title: All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection: a sub-analysis in Asian patients from the HALLMARK DUAL study.
abstract: Daclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b (GT-1b) infection in the HALLMARK DUAL trial. This post hoc analysis was conducted to determine the efficacy and safety of this treatment in Asian patients.
  
  
  
  Treatment-naive patients were randomly assigned (2:1; double-blinded) to receive DCV (60 mg once daily) plus ASV (100 mg twice daily) or placebo for 12 weeks. Subsequently, placebo patients entered another study, and the remaining patients continued treatment for an additional 12 weeks. Non-responders to peginterferon/ribavirin and ineligible/intolerant patients received dual therapy for 24 weeks. Sustained virological response at post-treatment Week 12 [sustained virological response (SVR)12] and safety outcomes were evaluated.
  
  
  
  This post hoc analysis included 186 Asian patients (Korean, 78; Taiwanese, 85; others, 23), of whom 32.3% were cirrhotic. SVR12 was observed in 92.3, 78.6 and 80.0% of treatment-naive, ineligible/intolerant and non-responder patients, respectively, and was comparable with non-Asian patients. SVR12 by baseline factors including age, viral load, interleukin-28B genotype and cirrhosis status was similar between the Asian sub-cohorts. Among 18 Asian patients with NS5A-Y93H or NS5A-L31M/V resistance-associated variants (RAVs), seven patients achieved SVR12. Multivariate regression analysis showed a significant influence of NS5A RAVs in both Asian and non-Asian cohorts. The incidence of serious adverse events in Asian patients was low (7.2%). Two Taiwanese patients had elevated alanine aminotransferase (≥5.1 × ULN); both achieved SVR12.
  
  
  
  All-oral dual therapy with DCV + ASV resulted in high SVR rates and was well tolerated in Asian patients with HCV GT-1b infection.
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. kaojh@ntu.edu.tw.
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.affiliation: Department of Internal Medicine, Inje University Busan-Paik Hospital, Busan, Republic of Korea.
authors.forename: Youn-Jae
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Pusan National University, Busan, Republic of Korea.
authors.forename: Jeong
authors.initials: J
authors.lastname: Heo
authors.affiliation: Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Lim
authors.affiliation: China Medical University, School of Medicine, Taichung, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.affiliation: Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
authors.affiliation: Global Biometric Sciences, Bristol-Myers Squibb, Braine-l'Alleud, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Torbeyns
authors.affiliation: Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Hughes
authors.affiliation: Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Rafia
authors.initials: R
authors.lastname: Bhore
authors.affiliation: Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Noviello
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D044466:Asian People; D002219:Carbamates; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007391:International Cooperation; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D000072230:Sustained Virologic Response; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D012367:RNA, Viral; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; D000410:Alanine Transaminase; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
keywords: Asia; asunaprevir; daclatasvir; genotype 1b