https://scholars.lib.ntu.edu.tw/handle/123456789/581862
標題: | Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1 | 作者: | JIA-HORNG KAO Yu M.-L. Peng C.-Y. Heo J. Chu C.-J. Chang T.-T. Lee Y.-J. Hu T.-H. Yoon K.T. Paik S.W. Lim Y.S. Ahn S.H. Isakov V. McPhee F. Hu W. Scott Swenson E. Yin P.D. Treitel M. |
關鍵字: | Asia; hepatitis; NS5A; treatment | 公開日期: | 2017 | 出版社: | Blackwell Publishing | 卷: | 32 | 期: | 12 | 起(迄)頁: | 1998-2005 | 來源出版物: | Journal of Gastroenterology and Hepatology (Australia) | 摘要: | Background and Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30?mg, asunaprevir (NS3 inhibitor) 200?mg, and beclabuvir (NS5B inhibitor) 75?mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n?=?138) or treatment-experienced (n?=?31), received twice-daily DCV-TRIO for 12?weeks with 24?weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. Results: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9–99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8–100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n?=?8) and genotype-1b (n?=?157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions. ? 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85033483487&doi=10.1111%2fjgh.13796&partnerID=40&md5=59e2ca6e1002b74670719eadfddd129d https://scholars.lib.ntu.edu.tw/handle/123456789/581862 |
ISSN: | 0815-9319 | DOI: | 10.1111/jgh.13796 | SDG/關鍵字: | alanine aminotransferase; aspartate aminotransferase; asunaprevir plus beclabuvir plus daclatasvir; bilirubin; nonstructural protein 5A; 8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide; asunaprevir; benzazepine derivative; BMS-790052; imidazole derivative; indole derivative; isoquinoline derivative; sulfonamide; adult; aged; alanine aminotransferase blood level; Article; aspartate aminotransferase blood level; bilirubin blood level; chronic hepatitis C; cohort analysis; compensated liver cirrhosis; controlled study; coughing; diarrhea; drug efficacy; drug tolerability; drug withdrawal; faintness; fatigue; female; genetic polymorphism; headache; Hepatitis C virus genotype 1; human; hypertransaminasemia; major clinical study; male; multicenter study; myalgia; phase 3 clinical trial; priority journal; pruritus; Russian Federation; South Korea; sustained virologic response; Taiwan; treatment outcome; treatment response; upper respiratory tract infection; chronic hepatitis C; drug combination; follow up; genetics; genotype; Hepacivirus; middle aged; very elderly; virology; young adult; Adult; Aged; Aged, 80 and over; Benzazepines; Cohort Studies; Drug Combinations; Female; Follow-Up Studies; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Indoles; Isoquinolines; Male; Middle Aged; Republic of Korea; Russia; Sulfonamides; Taiwan; Treatment Outcome; Young Adult |
顯示於: | 臨床醫學研究所 |
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