Daclatasvir Combined with Peginterferon Alfa-2A and Ribavirin in Japanese Patients Infected with Hepatitis C Genotype 1

Izumi, Namiki; Yokosuka, Osamu; Kawada, Norifumi; Osaki, Yukio; Yamamoto, Kazuhide; Sata, Michio; Ishikawa, Hiroki; Ueki, Tomoko; Hu, Wenhua; McPhee, Fiona; Hughes, Eric; Kumada, Hiromitsu

doi:10.3851/imp2731

Cited by 26 publications

(26 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because susceptibility to IFN was not attenuated in patients with Y93H RAV, IFN‐based therapy, such as with the NS3 inhibitor simeprevir plus PEG IFN and RBV, may be preferable for these patients. It was shown recently that daclatasvir plus PEG IFN and RBV combination therapy achieved a high rate of SVR in treatment naive Japanese patients . Taking into account the high prevalence of NS5A RAV at baseline, as shown here, the result of this report suggested that RAV in NS5A may not impact the outcomes of IFN‐based therapies.…”

Section: Discussionsupporting

confidence: 50%

Naturally occurring, resistance‐associated hepatitis C virus NS5A variants are linked to interleukin‐28B genotype and are sensitive to interferon‐based therapy

Itakura

Kurosaki

Takada

et al. 2015

Hepatology Research

Self Cite

View full text Add to dashboard Cite

Aim:The presence of resistance-associated variants (RAV) may attenuate the efficacy of direct-acting antivirals (DAA) in combination therapy for hepatitis C. The aim of this study was to characterize the NS3 and NS5A regions of hepatitis C virus (HCV) in naturally occurring RAV. Methods:The NS3 and NS5A regions of HCV were amplified by nested polymerase chain reaction and their nucleotide sequences were determined by direct sequencing in 493 genotype 1b patients naive to DAA-based therapies. The effect of baseline RAV on response to pegylated interferon and ribavirin therapy was analyzed in 65 patients after stratification by interleukin (IL)-28B genotype.Results: The incidence of RAV was 7.9% in NS3 (V36I/L, 1.2%; T54S, 2.8%; Q80K/R, 3.0%; A156S, 0.2%; and D168E/T, 2.4%) and 20.2% in NS5A (L31I/M, 2.2%; and Y93H, 19.0%). The incidence in interferon experienced and naive patients was similar. The incidence of Y93H in NS5A was significantly higher in the IL-28B TT genotype (rs8099917) than non-TT (27.1% vs 9.5%, P < 0.001). The virological response to pegylated interferon plus ribavirin therapy was not affected by the presence of RAV in IL-28B TT genotype.Conclusion: RAV, especially Y93H in the NS5A region, were highly prevalent in DAA naive patients with genotype 1b HCV in Japan and were linked to IL-28B TT genotype. Interferonbased therapy could be an alternative for patients with RAV because these variants did not attenuate the response to that therapy. The analysis of RAV may impact the selection of the optimal treatment strategy.

show abstract

Section: Discussionsupporting

confidence: 50%

Naturally occurring, resistance‐associated hepatitis C virus NS5A variants are linked to interleukin‐28B genotype and are sensitive to interferon‐based therapy

Itakura

Kurosaki

Takada

et al. 2015

Hepatology Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Daclatasvir and asunaprevir plasma concentration‐time data were obtained from 4 clinical studies (AI444021, AI444022, AI447017, and AI447026) and 2 clinical studies (AI447017 and AI447026), respectively (Supplementary Table ). All clinical studies included in the popPK analyses were conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

Population Pharmacokinetic Analysis for Daclatasvir and Asunaprevir in Japanese Subjects With Chronic Hepatitis C Virus Infection

