Institut Klinické a Experimentální Medicíny (IKEM), Prague, Czech Republic.
Budai Hepatólogiai Centrum, Budapest, Hungary.
J Hepatol. 2016 Dec;65(6):1112-1119. doi: 10.1016/j.jhep.2016.07.050. Epub 2016 Aug 16.
BACKGROUND & AIMS: Direct-acting antiviral agents have improved treatment outcomes for patients with hepatitis C virus (HCV) infection; however, head-to-head comparisons are limited. The C-EDGE Head-2-Head Study compared the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) with sofosbuvir plus pegylated interferon/ribavirin (SOF/PR) in patients with HCV infection.
This was a randomized, open-label, phase III trial. Two hundred fifty-seven patients with HCV genotype (GT)1 or 4 infection and baseline viral load >10,000IU/ml were randomized to receive 12weeks of EBR/GZR 50mg/100mg once daily (n=129) or sofosbuvir (400mg once daily) plus PR (n=128). Primary efficacy objective was sustained virologic response 12weeks after the end of therapy (SVR12, HCV RNA <15IU/ml). The primary safety objective was the proportion of patients experiencing a tier 1 safety event.
The majority of patients were non-cirrhotic (83.1%), treatment-naïve (74.9%) and had HCV GT1b infection (82.0%). SVR12 rates were 99.2% (128/129) and 90.5% (114/126) in the EBR/GZR and SOF/PR groups, respectively. The estimated adjusted difference in SVR12 was 8.8% (95% confidence interval [CI], 3.6-15.3%). Because the lower bound of the 1-sided 1-sample exact test was greater than -10% and greater than zero, both non-inferiority and superiority of EBR/GZR vs. SOF/PR were established. The frequency of tier 1 safety events was lower among patients receiving EBR/GZR than SOF/PR (0.8% vs. 27.8%, between group difference, 27.0% [95% CI, -35.5% to -19.6%; p<0.001]).
EBR/GZR has a superior efficacy and safety profile in patients with HCV GT1 or 4 infection compared with SOF/PR.
The combination of elbasvir/grazoprevir for 12weeks was highly effective in treating patients with chronic hepatitis C, genotypes 1 or 4 infection. This regimen was more effective than sofosbuvir/pegylated interferon/ribavirin for 12weeks, and was notably superior in patients regarded as difficult to treat, including those with previous treatment failure, cirrhosis, or a high baseline viral load. The combination of elbasvir/grazoprevir also demonstrated a superior safety and tolerability profile based on fewer serious adverse events, no serious drug-related adverse events, and no treatment discontinuations.
Clinical trials.gov Identifier: NCT02358044.
直接作用抗病毒药物改善了丙型肝炎病毒（HCV）感染患者的治疗效果；然而，头对头比较有限。C-EDGE 头对头研究比较了 Elbasvir/Grazoprevir（EBR/GZR）与索磷布韦联合聚乙二醇干扰素/利巴韦林（SOF/PR）在 HCV 感染患者中的安全性和疗效。
这是一项随机、开放标签、III 期临床试验。257 例 HCV 基因型（GT）1 或 4 感染且基线病毒载量>10,000IU/ml 的患者被随机分为接受 12 周 EBR/GZR 50mg/100mg 每日一次（n=129）或索磷布韦（400mg 每日一次）联合 PR（n=128）治疗。主要疗效终点为治疗结束后 12 周持续病毒学应答（SVR12，HCV RNA<15IU/ml）。主要安全性终点为经历 1 级安全性事件的患者比例。
大多数患者无肝硬化（83.1%）、初治（74.9%）且 HCV GT1b 感染（82.0%）。EBR/GZR 和 SOF/PR 组的 SVR12 率分别为 99.2%（128/129）和 90.5%（114/126）。SVR12 的估计调整差异为 8.8%（95%置信区间 [CI]，3.6-15.3%）。由于单侧 1 样本精确检验的下限大于-10%且大于零，因此 EBR/GZR 与 SOF/PR 相比，非劣效性和优效性均成立。接受 EBR/GZR 治疗的患者发生 1 级安全性事件的频率低于接受 SOF/PR 治疗的患者（0.8% vs. 27.8%，组间差异为 27.0%[95%CI，-35.5%至-19.6%；p<0.001]）。
与 SOF/PR 相比，EBR/GZR 治疗 HCV GT1 或 4 感染患者的疗效和安全性更佳。
Elbasvir/grazoprevir 联合治疗 12 周可有效治疗慢性丙型肝炎，基因型 1 或 4 感染患者。该方案比索磷布韦联合聚乙二醇干扰素/利巴韦林治疗 12 周更有效，在被认为难以治疗的患者中，包括既往治疗失败、肝硬化或基线病毒载量较高的患者中，效果更为显著。Elbasvir/grazoprevir 联合方案的安全性和耐受性也更好，表现在不良事件较少、无严重药物相关不良事件和无治疗中断。
ClinicalTrials.gov 标识符：NCT02358044。
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