Jia-Horng Kao1, Youn-Jae Lee2, Jeong Heo3, Sang-Hoon Ahn4, Young-Suk Lim5, Cheng-Yuan Peng6, Ting-Tsung Chang7, Anne Torbeyns8, Eric Hughes9, Rafia Bhore9, Stephanie Noviello9. 1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. kaojh@ntu.edu.tw. 2. Department of Internal Medicine, Inje University Busan-Paik Hospital, Busan, Republic of Korea. 3. Department of Internal Medicine, Pusan National University, Busan, Republic of Korea. 4. Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea. 5. Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 6. China Medical University, School of Medicine, Taichung, Taiwan. 7. Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 8. Global Biometric Sciences, Bristol-Myers Squibb, Braine-l'Alleud, Belgium. 9. Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
Abstract
BACKGROUND & AIMS: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. METHODS: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. RESULTS: 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. CONCLUSIONS: All-oral dual therapy with DCV + ASV resulted in high SVR rates and was well tolerated in Asian patients with HCV GT-1b infection.
RCT Entities:
BACKGROUND & AIMS: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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: Petra E de Ruiter; Yashna Gadjradj; Robert J de Knegt; Herold J Metselaar; Jan Nm Ijzermans; Luc Jw van der Laan Journal: World J Transplant Date: 2018-09-10
Authors: Jae Young Oh; Byung Seok Kim; Chang Hyeong Lee; Jeong Eun Song; Heon Ju Lee; Jung Gil Park; Jae Seok Hwang; Woo Jin Chung; Byoung Kuk Jang; Young Oh Kweon; Won Young Tak; Soo Young Park; Se Young Jang; Jeong Ill Suh; Sang Gyu Kwak Journal: Korean J Intern Med Date: 2018-05-25 Impact factor: 2.884