Effectiveness and safety of daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: Systematic review and meta‐analysis

Wang, Hui-Lian; Lu, Xi; Yang, Xudong; Xu, Nan

doi:10.1111/jgh.13587

Cited by 23 publications

(21 citation statements)

References 37 publications

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“…Two meta‐analysis have been reported regarding the correlation between HCV‐RNA levels and treatment response of this regimen. Wang et al showed that patients with a viral load of <8 × 10 5 had a tendency to have higher SVR rate compared with patients with a viral load of ≧8 × 10 5 . In contrast, Kao et al showed no difference between patients with a viral load of <3 × 10 6 and ≧3 × 10 6 ; the cutoff level in the latter study was almost the same as those of the present study …”

Section: Discussionsupporting

confidence: 54%

“…Wang et al 27 showed that patients with a viral load of <8 × 10 5 had a tendency to have higher SVR rate compared with patients with a viral load of ≧8 × 10 5 . 27 In contrast, Kao et al 28 showed no difference between patients with a viral load of <3 × 10 6 and ≧3 × 10 6 ; the cutoff level in the latter study was almost the same as those of the present study. 28 RVR has also been identified as a predictive on-treatment factor of SVR12.…”

Section: Discussionmentioning

confidence: 99%

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Daclatasvir and asunaprevir treatment in patients infected by genotype 1b of hepatitis C virus with no or subtle resistant associated substitutions (RAS) in NS5A‐Y93

Ishigami

Hayashi

Honda

et al. 2017

Journal of Medical Virology

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In this study, we investigated the real-world data of the first approved interferon-free regimen in Japan, daclatasvir and asunaprevir (DCV+ASV), in chronic hepatitis C patients infected HCV genotype 1b with no or subtle amount of baseline resistant associated substitutions (RAS). Among 924 patients registered in our multicenter study, 750 patients who were proven not to be infected with NS5A-Y93H RAS by direct sequencing and to have no or subtle amount (less than 20%) of NS5A-Y93H RAS by probe assays (Cycleave or PCR invader assay) were included in this study. We investigated the anti-viral effect and factors associated with SVR12. In statistical analysis, P < 0.05 was considered as significant. The SVR12 rate in this population was 92.1% (562/618). Factors associated with SVR12 were male (odds ratio: 2.128; 95%CI: 1.134-4.000, P = 0.019); lower serum γGTP (odds ratio: 1.007; 95%CI: 1.002-1.012, P = 0.006); lower HCV-RNA (odds ratio: 1.848; 95%CI: 1.087-3.145, P = 0.023), and RVR (odds ratio: 6.250; 95%CI: 2.445-15.873, P < 0.001). No patients with γGTP ≧ 80 IU/L without RVR showed SVR12 (0/4, 0%) and one patients with γGTP ≧ 20-< 80 IU/L and HCV-RNA ≧ 6.5 logIU/mL without RVR (5/10, 50%) and two female patients with RVR but γGTP ≧ 80 IU/L and HCV-RNA ≧ 6.5 logIU/mL (7/13, 53.8%) showed a low SVR12 rate. In the present study, we showed a good viral response with DCV-ASV treatment and identified four predictive factors associated with SVR12. These four markers could be a good predictive markers for the viral effect of this treatment regimen in patients with no or subtle amount of RAS in NS5A-Y93.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Daclatasvir and asunaprevir treatment in patients infected by genotype 1b of hepatitis C virus with no or subtle resistant associated substitutions (RAS) in NS5A‐Y93

Ishigami

Hayashi

Honda

et al. 2017

Journal of Medical Virology

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“…The SVR rate in PP analysis (95.8%), which excluded those who discontinued the combination therapy due to nonmedical reasons, was higher in previously published studies . Notably, the treatment withdrawal rate in treatment‐experienced patients was very low (2/162, 1.2%), so that the SVR rate in those patients was not inferior to treatment‐naive patients.…”

Section: Discussionmentioning

confidence: 77%

“…This may be attributable to the Korean practice under Government insurance system requiring mandatory pretreatment testing for RAS. Because the SVR rate in RAS‐negative patients was consistently higher than those with RAS (usually <70%) in previous studies, recent post‐2016 real‐world studies from Korea did not include RAS‐positive patients, resulting in a more favorable treatment response rate compared with former studies …”