Osawa

Ueno

Ishikawa

et al. 2018

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

Daclatasvir is a nonstructural protein 5A replication complex inhibitor, and asunaprevir is a nonstructural protein 3 protease inhibitor for hepatitis C virus (HCV). In 2014, the combination therapy of daclatasvir and asunaprevir received the first global approval in Japan as the first nonribavirin, all‐oral therapy for HCV treatment. The population pharmacokinetics (popPK) of daclatasvir and asunaprevir were characterized by nonlinear mixed‐effects modeling using 3801 and 2626 concentration data from 336 and 265 Japanese HCV subjects, respectively. The plasma pharmacokinetic profiles of daclatasvir and asunaprevir were described by a 1‐compartment model. Parameter estimates (interindividual variability) of daclatasvir apparent clearance (CL/F) and apparent volume of the central compartment (V/F) were 5.29 L/h (39.4%) and 64.2 L (38.1%). The effects of all statistically significant covariates on daclatasvir PK parameters were within or overlapped the 80% to 125% boundaries, suggesting a lack of clinical relevance. Parameter estimates (interindividual variability) of asunaprevir CL/F and V/F were 52.1 L/h (41.5%) and 75.1 L (93.4%), respectively. Baseline and time‐varying aspartate aminotransferase (AST) and cirrhosis on CL/F and formulation (soft‐gel capsule or tablet) on F were included as significant covariates in the asunaprevir popPK model. The effects of all covariates exceeded the 80% to 125% boundaries, indicating that the asunaprevir soft‐gel capsule had higher bioavailability than the tablet and that asunaprevir exposure increased with cirrhosis and increasing baseline and time‐varying AST values. The popPK models adequately described the PK profiles of daclatasvir and asunaprevir in Japanese HCV subjects.

show abstract

“…In another study, TN patients (n = 8) and prior non-responders (n = 9) were treated with DCV (60 mg) and PEG-IFN alpha for 24 or 48 weeks based on the PDR. A 24-week SVR was achieved in all the TN patients and 7 of the 9 prior non-responders (48). Because treatment was continued based on PDR for 24 or 48 weeks in these studies, we were unable to determine the 12-week SVR rate for treatment with PEG-IFN alpha/DCV, and therefore, we did not include these studies in our meta-analysis.…”

Section: Resultsmentioning

confidence: 97%

Daclatasvir-based Treatment Regimens for Hepatitis C Virus Infection: A Systematic Review and Meta-Analysis

Alavian

Rezaee‐Zavareh

2016

Hepat Mon

View full text Add to dashboard Cite

ContextDirect acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus (HCV) infection, which is a major public health problem. Among the known DAAs, daclatasvir (DCV), an inhibitor of the non-structural 5A protein, has been used in combination with several drugs for treatment of infection with HCV of different genotypes under different conditions. We conducted a systematic review and meta-analysis of combination therapy with DCV.Evidence AcquisitionWe performed a systematic search in PubMed, Scopus, Science Direct and Web of Science with appropriate keywords for DCV. Studies that evaluated any regimen containing DCV and reported the sustained virological response (SVR) 12 weeks after therapy based on the HCV genotype, treatment duration and use of ribavirin (RBV) were included. The selected studies were considered for meta-analysis using STATA 11.0.ResultsWe found six different regimens containing DCV: DCV/asunaprevir (ASV), DCV/ASV/beclubavir, DCV/pegylated interferon lambda or alpha/RBV with or without ASV, DCV/simeprevir, DCV/VX-135 and DCV/sofosbuvir (SOF). Most of these regimens were used for the treatment of HCV genotype 1 infections, and in most cases, treatment failure was noted in subtype 1a infections. Among all these regimens, DCV/SOF with or without RBV for 12 or 24 weeks was found to be an efficacious approach for treatment of different types of patients with infections with different HCV genotypes.ConclusionsAmong the treatment regimens containing DCV, DCV/SOF has the highest SVR rate for the treatment of infection with different HCV genotypes in different patient contexts; thus, this regimen shows promise for the treatment of HCV infections.

show abstract

Daclatasvir Combined with Peginterferon Alfa-2A and Ribavirin in Japanese Patients Infected with Hepatitis C Genotype 1

Cited by 26 publications

References 21 publications

Naturally occurring, resistance‐associated hepatitis C virus NS5A variants are linked to interleukin‐28B genotype and are sensitive to interferon‐based therapy

Naturally occurring, resistance‐associated hepatitis C virus NS5A variants are linked to interleukin‐28B genotype and are sensitive to interferon‐based therapy

Population Pharmacokinetic Analysis for Daclatasvir and Asunaprevir in Japanese Subjects With Chronic Hepatitis C Virus Infection

Daclatasvir-based Treatment Regimens for Hepatitis C Virus Infection: A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About