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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)637-649
Number of pages13
JournalAdvances in Therapy
Volume32
Issue number7
DOIs
Publication statusPublished - 2015 Jul 9

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Hepacivirus
Genotype
Fibrosis
RNA
Interferons
Therapeutics
BMS-790052
asunaprevir
Sustained Virologic Response
Chronic Hepatitis C
Korea
Protease Inhibitors
Japan

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

McPhee, Fiona ; Suzuki, Yoshiyuki ; Toyota, Joji ; Karino, Yoshiyasu ; Chayama, Kasuaki ; Kawakami, Yoshiiku ; Yu, Min Lung ; Ahn, Sang Hoon ; Ishikawa, Hiroki ; Bhore, Rafia ; Zhou, Nannan ; Hernandez, Dennis ; Mendez, Patricia ; Kumada, Hiromitsu. / High Sustained Virologic Response to Daclatasvir Plus Asunaprevir in Elderly and Cirrhotic Patients with Hepatitis C Virus Genotype 1b Without Baseline NS5A Polymorphisms. In: Advances in Therapy. 2015 ; Vol. 32, No. 7. pp. 637-649.
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abstract = "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-na{\"i}ve 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.",
author = "Fiona McPhee and Yoshiyuki Suzuki and Joji Toyota and Yoshiyasu Karino and Kasuaki Chayama and Yoshiiku Kawakami and Yu, {Min Lung} and Ahn, {Sang Hoon} and Hiroki Ishikawa and Rafia Bhore and Nannan Zhou and Dennis Hernandez and Patricia Mendez and Hiromitsu Kumada",
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McPhee, F, Suzuki, Y, Toyota, J, Karino, Y, Chayama, K, Kawakami, Y, Yu, ML, Ahn, SH, Ishikawa, H, Bhore, R, Zhou, N, Hernandez, D, Mendez, P & Kumada, H 2015, 'High Sustained Virologic Response to Daclatasvir Plus Asunaprevir in Elderly and Cirrhotic Patients with Hepatitis C Virus Genotype 1b Without Baseline NS5A Polymorphisms', Advances in Therapy, vol. 32, no. 7, pp. 637-649. https://doi.org/10.1007/s12325-015-0221-5

High Sustained Virologic Response to Daclatasvir Plus Asunaprevir in Elderly and Cirrhotic Patients with Hepatitis C Virus Genotype 1b Without Baseline NS5A Polymorphisms. / McPhee, Fiona; Suzuki, Yoshiyuki; Toyota, Joji; Karino, Yoshiyasu; Chayama, Kasuaki; Kawakami, Yoshiiku; Yu, Min Lung; Ahn, Sang Hoon; Ishikawa, Hiroki; Bhore, Rafia; Zhou, Nannan; Hernandez, Dennis; Mendez, Patricia; Kumada, Hiromitsu.

In: Advances in Therapy, Vol. 32, No. 7, 09.07.2015, p. 637-649.

Research output: Contribution to journalArticle

TY - JOUR

T1 - High Sustained Virologic Response to Daclatasvir Plus Asunaprevir in Elderly and Cirrhotic Patients with Hepatitis C Virus Genotype 1b Without Baseline NS5A Polymorphisms

AU - McPhee, Fiona

AU - Suzuki, Yoshiyuki

AU - Toyota, Joji

AU - Karino, Yoshiyasu

AU - Chayama, Kasuaki

AU - Kawakami, Yoshiiku

AU - Yu, Min Lung

AU - Ahn, Sang Hoon

AU - Ishikawa, Hiroki

AU - Bhore, Rafia

AU - Zhou, Nannan

AU - Hernandez, Dennis

AU - Mendez, Patricia

AU - Kumada, Hiromitsu

PY - 2015/7/9

Y1 - 2015/7/9

N2 - 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.

AB - 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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