1399 12-Week Interferon-Free Regimen of Abt-450/R +Abt-333 +Ribavirin Achieved Svr12 in More Than 90% of Treatment-Naive HCV Genotype-1-Infected Subjects and 47% of Previous Non-Responders

Poordad, F.; Läwitz, E.; Kowdley, K.V.; Everson, Gregory T.; Freilich, B.; Cohen, Daniel E.; Siggelkow, Sara; Heckaman, Michele; Menon, Rajeev; Matias, T; Podsadecki, Thomas; Bernstein, Barry

doi:10.1016/s0168-8278(12)61410-x

Cited by 57 publications

(41 citation statements)

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“…In the setting of direct acting antiviral (DAA) regimens, the rs12979860 CC variant was associated with favorable outcome following triple therapy with the first generation protease inhibitors, telaprevir and boceprevir [20,21], but with the introduction of interferon-free regimens the importance of the IL28B genetic variants appears to be diminishing [22]. Although, in one interferon-sparing trial among HCV genotype 1 infected patients evaluating faldaprevir and deleobuvir, with and without ribavirin, the CC variant of rs12979860 was associated with increased likelihood of achieving SVR in comparison with non-CC variants [23].…”

Section: Il28b Genetic Variants and Impact On Direct Acting Antiviral-bmentioning

confidence: 99%

Impact of IL28B, ITPA and PNPLA3 Genetic Variants on Therapeutic Outcome and Progression of Hepatitis C Virus Infection

Rembeck

Lagging

2015

Pharmacogenomics

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Chronic HCV infection comprises a broad spectrum of liver disease, ranging from no or minimal activity to active hepatitis that in time may progress to severe liver fibrosis, cirrhosis and hepatocellular carcinoma if left untreated. This review describes the impact of genetic variants of interleukin 28B (IL28B; also known as interferon-lambda 3), inosine triphosphate pyrophosphatase (ITPA) and patatin-like phospholipase domain-containing 3 (PNPLA3) on therapeutic outcome and liver disease severity in HCV-infected patients.

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Section: Il28b Genetic Variants and Impact On Direct Acting Antiviral-bmentioning

confidence: 99%

Impact of IL28B, ITPA and PNPLA3 Genetic Variants on Therapeutic Outcome and Progression of Hepatitis C Virus Infection

Rembeck

Lagging

2015

Pharmacogenomics

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“…An overview of the efficacy and tolerability of DAA combination treatments with or without PEG-IFN is outlined in Table 3 [ Gane et al 2010aFeld et al 2012;Zeuzem et al 2010Zeuzem et al , 2011Zeuzem et al , 2012bZeuzem et al , 2012cJacobson et al 2012;Poordad et al 2012c;Lawitz et al 2012c;Lok et al 2012aLok et al , 2012bChayama et al 2012;Kowdley et al 2013b;Sulkowski et al 2012aSulkowski et al , 2012bEverson et al 2012Everson et al , 2013.…”

Section: Htas and Other Antiviral Treatmentsmentioning

confidence: 99%

An update on the treatment of genotype-1 chronic hepatitis C infection: lessons from recent clinical trials

Wendt

Bourlière

2013

Therapeutic Advances in Infection

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The launch of first-generation protease inhibitors (PIs) was a major step forward in hepatitis C virus (HCV) treatment. However, this major advance is, up to now, restricted to genotype-1 (GT-1) patients. However, the ongoing development of new direct-acting antiviral agents (DAAs) allows new hope for the future. The development of second-wave and second-generation PIs yields higher antiviral potency through plurigenotypic activity, more convenient daily administration, fewer side effects and, for the second-generation PIs, potential activity against resistance-associated variants. NS5B inhibitors (NS5B.I) include nucleoside/nucleotide inhibitors (NIs) and nonnucleotide inhibitors (NNIs). NIs have high efficacy across all genotypes. Sofosbuvir has highly potent antiviral activity across all genotypes in association with pegylated interferon (IFN) and ribavirin (PR), thus allowing shortened treatment duration. NS5A inhibitors (NS5A.I) have highly potent antiviral activity. It has recently been shown for the first time that NS5A.I in combination with PI can cure GT-1b null-responder patients in an IFN-free regimen. In addition, several studies demonstrate that IFN-free regimens with DAA combinations are able to cure a large number of either naïve or treatment-experienced GT-1 patients. Moreover, a quadruple regimen with PR is able to cure almost all GT-1 null-responders. The development of pan-genotypic DAAs (NIs or NS5A.I) allows new combinations with or without PR that increase the rate of sustained virological response (SVR) for all patients, even for those with cirrhosis and independently of the genotype. Therefore, the near future of HCV treatment looks promising. The purpose of this article is to provide an overview of the clinical results recently reported for HCV treatment in GT-1 patients.

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“…Two recent studies, conducted by investigators mostly from the same collaborative research group, which evaluated the efficacy of ABT-450/r (the NS3-NS4A inhibitor, ABT-450, administered in conjunction with ritonavir, a CYP3A4 inhibitor used in the treatment of HIV infection [35]) in combination with various other direct-acting antiviral agents in the treatment of patients with HCV infection, were also presented at ILC 2012 [43,44]. The first study, which evaluated the efficacy of a 12 week course of treatment with ABT-450/r in combination with both the NS5B non-nucleos(t)ide inhibitor, ABT-333, and ribavirin in 50 patients with HCV genotype 1, found that this particular combination of antiviral therapy resulted in an extremely high SVR 12 rate of around 95% in treatment-naïve subjects [44].…”

Section: Studies In Patients With Hcv Genotypementioning

confidence: 99%

“…The first study, which evaluated the efficacy of a 12 week course of treatment with ABT-450/r in combination with both the NS5B non-nucleos(t)ide inhibitor, ABT-333, and ribavirin in 50 patients with HCV genotype 1, found that this particular combination of antiviral therapy resulted in an extremely high SVR 12 rate of around 95% in treatment-naïve subjects [44]. This study, which also compared the efficacy of 2 treatment regimens (differing in the dosing of ABT-450/r) of the aforementioned combination of antiviral therapy, also found that there was no significant difference in the SVR rates observed in treatment-naïve subjects assigned to the different treatment regimens.…”

Section: Studies In Patients With Hcv Genotypementioning

confidence: 99%

Oral Direct-Acting Antiviral Therapy for Hepatitis C

Ho¹,

Ho²

2012

J Antivir Antiretrovir

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1399 12-Week Interferon-Free Regimen of Abt-450/R +Abt-333 +Ribavirin Achieved Svr12 in More Than 90% of Treatment-Naive HCV Genotype-1-Infected Subjects and 47% of Previous Non-Responders

Cited by 57 publications

References 0 publications

Impact of IL28B, ITPA and PNPLA3 Genetic Variants on Therapeutic Outcome and Progression of Hepatitis C Virus Infection

Impact of IL28B, ITPA and PNPLA3 Genetic Variants on Therapeutic Outcome and Progression of Hepatitis C Virus Infection

An update on the treatment of genotype-1 chronic hepatitis C infection: lessons from recent clinical trials

Oral Direct-Acting Antiviral Therapy for Hepatitis C

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