经验和METAVIR评分分层，随机（1:1）分为两组（A1组和A2组），分别接受8周（A1组，n=20）或12周（A2组，n=20）治疗。代偿期肝硬化（METAVIR F4）患者接受12周治疗（B组，n=23）。治疗方案为每日口服西米普明150mg和索磷布韦400mg。主要疗效终点为计划治疗结束后12周持续病毒学应答（SVR12）。全程评估安全性和耐受性。总体而言，92%（95%CI：82-97）的患者实现了SVR12；A1组为75%（15/20），A2组和B组为100%。未实现SVR12的患者（n=5）在治疗后的前32天内出现病毒复发，且均为既往Peg-IFN/RBV无应答者。最常报告的治疗中出现的不良事件（TEAE）为无症状脂肪酶升高（14%）、瘙痒（14%）、头痛（13%）和高胆红素血症（11%）。无患者因TEAE停药。总之，西米普明联合索磷布韦治疗12周，在HCV基因4型感染、有或无代偿期肝硬化的患者中实现了100%的SVR率（ClinicalTrials.gov：NCT02278419）。不良事件和实验室检查结果良好，与之前西米普明联合索磷布韦8周和12周治疗方案的数据一致。
