Re-treatment of Patients With Chronic Hepatitis C Who Do Not Respond to Peginterferon-α2b A Randomized Trial
Re-treatment of Patients With Chronic Hepatitis C Who Do Not Respond to Peginterferon-α2b A Randomized Trial
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DOI：
10.7326/0003-4819-150-8-200904210-00007
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发表时间：
2009-04-21
影响因子：
39.2
通讯作者：
Tietz, Andreas
中科院分区：
文献类型：
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作者：
Jensen, Donald M.;Marcellin, Patrick;Tietz, Andreas
背景：许多慢性丙型肝炎患者对聚乙二醇化干扰素加利巴韦林治疗没有反应。目的：评价聚乙二醇干扰素- α 2a联合利巴韦林对聚乙二醇干扰素- α 2b联合利巴韦林无效的再治疗效果。设计：2003年9月至2007年2月间进行的随机平行组试验。患者和研究人员并没有对干预分配视而不见。随机分配集中，计算机生成，并按地理区域，丙型肝炎病毒（HCV）基因型和组织学诊断分层。环境：106个国际中心。患者：950例对聚乙二醇干扰素- α 2b +利巴韦林治疗12周或更长时间无反应。干预：聚乙二醇干扰素- α 2a， 360 μ g/周，持续12周，然后180 μ g/周完成72周（A组）或48周（B组），或聚乙二醇干扰素- α 2a， 180 μ g/周，持续72周（C组）或48周（D组）。所有患者均给予利巴韦林，1000或1200mg /d。测量：持续病毒学反应（SVR），定义为治疗结束后24周无法检测到（< 50 IU/mL） HCV RNA水平。结果：A组（n = 317）、B组（n = 156）、C组（n = 156）、D组（n = 313）的SVR分别为16%、7%、14%、9%，A组与D组[主要比较]的相对危险度[RR]为1.80 [95% CI, 1.17 ~ 2.77]；P = 0.006)。延长治疗时间增加SVR率（72周16% [A组和C组]，48周8% [B组和D组]；RR, 2.00 [CI, 1.32 ~ 3.02]; P < 0.001）。A组和B组中21%的患者在第12周达到完全病毒抑制（HCV RNA水平< 50 IU/mL）， C组和d组中13%的患者在第12周达到完全病毒抑制，SVR分别为49%（157例患者中77例）和4%（719例患者中32例）。局限性：聚乙二醇干扰素- α 2a加利巴韦林无应答者未被评估。结论：对聚乙二醇干扰素- α 2b联合利巴韦林治疗无反应的患者再治疗72周，与再治疗48周相比，SVR率显著增加。总体SVR率很低，但最有可能对再次治疗有反应的患者可以在第12周确定。
Background: Many patients with chronic hepatitis C have not responded to therapy with pegylated interferon plus ribavirin.Objective: To evaluate use of peginterferon-alpha 2a plus ribavirin to re-treat nonresponders to peginterferon-alpha 2b plus ribavirin.Design: Randomized, parallel-group trial conducted between September 2003 and February 2007. Patients and researchers were not blinded to intervention assignment. Random assignment was centralized, computer-generated, and stratified by geographic region, hepatitis C virus (HCV) genotype, and histologic diagnosis.Setting: 106 international centers.Patients: 950 nonresponders to 12 or more weeks of therapy with peginterferon-alpha 2b plus ribavirin.Intervention: Peginterferon-alpha 2a, 360 mu g/wk, for 12 weeks, then 180 mu g/wk to complete 72 weeks (group A) or 48 weeks (group B), or peginterferon-alpha 2a, 180 mu g/wk for 72 weeks (group C) or 48 weeks (group D). All patients received ribavirin, 1000 or 1200 mg/d.Measurements: Sustained virologic response (SVR), defined as un-detectable (< 50 IU/mL) HCV RNA levels 24 weeks after the end of treatment.Results: The SVR rates in groups A (n = 317), B (n = 156), C (n = 156), and D (n = 313) were 16%, 7%, 14%, and 9%, respectively relative risk [RR] for group A vs. group D [the primary comparison], 1.80 [95% CI, 1.17 to 2.77]; P = 0.006). Extended treatment duration increased SVR rates (16% for 72 weeks [groups A and C] vs. 8% for 48 weeks [groups B and D]; RR, 2.00 [CI, 1.32 to 3.02]; P < 0.001). Complete viral suppression (HCV RNA level < 50 IU/mL) at week 12 was achieved in 21% of patients in groups A and B and 13% of those in groups C and D. Rates of SVR were 49% (77 of 157 patients) and 4% (32 of 719 patients) among those with and without complete viral suppression at week 12, respectively.Limitation: Nonresponders to peginterferon-alpha 2a plus ribavirin were not evaluated.Conclusion: Re-treating nonresponders to therapy with peginterferon-alpha 2b plus ribavirin for 72 weeks significantly increases SVR rates compared with re-treating them for 48 weeks. The overall SVR rate was low, but patients who are most likely to respond to re-treatment can be identified at week 12.