Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: the randomized PILLAR study.
Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: the randomized PILLAR study.
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DOI：
10.1002/hep.26641
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发表时间：
2013-12
期刊：
影响因子：
13.5
通讯作者：
Beumont-Mauviel, Maria
中科院分区：
文献类型：
--
作者：
Fried, Michael W.;Buti, Maria;Dore, Gregory J.;Flisiak, Robert;Ferenci, Peter;Jacobson, Ira;Marcellin, Patrick;Manns, Michael;Nikitin, Igor;Poordad, Fred;Sherman, Morris;Zeuzem, Stefan;Scott, Jane;Gilles, Leen;Lenz, Oliver;Peeters, Monika;Sekar, Vanitha;De Smedt, Goedele;Beumont-Mauviel, Maria
IIb期、双盲、安慰剂对照PILLAR试验研究了两种不同剂量的simeprevir（SMV）每日一次（QD）联合聚乙二醇干扰素（Peg-IFN）-α-2a和ribavirin（RBV）治疗未经治疗的HCV基因型1感染患者的疗效和安全性。患者被随机分配到五种治疗中的一种：SMV（75或150 mg QD）12或24周或安慰剂，加Peg-IFN和RBV。如果满足反应指导治疗（RGT）标准，SMV组患者在第24周停止所有治疗;不符合RGT的患者继续接受Peg-IFN和RBV治疗，直至第48周，安慰剂对照组患者也是如此。在计划治疗结束后24周测量的持续病毒学应答（SVR）率（SVR 24）在SMV组为74.7%-86.1%，对照组为64.9%（所有比较[SMV与安慰剂]的P < 0.05，但SMV 75 mg持续24周除外）。68.0%-75.6%的SMV治疗患者和5.2%的安慰剂对照患者实现了快速病毒学应答（第4周时HCV RNA <25 IU/mL，检测不到）。根据RGT标准，79.2%-86.1%的SMV治疗患者在第24周完成治疗;其中85.2%-95.6%随后达到SVR 24。SMV和安慰剂对照组的不良事件特征基本相似，但轻度可逆性高胆红素血症除外，无血清转氨酶异常，与较高剂量SMV相关。与Peg-IFN和RBV单独治疗相比，SMV QD联合Peg-IFN和RBV显著改善了SVR率，并使大多数患者的治疗持续时间缩短至24周。
The phase IIb, double-blind, placebo-controlled PILLAR trial investigated the efficacy and safety of two different simeprevir (SMV) doses administered once-daily (QD) with pegylated interferon (Peg-IFN)-α-2a and ribavirin (RBV) in treatment-naïve patients with HCV genotype 1 infection. Patients were randomized to one of five treatments: SMV (75 or 150 mg QD) for 12 or 24 weeks or placebo, plus Peg-IFN and RBV. Patients in the SMV arms stopped all treatment at week 24 if response-guided therapy (RGT) criteria were met; patients not meeting RGT continued with Peg-IFN and RBV until week 48, as did patients in the placebo control group. Sustained virologic response (SVR) rates measured 24 weeks after the planned end of treatment (SVR24) were 74.7%-86.1% in the SMV groups versus 64.9% in the control group (P < 0.05 for all comparisons [SMV versus placebo], except SMV 75 mg for 24 weeks). Rapid virologic response (HCV RNA <25 IU/mL undetectable at week 4) was achieved by 68.0%-75.6% of SMV-treated and 5.2% of placebo control patients. According to RGT criteria, 79.2%-86.1% of SMV-treated patients completed treatment by week 24; 85.2%-95.6% of these subsequently achieved SVR24. The adverse event profile was generally similar across the SMV and placebo control groups, with the exception of mild reversible hyperbilirubinemia, without serum aminotransferase abnormalities, associated with higher doses of SMV. SMV QD in combination with Peg-IFN and RBV significantly improves SVR rates, compared with Peg-IFN and RBV alone, and allows the majority of patients to shorten their therapy duration to 24 weeks.
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