Response-guided telaprevir combination treatment for hepatitis C virus infection.
Response-guided telaprevir combination treatment for hepatitis C virus infection.
复制标题
DOI：
10.1056/nejmoa1014463
复制
发表时间：
2011-09-15
期刊：
影响因子：
--
通讯作者：
ILLUMINATE Study Team
中科院分区：
文献类型：
--
作者：
Sherman KE;Flamm SL;Afdhal NH;Nelson DR;Sulkowski MS;Everson GT;Fried MW;Adler M;Reesink HW;Martin M;Sankoh AJ;Adda N;Kauffman RS;George S;Wright CI;Poordad F;ILLUMINATE Study Team
慢性感染1型丙型肝炎病毒的患者通常需要48周的聚乙二醇干扰素-利巴韦林治疗才能获得持续的病毒学应答。我们设计了一项非劣势试验(非劣势边缘，−10.5%)来比较接受两个疗程的患者的持续病毒学应答率。我们招募了之前没有接受过治疗的丙型肝炎病毒1型慢性感染患者。所有患者均接受T12PR12治疗(T12PR12)，每8小时1次，每次750 mg，每周1次，每次180μg，共12周。病毒学快速应答延长的患者(在第4周和第12周检测不到HCVRNA水平)在第20周后被随机分配到接受双重治疗4周或28周(T12PR24)或28周(T12PR48)。没有延长快速病毒学反应的患者被分配到T12PR48。在540名患者中，共有352名(65%)有延长的快速病毒学反应。总的持续病毒学应答率为72%。在被随机分配到研究组的322名快速病毒学应答延长的患者中，T12PR24组和T12PR48组分别有149例(92%)和140例(88%)有持续的病毒学应答(绝对差值4个百分点；95%可信区间，−2至11)，建立了非劣势。不良反应包括皮疹(37%的患者，重度为5%)和贫血(39%，重度为6%)。所有研究药物的停用是基于18%的患者总体上的不良事件，以及T12PR24组中1%的患者(所有患者都是随机分配的)和12%的随机分配到T12PR48组的患者(P<；0.001)。在这项研究中，在以前没有接受过治疗的慢性丙型肝炎病毒感染患者中，24周的聚乙二醇干扰素-利巴韦林方案，前12周使用telapvir，在第4周和12周未检测到丙型肝炎病毒核糖核酸的患者中，48周的方案不逊于相同的方案，近三分之二的患者实现了延长的快速病毒学反应。(由Vertex PharmPharmticals和Tibotec提供资金；照明ClinicalTrials.gov编号，NCT00758043。)
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.)