Section: Discussionmentioning

confidence: 96%

“…Moreover, Sezaki et al showed that the SVR rate in those who met the inclusion criteria for clinical trials (87%) was comparable to those who did not meet the criteria (86.7%) by the real‐life study. A meta‐analysis, including nine studies published before May 2016, had reported SVR rates of 89.9%, 84.7%, and 81.9% in treatment‐naive patients, interferon‐ineligible/intolerable patients, and nonresponders. Nonetheless, several recent real‐world studies from Korea showed higher SVR rates (91.5%‐94.7%) in treatment‐experienced populations, which is in line with our findings.…”

Section: Discussionmentioning

confidence: 99%

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Real‐life effectiveness and safety of the daclatasvir/asunaprevir combination therapy for genotype 1b chronic hepatitis C patients: An emphasis on the pretreatment NS5A resistance‐associated substitution test

Jang

Kim

et al. 2019

Journal of Medical Virology

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This study aimed to investigate the real‐life effectiveness and safety of daclatasvir (DCV) and asunaprevir (ASV) combination therapy in Korean patients. We consecutively enrolled patients with genotype 1b hepatitis C virus (HCV) infection treated with at least one dose of DCV/ASV combination therapy in seven tertiary hospitals of South Korea. The sustained virologic response (SVR) rates and safety according to intention‐to‐treat (ITT) and per‐protocol (PP) analyses were evaluated. Among the 526 enrolled patients, 91% showed negative (87%) or “undetermined” (4%) resistance‐associated substitution (RAS); 9% did not undergo RAS testing. The SVR rates for ITT and PP were 89.3% and 95.0% in treatment‐naive patients and 93.2% and 95.6% in treatment‐experienced patients, respectively. In PP analysis, negative RAS was associated with higher SVR (96.3%) than with “undetermined RAS” (85.7%) or “not tested for RAS” (84.4%). Adverse events were reported in 185 (35.4%) patients, and events leading to discontinuation were observed in 4.3% of the study population. Forty‐two (8.0%) patients developed transaminase elevation (≥2 × upper normal limit), resulting in treatment discontinuation in six (1.1%) patients. DCV/ASV combination therapy showed acceptable efficacy in genotype 1b compensated HCV‐infected patients with negative pretreatment RAS. Although most adverse events were tolerable to continue antiviral treatment, adequate monitoring for transaminase elevation is warranted.

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The Discovery and Development of Daclatasvir: An Inhibitor of the Hepatitis C Virus NS5A Replication Complex

Meanwell

Belema

2019

Topics in Medicinal Chemistry

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The discovery of the hepatitis C virus (HCV) NS5A replication inhibitor daclatasvir (1) had its origins in a phenotypic screening lead. However, during the optimization campaign, it was observed that some members of the chemotype underwent a radical dimerization under the assay conditions. This redirected the effort to focus on palindromic molecules, a species subsequently shown to complement the dimeric nature of the NS5A protein. The most challenging aspect of the discovery program was extending antiviral activity to encompass GT-1a virus which was accomplished only after the development of extensive structure-activity relationships. In clinical trials, oral administration of daclatasvir (1) produced a profound effect on viral load with onset that was more rapid than had been seen previously with either NS3 protease or NS5B polymerase inhibitors. A groundbreaking clinical trial that combined daclatasvir (1) with the protease inhibitor asunaprevir (52) established that a chronic HCV infection could be cured with small molecule therapy in the absence of immune stimulation, setting the stage for approval of this regimen for the treatment of GT-1b-infected subjects by the Japanese health authorities on July 4, 2014.

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Effectiveness and safety of daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: Systematic review and meta‐analysis

Abstract: Daclatasvir plus asunaprevir provides a highly effective and well-tolerated treatment option for patients with HCV genotype 1b. However, patients with nonstructural protein 5A RAVs at baseline should be assessed to optimize more potent direct antiviral agent therapies.

Cited by 23 publications

References 37 publications

Daclatasvir and asunaprevir treatment in patients infected by genotype 1b of hepatitis C virus with no or subtle resistant associated substitutions (RAS) in NS5A‐Y93

Daclatasvir and asunaprevir treatment in patients infected by genotype 1b of hepatitis C virus with no or subtle resistant associated substitutions (RAS) in NS5A‐Y93

Real‐life effectiveness and safety of the daclatasvir/asunaprevir combination therapy for genotype 1b chronic hepatitis C patients: An emphasis on the pretreatment NS5A resistance‐associated substitution test

The Discovery and Development of Daclatasvir: An Inhibitor of the Hepatitis C Virus NS5A Replication Complex

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