Welzel T M, Hinrichsen H, Sarrazin C, Buggisch P, Baumgarten A, Christensen S, Berg T, Mauss S, Teuber G, Stein K, Deterding K, van Bömmel F, Heyne R, John C, Zimmermann T, Lutz T, Schott E, Hettinger J, Kleine H, König B, Hüppe D, Wedemeyer H
Department of Medicine 1, University Hospital, J.W. Goethe University, Frankfurt am Main, Germany.
Gastroenterology-Hepatology Center Kiel, Kiel, Germany.
J Viral Hepat. 2017 Oct;24(10):840-849. doi: 10.1111/jvh.12708. Epub 2017 May 25.
Real-world studies are relevant to complement clinical trials on novel antiviral therapies against chronic hepatitis C; however, clinical practice data are currently limited. This study investigated effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r)±dasabuvir (DSV)±ribavirin (RBV) for treatment of HCV genotype (GT) 1 and GT4 infection in a large real-world cohort. The German Hepatitis C Registry is an observational cohort study prospectively collecting clinical practice data on direct-acting antiviral therapies. Patients with GT1/4 infection treated with OBV/PTV/r±DSV±RBV were analysed. Effectiveness was assessed by sustained virologic response in 558 patients who reached post-treatment week 12 (SVR12). Safety is reported in 1017 patients who initiated treatment. Of the patients, 892 (88%) had GT1 and 125 (12%) had GT4 infection. Prior treatment experience and cirrhosis were reported in 598 (59%) and 228 (22%) patients, respectively. Overall, SVR12 (mITT) was 96% (486/505) in GT1- and 100% (53/53) in GT4 patients. SVR12 rates were high across subgroups including patients with cirrhosis (95%, 123/129), patients with moderate to severe renal impairment (100%, 34/34), and subgroups excluded from registrational trials like patients ≥70 years (96%, 64/67) and failures to prior protease inhibitor treatment (96%, 46/48). Adverse events (AEs) and serious AEs were reported in 52% (525/1017) and 2% (21/1017) of patients, respectively, and led to treatment discontinuation in 1.5% (15/1017) of patients. OBV/PTV/r±DSV±RBV was effective and generally well tolerated for treatment of HCV infection in clinical practice.
真实世界研究对于补充新型抗丙型肝炎病毒疗法的临床试验具有重要意义；然而，目前临床实践数据有限。本研究调查了奥比他韦/帕利哌韦/利托那韦（OBV/PTV/r）±达沙布韦（DSV）±利巴韦林（RBV）治疗丙型肝炎病毒基因型（GT）1和GT4感染在一个大型真实世界队列中的有效性和安全性。德国丙型肝炎登记处是一项观察性队列研究，前瞻性收集直接抗病毒疗法的临床实践数据。对接受OBV/PTV/r±DSV±RBV治疗的GT1/4感染患者进行了分析。通过558例达到治疗后第12周的持续病毒学应答（SVR12）评估有效性。报告了1017例开始治疗患者的安全性。患者中，892例（88%）为GT1感染，125例（12%）为GT4感染。分别有598例（59%）和228例（22%）患者报告了既往治疗史和肝硬化情况。总体而言，GT1患者的SVR12（意向性分析）为96%（486/505），GT4患者为100%（53/53）。包括肝硬化患者（95%，123/129）、中度至重度肾功能损害患者（100%，34/34）以及注册试验排除的亚组如≥70岁患者（96%，64/67）和既往蛋白酶抑制剂治疗失败者（96%，46/48）在内的各亚组SVR12率均较高。分别有52%（525/1017）和2%（21/1017）的患者报告了不良事件（AE）和严重不良事件，1.5%（15/1017）的患者因不良事件导致治疗中断。在临床实践中，OBV/PTV/r±DSV±RBV治疗丙型肝炎病毒感染有效且总体耐受性良好。
