SCH 503034, a Novel Hepatitis C Virus Protease Inhibitor, Plus Pegylated Interferon α-2b for Genotype 1 Nonresponders

Sarrazin, Christoph; Rouzier, Roman; Wagner, Frank; Forestier, Nicole; Larrey, Dominique; Gupta, Samir K.; Hussain, Musaddeq; Shah, Amrik; Cutler, David L.; Zhang, Jenny; Zeuzem, Stefan

doi:10.1053/j.gastro.2007.01.041

Cited by 297 publications

(217 citation statements)

References 22 publications

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“…At the meta-analysis of results from the previous studies (Figure 2), the two viral strains were shown to respond equally well to Peg-IFN and RIBA, with a pooled OR of 0.98 (CI 0.72-1.32). This observation would signify that the different outcome between the two subtypes noted following triple therapy with Peg-IFN and RIBA in combination with a direct-acting agent (27,28) needs to be ascribed to the protease inhibitor administered, and not to Peg-IFN nor to RIBA.…”

Section: Discussionmentioning

confidence: 99%

“…Up to now, genotyping for HCV-1 subtypes will not impact on the day-to-day clinical management of chronic HCV infection, whereas conflicting reports exist on their influence on the outcome following conventional therapy with Peg-IFN and RIBA (6)(7)(8)(9)(10)(11)(12)(13). Recently, several HCV inhibitors appear to have selective activity against HCV 1 subtypes both in vitro and in vivo, with subtype 1a appearing more resistance-prone and less responsive to triple therapy than subtype 1b (25)(26)(27)(28)). …”

Section: Discussionmentioning

confidence: 99%

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HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome

Andriulli

Morisco²,

Ippolito

et al. 2014

Hepatol Int

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Short title: HCV subtypes 1a and 1b and treatment outcome after peg-interferon and ribavirin Key words: HCV genotype, HCV subtypes, chronic HCV liver disease, sustained virologic response, peg-interferon and ribavirin. Abstract words count: 254Full text words count: Tables # 2 o3 Figures # 2 Conclusion: in Italy HCV-1 subtype 1a prevails in young, male patients with less advanced liver damage, findings which imply a more recent spreading of the infection with this viral strain. The two HCV-1 subtypes appear equally responsive to Peg-IFN/RIBA, with IL28B genotyping and monitoring of RVR mostly influencing the therapeutic response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome

Andriulli

Morisco²,

Ippolito

et al. 2014

Hepatol Int

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“…Therefore, amantadine has no relevance in the antiviral treatment of chronic hepatitis C. Currently, direct antiviral agents such as inhibitors of the HCV serine protease and the RNA-dependent RNA polymerase are under clinical investigations, and initial phase I/II trials have shown that the combination of PEG IFN-␣ and ribavirin together with a direct antiviral compound can increase sustained virological response rates in genotype HCV-1-infected patients. [33][34][35][36][37] …”

Section: Discussionmentioning

confidence: 99%

Placebo-controlled trial of 400 mg amantadine combined with peginterferon alfa-2a and ribavirin for 48 weeks in chronic hepatitis C virus-1 infection

Wagner¹,

Hofmann²,

Teuber³

et al. 2008

Hepatology

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The impact of amantadine on virologic response rates of interferon-based treatment of chronic hepatitis C is controversial. The aim of this study was to compare virological response rates in patients with chronic hepatitis C virus (HCV)-1 infection treated with 400 mg amantadine or placebo in combination with peginterferon alfa-2a (40 kD) and ribavirin for 48 weeks. Seven hundred four previously untreated chronically HCV-1-infected patients (mean age, 46 ؎ 12 years) were randomized to (A) amantadine-sulphate (400 mg/day) (n ‫؍‬ 352) or (B) placebo (n ‫؍‬ 352), both in combination with 180 g peginterferon alfa-2a once weekly and ribavirin (1000-1200 mg/day) for 48 weeks. End of treatment and sustained virological response after a 24-week follow-up period were assessed by qualitative reverse transcription polymerase chain reaction (RT-PCR) (sensitivity, 50 IU/mL). Demographic and baseline virological parameters were similar in both treatment groups. In groups A and B, 231 of 352 patients (66%) and 256 of 352 patients (72%) achieved an end of treatment response, and 171 of 352 patients (49 %) and 186 of 352 patients (53 %) a sustained virological response, respectively. On-treatment dropout rate in the amantadine group was significantly higher than in the placebo group (32% versus 23%; P ‫؍‬ 0.01). However, adverse events and laboratory abnormalities were similar between both groups. Per-protocol analysis revealed similar sustained virological response rates in both treatment groups (53% versus 55%). Conclusion: In this large placebo-controlled multicenter study, amantadine even at a dose of 400 mg/day did not improve virological response rates of peginterferon alfa-2a and ribavirin in patients with chronic genotype HCV-1 infection. (HEPATOLOGY 2008;

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“…While it is possible to achieve this outcome with SOC, only approximately 40% to 50% of patients infected with genotype 1 HCV are successful (4,5,12). boceprevir Phase 1 and phase 2 trials established the efficacy and optimal dosing of boceprevir in combination with pegIFN and ribavirin for both treatment-naive and treatment-experienced patients (13,14). Interestingly, the use of a four-week lead-in phase with SOC before initiating boceprevir achieved greater response rates in treatmentnaive patients in the Serine Protease Inhibitor Therapy 1 (SPRINT-1) trial (14).…”

Section: Efficacymentioning

confidence: 99%

Review of Boceprevir and Telaprevir for the Treatment of Chronic Hepatitis C

Wilby

Partovi

Ford

et al. 2012

Canadian Journal of Gastroenterology

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OBJECTIVE: To summarize and evaluate the published literature pertaining to boceprevir and telaprevir, and to provide clinicians with suggestions for use in patients with chronic hepatitis C infection.METHODS: A standardized search strategy was performed using the MEDLINE, EMBASE, Google Scholar and International Pharmaceuticals Abstracts databases using the search terms “boceprevir”, “telaprevir”, “boceprevir and hepatitis C” and “telaprevir and hepatitis C”. A manual search of references was performed to identify articles missed by the electronic search. Studies were included in the review if they assessed either boceprevir or telaprevir in comparison with standard of care in chronic hepatitis C patients.RESULTS: The studies identified assessed boceprevir and telaprevir in genotype-1 hepatitis C patients. In both treatment-naive and treatment-experienced patients, sustained virological response rates were achieved more often with boceprevir or telaprevir in combination with pegylated interferon and ribavirin compared with pegylated interferon and ribavirin alone. Both medications were well tolerated, with anemia presenting as the most treatment-limiting adverse effect.CONCLUSIONS: Boceprevir and telaprevir will revolutionize the management of hepatitis C genotype 1 patients and will most likely decrease the burden of end-stage disease worldwide. However, current clinical limitations include establishing appropriate and cost-effective treatment durations, and use in special populations such as transplant patients and patients coinfected with HIV. Future research will need to clarify these clinical obstacles to clearly define the role of these agents in hepatitis C management.

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SCH 503034, a Novel Hepatitis C Virus Protease Inhibitor, Plus Pegylated Interferon α-2b for Genotype 1 Nonresponders

Cited by 297 publications

References 22 publications

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome

Placebo-controlled trial of 400 mg amantadine combined with peginterferon alfa-2a and ribavirin for 48 weeks in chronic hepatitis C virus-1 infection

Review of Boceprevir and Telaprevir for the Treatment of Chronic Hepatitis C

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