特拉匹韦与聚乙二醇干扰素联合或不联合利巴韦林用于慢性丙型肝炎病毒感染的治疗。

Telaprevir and peginterferon with or without ribavirin for chronic HCV infection.

作者信息

Hézode Christophe, Forestier Nicole, Dusheiko Geoffrey, Ferenci Peter, Pol Stanislas, Goeser Tobias, Bronowicki Jean-Pierre, Bourlière Marc, Gharakhanian Shahin, Bengtsson Leif, McNair Lindsay, George Shelley, Kieffer Tara, Kwong Ann, Kauffman Robert S, Alam John, Pawlotsky Jean-Michel, Zeuzem Stefan

机构信息

Assistance Publique-Hôpitaux de Paris, Henri Mondor Hospital, University of Paris 12 and INSERM Unité 955, Créteil, France.

出版信息

N Engl J Med. 2009 Apr 30;360(18):1839-50. doi: 10.1056/NEJMoa0807650.

DOI:10.1056/NEJMoa0807650

PMID:19403903

Abstract

BACKGROUND

In patients with chronic infection with hepatitis C virus (HCV) genotype 1, treatment with peginterferon alfa and ribavirin for 48 weeks results in rates of sustained virologic response of 40 to 50%. Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment.

METHODS

A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were randomly assigned to receive one of four treatments involving various combinations of telaprevir (1250 mg on day 1, then 750 mg every 8 hours), peginterferon alfa-2a (180 microg weekly), and ribavirin (dose according to body weight). The T12PR24 group (81 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks, followed by peginterferon alfa-2a and ribavirin for 12 more weeks. The T12PR12 group (82 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks. The T12P12 group (78 patients) received telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks. The PR48 (control) group (82 patients) received peginterferon alfa-2a and ribavirin for 48 weeks. The primary end point, a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy), was compared between the control group and the combined T12P12 and T12PR12 groups.

RESULTS

The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48% (77 of 160 patients), as compared with 46% (38 of 82) in the PR48 (control) group (P=0.89). The rate was 60% (49 of 82 patients) in the T12PR12 group (P=0.12 for the comparison with the PR48 group), as compared with 36% (28 of 78 patients) in the T12P12 group (P=0.003; P=0.20 for the comparison with the PR48 group). The rate was significantly higher in the T12PR24 group (69% [56 of 81 patients]) than in the PR48 group (P=0.004). The adverse events with increased frequency in the telaprevir-based groups were pruritus, rash, and anemia.

CONCLUSIONS

In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously, one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with standard therapy. Response rates were lowest with the regimen that did not include ribavirin. (ClinicalTrials.gov number, NCT00372385.)

摘要

背景

在慢性丙型肝炎病毒（HCV）1型感染患者中，聚乙二醇化干扰素α与利巴韦林联合治疗48周，持续病毒学应答率为40%至50%。特拉匹韦是HCV丝氨酸蛋白酶的特异性抑制剂，可能对HCV治疗有价值。

方法

共有334例慢性HCV 1型感染且未接受过治疗的患者被随机分配接受四种治疗方案之一，这些方案包含特拉匹韦（第1天1250 mg，之后每8小时750 mg）、聚乙二醇化干扰素α-2a（每周180 μg）和利巴韦林（根据体重给药）的不同组合。T12PR24组（81例患者）接受特拉匹韦、聚乙二醇化干扰素α-2a和利巴韦林治疗12周，随后再接受聚乙二醇化干扰素α-2a和利巴韦林治疗12周。T12PR12组（82例患者）接受特拉匹韦、聚乙二醇化干扰素α-2a和利巴韦林治疗12周。T12P12组（78例患者）接受特拉匹韦和聚乙二醇化干扰素α-2a，不使用利巴韦林，治疗12周。PR48（对照）组（82例患者）接受聚乙二醇化干扰素α-2a和利巴韦林治疗48周。比较对照组与T12P12组和T12PR12组合并组的主要终点，即持续病毒学应答（治疗结束后24周HCV RNA水平不可检测）。

结果

T12PR12组和T12P12组合并组的持续病毒学应答率为48%（160例患者中的77例），而PR48（对照）组为46%（82例中的38例）（P = 0.89）。T12PR12组的应答率为60%（82例患者中的49例）（与PR48组比较，P = 0.12），而T12P12组为36%（78例患者中的28例）（P = 0.003；与PR48组比较，P = 0.20）。T12PR24组的应答率（69% [81例患者中的56例]）显著高于PR48组（P = 0.004）。基于特拉匹韦的治疗组中发生率增加的不良事件为瘙痒、皮疹和贫血。