Lawitz Eric, Poordad Fred, Brainard Diana M, Hyland Robert H, An Di, Dvory-Sobol Hadas, Symonds William T, McHutchison John G, Membreno Fernando E
Texas Liver Institute, San Antonio, TX; University of Texas Health Science Center, San Antonio, TX.
Hepatology. 2015 Mar;61(3):769-75. doi: 10.1002/hep.27567. Epub 2015 Jan 30.
Sofosbuvir (SOF) in combination with ribavirin (RBV) for 12 or 24 weeks is the current standard of care for patients infected with hepatitis C virus (HCV) genotypes 2 and 3, respectively. However, in clinical trials treatment-experienced patients, particularly those with cirrhosis, had suboptimal sustained virological response (SVR) rates. We assessed the efficacy and safety of sofosbuvir plus peginterferon and ribavirin (SOF+Peg-IFN+RBV) administered for 12 weeks to treatment-experienced patients with HCV genotypes 2 and 3, with and without cirrhosis. We enrolled 47 patients in this open-label, nonrandomized, uncontrolled phase 2 study. The primary endpoint was the proportion of patients with SVR at 12 weeks after cessation of study treatment (SVR12). The overall rate of SVR12 was 89% (95% confidence interval [CI]: 77-97). Rates of SVR12 were higher in patients with genotype 2 than in those with genotype 3, 96% (95% CI: 78-100) and 83% (95% CI: 62-95), respectively. Rates of SVR12 were similar in patients with and without cirrhosis: for genotype 2, 93% of patients with cirrhosis and 100% of patients without cirrhosis achieved SVR12, and for genotype 3, the SVR12 rate was 83% in patients both with and without cirrhosis. One patient discontinued study treatment because of an adverse event and four patients experienced serious adverse events. The most common adverse events were influenza-like illness, fatigue, anemia, and neutropenia.
In treatment-experienced patients with HCV genotypes 2 and 3, 12-week administration of SOF+Peg-IFN+RBV provided high SVR rates, irrespective of cirrhosis status. No safety concerns were identified.
索磷布韦（SOF）联合利巴韦林（RBV）分别治疗12周或24周是目前丙型肝炎病毒（HCV）2型和3型感染患者的标准治疗方案。然而，在临床试验中，经治患者，尤其是那些患有肝硬化的患者，持续病毒学应答（SVR）率并不理想。我们评估了索磷布韦联合聚乙二醇干扰素和利巴韦林（SOF+聚乙二醇干扰素+RBV）治疗12周对经治的HCV 2型和3型患者（有或无肝硬化）的疗效和安全性。我们在这项开放标签、非随机、非对照的2期研究中纳入了47例患者。主要终点是研究治疗停止后12周时达到SVR的患者比例（SVR12）。SVR12的总体发生率为89%（95%置信区间[CI]：77-97）。2型患者的SVR12发生率高于3型患者，分别为96%（95%CI：78-100）和83%（95%CI：62-95）。有肝硬化和无肝硬化患者的SVR12发生率相似：对于2型，93%的肝硬化患者和100%的无肝硬化患者达到SVR12，对于3型，有肝硬化和无肝硬化患者的SVR12发生率均为83%。1例患者因不良事件停止研究治疗，4例患者发生严重不良事件。最常见的不良事件是流感样疾病、疲劳、贫血和中性粒细胞减少。
在经治的HCV 2型和3型患者中，12周的SOF+聚乙二醇干扰素+RBV治疗提供了较高的SVR率，无论肝硬化状态如何。未发现安全问题。
