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High Sustained Virologic Response to Daclatasvir Plus Asunaprevir in Elderly and Cirrhotic Patients with Hepatitis C Virus Genotype 1b Without Baseline NS5A Polymorphisms

 Fiona McPhee  ;  Yoshiyuki Suzuki  ;  Joji Toyota  ;  Yoshiyasu Karino  ;  Kasuaki Chayama  ;  Yoshiiku Kawakami  ;  Min Lung Yu  ;  Sang Hoon Ahn  ;  Hiroki Ishikawa  ;  Rafia Bhore  ;  Nannan Zhou  ;  Dennis Hernandez  ;  Patricia Mendez  ;  Hiromitsu Kumada 
 ADVANCES IN THERAPY, Vol.32(7) : 637-649, 2015 
Journal Title
Issue Date
Adult ; Aged ; Antiviral Agents/administration & dosage ; Antiviral Agents/therapeutic use* ; Asian Continental Ancestry Group ; Drug Resistance, Viral/genetics ; Drug Therapy, Combination ; Genotype ; Hepacivirus/genetics* ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy* ; Humans ; Imidazoles/administration & dosage ; Imidazoles/therapeutic use* ; Isoquinolines/administration & dosage ; Isoquinolines/therapeutic use* ; Japan ; Liver Cirrhosis/drug therapy* ; Liver Cirrhosis/etiology ; Middle Aged ; Phosphoproteins/genetics ; Polymorphism, Genetic ; Sulfonamides/administration & dosage ; Sulfonamides/therapeutic use* ; Viral Nonstructural Proteins/genetics ; Young Adult
Asunaprevir ; Daclatasvir ; Drug resistance ; Infectious diseases ; Viral hepatitis
INTRODUCTION: Oral daclatasvir (DCV; pangenotypic NS5A inhibitor) plus asunaprevir (ASV; NS3 protease inhibitor) is approved in Japan and Korea for treatment of chronic hepatitis C virus (HCV) genotype 1. Response to DCV + ASV is affected by DCV resistance-associated polymorphisms (RAPs) in HCV NS5A. The prevalence and influence of these RAPs on 12-week sustained virologic response (SVR12) to DCV + ASV was evaluated in Asian and non-Asian patients. METHODS: Data were pooled from 5 national and international studies of patients with HCV genotype 1b (GT-1b) receiving DCV + ASV at their recommended doses. Baseline NS5A RAPs and their effect on SVR12 were assessed overall, in older (≥65 years) patients, patients with cirrhosis, and in patients stratified by baseline HCV RNA or prior treatment experience with interferon-based therapy. RESULTS: Baseline NS5A sequences were available from 988 patients (374 Japanese; 125 Korean/Taiwanese; 489 from non-Asian countries), 979 of whom were assessed for SVR12. Pretreatment NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were present in 18% of Japanese and 12-13% of non-Japanese patients; these RAPs reduced SVR12 by 54.9% overall (93.9% [787/838] SVR12 when absent, 39.0% [55/141] SVR12 when present), with comparable reductions observed in Asians and non-Asians and across all categories of treatment experience, age, and cirrhosis. RAP-associated SVR12 rates declined with increasing baseline HCV RNA (SVR12 with RAPs: 64.7% [11/17] at 5-6 log10 IU/mL, 29.8% [14/47] at 7-8 log10). Without baseline RAPs, very high SVR12 rates (92-100%) were observed in older patients and patients with cirrhosis irrespective of national origin, with similarly high rates observed among treatment-naïve and interferon-experienced patients and those with high baseline HCV RNA. CONCLUSIONS: Following DCV + ASV treatment, the SVR12 rates in GT-1b patients without baseline NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were very high (approximately 90-100%), irrespective of age, cirrhosis, prior interferon treatment, or baseline HCV RNA. FUNDING: Bristol-Myers Squibb.
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Yonsei Authors
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
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