患者不能聚乙二醇干扰素Sofosbuvir有效

StephenW

Summary and Comment
Sofosbuvir Works for Patients Who Cannot Take Peginterferon

Two phase III studies confirm the efficacy of a sofosbuvir and ribavirin therapy in patients with HCV genotype 2 or 3 infection for whom peginterferon is not an option.

In patients infected with hepatitis C virus (HCV) genotype 2 or 3, treatment with peginterferon plus ribavirin has a sustained virologic response (SVR) of 70% to 85%. However, adverse effects of peginterferon are a barrier to treatment for many patients. Now, two industry-funded, phase III trials have evaluated the efficacy of sofosbuvir (400 mg daily) plus ribavirin (1000 mg–1200 mg daily) in these patients.

In a blinded, placebo-controlled trial, investigators randomized 280 patients for whom peginterferon therapy was not an option (e.g., adverse effects, contraindications for interferons, and patient refusal) to receive sofosbuvir/ribavirin or matching placebo for 12 weeks. In a blinded, active-control trial, researchers randomized 202 patients with prior nonresponse to peginterferon therapy to receive 12 or 16 weeks of sofosbuvir/ribavirin. The primary endpoint in both studies was SVR at 12 weeks after therapy ended.

In patients for whom peginterferon therapy was not an option, SVR was 78% for treatment with sofosbuvir/ribavirin compared with 0% for placebo (P<0.001). In previously treated patients, SVR was 50% for 12 weeks of therapy versus 73% for 16 weeks (P<0.001). SVR rates were lower for patients with genotype 3 versus genotype 2 in both treatment-naive patients (61% vs. 93%) and treatment-experienced patients who received therapy for 12 weeks (30% vs. 86%) or 16 weeks (62% vs. 94%).

SVR rates were lower in patients with cirrhosis than without, both in treatment-naive patients (overall, 61% vs. 81%; genotype 3 vs. 2, 21% vs. 94%) and treatment-experienced patients (overall, 66% vs. 76%; genotype 3 vs. 2 in 16-week group, 61% vs. 78%). In both studies, investigators found no evidence of resistance development, and discontinuation rates were low (1%–2%).

Comment: Oral sofosbuvir plus ribavirin is effective in patients with HCV genotypes 2 or 3 for whom peginterferon-based therapy is not an option or was previously ineffective. Of note, these sustained virologic response rates for sofosbuvir plus ribavirin are comparable to or higher than those previously reported for therapy with peginterferon plus ribavirin in this population.

— Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology May 24, 2013

Citation(s):

Jacobson IM et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013 May 16; 368:1867. (http://dx.doi.org/10.1056/NEJMoa1214854)

StephenW

两个III期临床试验确认的sofosbuvir和三氮唑核苷治疗的疗效的患者有HCV基因型2或3感染，对他们来说，聚乙二醇化是不是一种选择。

在感染丙型肝炎病毒（HCV）基因型2或3，与聚乙二醇干扰素联合利巴韦林治疗的患者中具有持续病毒学反应（SVR）的70％至85％。然而，聚乙二醇化的不利影响的许多患者的治疗的一个障碍。现在，两个行业资助，III期临床试验已评估sofosbuvir（每日400毫克）加利巴韦林（每日1000毫克，1200毫克），在这些患者中的疗效。

在一项双盲，安慰剂对照试验中，随机调查280名患者中，聚乙二醇干扰素治疗是不是一种选择（例如，副作用，禁忌症为干扰素，患者拒绝）接收sofosbuvir /利巴韦林或匹配安慰剂12周。在一项双盲，主动控制试验中，研究人员事先聚乙二醇干扰素治疗无应答的202例随机接受12周或16周的sofosbuvir /利巴韦林。在这两项研究的主要终点是在12周治疗结束后的SVR。

在聚乙二醇干扰素治疗患者对他们来说不是一个好的选择，SVR为78％与sofosbuvir /利巴韦林治疗相比，安慰剂组为0％（P <0.001）。在以前治疗的患者，SVR率为50％，治疗12周与73％，连续16周（P <0.001）。 SVR率较低基因型3比2基因型的患者在治疗初治患者（61％比93％）和治疗经验的患者接受治疗12周（30％比86％）或16周（62 ％对94％）。

SVR率较低，比没有，无论是在治疗初治患者（总体而言，61％与81％;基因型3比2，21％与94％）和治疗经验的患者（总体而言，66％的肝硬化患者比76％;基因型3比2在16周组，61％与78％）。在这两项研究中，研究者发现，没有证据证明耐药性的发展，停药率较低（1％-2％）。

评论：口腔sofosbuvir加利巴韦林是基于聚乙二醇干扰素治疗丙型肝炎病毒基因型2或3人是不是一种选择，或者是以前无效的患者有效。值得注意的是，这些持续病毒学应答率为sofosbuvir加利巴韦林相若或高于以前报道的在这一人群中与聚乙二醇干扰素联合利巴韦林治疗。

- 与Atif扎曼，MD，MPH

期刊观看消化科2013年5月24日发布

引用（S）：

雅各布森IM等。 Sofosbuvir丙型肝炎基因型患者无治疗方案2或3。新英格兰医学杂志2013年5月16 368:1867。 （http://dx.doi.org/10.1056/NEJMoa1214854）