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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.

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 - Adv Ther (2015)

Bottom Line: 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).Bristol-Myers Squibb.

View Article: PubMed Central - PubMed

Affiliation: Bristol-Myers Squibb Research and Development, Wallingford, CT, USA, fiona.mcphee@BMS.com.

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.

No MeSH data available.


Related in: MedlinePlus

SVR12 with versus without baseline NS5A polymorphisms. SVR12 12-week sustained virologic response
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Fig2: SVR12 with versus without baseline NS5A polymorphisms. SVR12 12-week sustained virologic response

Mentions: The association between baseline NS5A polymorphisms and SVR12 is shown in Fig. 2 for the full SVR12 population of 979 patients. Among all GT-1b-infected patients, the presence of the DCV NS5A RAPs L31F/I/M/V and/or Y93H at baseline was associated with reduced SVR12 following treatment with DCV + ASV (SVR12 range: 36.9–41.9%), while SVR12 rates in the absence of these RAPs were high (SVR12 range: 88.0–93.9%). By contrast, neither baseline L28 M nor R30Q had any relevant effect on SVR12 in the absence of NS5A polymorphisms at amino acids 31 or 93 (SVR12 approximately 86%).Fig. 2


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

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 - Adv Ther (2015)

SVR12 with versus without baseline NS5A polymorphisms. SVR12 12-week sustained virologic response
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4522028&req=5

Fig2: SVR12 with versus without baseline NS5A polymorphisms. SVR12 12-week sustained virologic response
Mentions: The association between baseline NS5A polymorphisms and SVR12 is shown in Fig. 2 for the full SVR12 population of 979 patients. Among all GT-1b-infected patients, the presence of the DCV NS5A RAPs L31F/I/M/V and/or Y93H at baseline was associated with reduced SVR12 following treatment with DCV + ASV (SVR12 range: 36.9–41.9%), while SVR12 rates in the absence of these RAPs were high (SVR12 range: 88.0–93.9%). By contrast, neither baseline L28 M nor R30Q had any relevant effect on SVR12 in the absence of NS5A polymorphisms at amino acids 31 or 93 (SVR12 approximately 86%).Fig. 2

Bottom Line: 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).Bristol-Myers Squibb.

View Article: PubMed Central - PubMed

Affiliation: Bristol-Myers Squibb Research and Development, Wallingford, CT, USA, fiona.mcphee@BMS.com.

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.

No MeSH data available.


Related in: MedlinePlus