Toyota Joji, Karino Yoshiyasu, Suzuki Fumitaka, Ikeda Fusao, Ido Akio, Tanaka Katsuaki, Takaguchi Koichi, Naganuma Atsushi, Tomita Eiichi, Chayama Kazuaki, Fujiyama Shigetoshi, Inada Yukiko, Yoshiji Hitoshi, Watanabe Hideaki, Ishikawa Hiroki, Hu Wenhua, McPhee Fiona, Linaberry Misti, Yin Philip D, Swenson Eugene Scott, Kumada Hiromitsu
Department of Gastroenterology, Sapporo-Kosei General Hospital, 8-5 Higashi Kita-3-jo Chuo-ku, Sapporo-shi, Hokkaido, Japan.
Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan.
J Gastroenterol. 2017 Mar;52(3):385-395. doi: 10.1007/s00535-016-1245-6. Epub 2016 Aug 9.
DCV-TRIO, a fixed-dose combination of daclatasvir (pangenotypic NS5A inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (non-nucleoside NS5B inhibitor), has achieved high rates of sustained virologic response at post-treatment Week 12 (SVR12) in phase 3 studies.
In this phase 3 study, DCV-TRIO for 12 weeks and daclatasvir plus asunaprevir (DUAL) for 24 weeks were studied in Japanese patients infected with HCV genotype 1 (99 % genotype 1b).
SVR12 rates ≥95 % were achieved in both treatment-naive (N = 152) and interferon-experienced (N = 65) cohorts treated with DCV-TRIO for 12 weeks and were comparable across patient subgroups, including patients aged ≥65 years and those with cirrhosis. DUAL recipients (N = 75) had an SVR12 rate of 87 %. In the absence of baseline resistance-associated polymorphisms at positions NS5A-Y93H or -L31, SVR12 rates were 98 % with DCV-TRIO or DUAL. Among genotype 1b-infected patients with baseline Y93H or L31 polymorphisms, 35/38 (92 %) DCV-TRIO recipients, and 7/16 (44 %) DUAL recipients achieved SVR12. Adverse events, mostly liver related, led to treatment discontinuation in 10 % of DCV-TRIO recipients. In this group, SVR12 was achieved by 3/9 patients who discontinued before Week 4 and by 12/12 patients who completed ≥4 weeks of DCV-TRIO. Treatment-related serious adverse events occurred in 4 and 3 % of DCV-TRIO and DUAL recipients, respectively. Seven patients (9 %) discontinued DUAL due to adverse events. No deaths occurred.
SVR12 was achieved by 96 % of Japanese patients with HCV genotype 1 infection after 12 weeks of treatment with the DCV-TRIO regimen. DCV-TRIO and DUAL exhibited comparable safety profiles.
DCV-TRIO是一种固定剂量组合药物，由达卡他韦（泛基因型NS5A抑制剂）、阿舒瑞韦（NS3/4A蛋白酶抑制剂）和贝克洛维（非核苷类NS5B抑制剂）组成，在3期研究中，其在治疗后第12周（SVR12）时实现了较高的持续病毒学应答率。
在这项3期研究中，对感染丙型肝炎病毒1型（99%为1b基因型）的日本患者，研究了使用DCV-TRIO治疗12周和使用达卡他韦加阿舒瑞韦（DUAL）治疗24周的疗效。
接受DCV-TRIO治疗12周的初治患者（N = 152）和曾接受干扰素治疗的患者（N = 65）的SVR12率均≥95%，在各患者亚组中相当，包括年龄≥65岁的患者和肝硬化患者。接受DUAL治疗的患者（N = 75）的SVR12率为87%。在NS5A-Y93H或-L31位点不存在基线耐药相关多态性的情况下，DCV-TRIO或DUAL治疗的SVR12率为98%。在感染1b基因型且具有基线Y93H或L31多态性的患者中，35/38（92%）接受DCV-TRIO治疗的患者和7/16（44%）接受DUAL治疗的患者实现了SVR12。不良事件大多与肝脏相关，导致10%接受DCV-TRIO治疗的患者停药。在该组中，在第4周前停药的9名患者中有3名实现了SVR12，而完成≥4周DCV-TRIO治疗的12名患者中有12名实现了SVR12。治疗相关严重不良事件分别发生在4%接受DCV-TRIO治疗的患者和3%接受DUAL治疗的患者中。7名患者（9%）因不良事件停用DUAL。无死亡病例。
DCV-TRIO方案治疗12周后，96%感染丙型肝炎病毒1型的日本患者实现了SVR12。DCV-TRIO和DUAL表现出相当的安全性。
