Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0595, USA.
N Engl J Med. 2011 Sep 15;365(11):1014-24. doi: 10.1056/NEJMoa1014463.
Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5%) to compare rates of sustained virologic response among patients receiving two treatment durations.
We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 μg per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon-ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48.
Of the 540 patients, a total of 352 (65%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92%) in the T12PR24 group and 140 (88%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95% confidence interval, -2 to 11), establishing noninferiority. Adverse events included rash (in 37% of patients, severe in 5%) and anemia (in 39%, severe in 6%). Discontinuation of all the study drugs was based on adverse events in 18% of patients overall, as well as in 1% of patients (all of whom were randomly assigned) in the T12PR24 group and 12% of the patients randomly assigned to the T12PR48 group (P<0.001).
In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon-ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.).
慢性丙型肝炎病毒（HCV）基因型 1 感染患者通常需要 48 周的聚乙二醇干扰素-利巴韦林治疗以获得持续病毒学应答。我们设计了一项非劣效性试验（非劣效性边界，-10.5%），以比较接受两种治疗持续时间的患者的持续病毒学应答率。
我们招募了未经治疗的慢性 HCV 基因型 1 感染患者。所有患者均接受替拉瑞韦 750mg 每 8 小时一次、聚乙二醇干扰素 alfa-2a 每周 180μg 和利巴韦林每天 1000-1200mg，治疗 12 周（T12PR12），然后继续给予聚乙二醇干扰素-利巴韦林。在第 20 周后，具有扩展快速病毒学应答（第 4 和 12 周时 HCV RNA 水平不可检测）的患者随机分配后，再接受为期 4 周（T12PR24）或 28 周（T12PR48）的双重治疗。未达到扩展快速病毒学应答的患者被分配到 T12PR48。
在 540 名患者中，共有 352 名（65%）患者达到了扩展快速病毒学应答。总的持续病毒学应答率为 72%。在 322 名具有扩展快速病毒学应答的随机分组患者中，T12PR24 组有 149 名（92%）和 T12PR48 组有 140 名（88%）患者获得了持续病毒学应答（绝对差异为 4 个百分点；95%置信区间，-2 至 11），表明非劣效性。不良事件包括皮疹（37%的患者，严重的 5%）和贫血（39%，严重的 6%）。由于不良事件，所有研究药物的停药率总体为 18%，T12PR24 组为 1%（所有患者均随机分配），T12PR48 组为 12%（随机分配的患者）（P<0.001）。
在这项研究中，在未接受治疗的慢性 HCV 感染患者中，与利巴韦林联合聚乙二醇干扰素治疗 48 周相比，替拉瑞韦治疗 12 周的方案在第 4 和 12 周时 HCV RNA 不可检测的患者中具有非劣效性，近三分之二的患者达到了扩展快速病毒学应答。（由 Vertex 制药公司和 Tibotec 公司资助；ILLUMINATE 临床试验。gov 编号，NCT00758043）。
