Rapid Decline of Viral RNA in Hepatitis C Patients Treated With VX-950: A Phase Ib, Placebo-Controlled, Randomized Study

Reesink, H. W.; Zeuzem, Stefan; Weegink, Christine J.; Forestier, Nicole; Vliet, André van; Rooij, Jeroen van de Wetering de; McNair, Lindsay; Purdy, S.; Kauffman, Robert S.; Alam, John; Jansen, Petér L. M.

doi:10.1053/j.gastro.2006.07.013

Cited by 368 publications

(301 citation statements)

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“…13 Analysis of the HCV NS3 protease domain sequence from patients in a previous clinical study of telaprevir monotherapy showed that viral rebound during the 14-day treatment period was associated with the presence of viral variants with reduced sensitivity to telaprevir. 4 Consistent with these findings, the viral rebound observed in patients who received telaprevir alone in the present study was associated with the selection of similar variants. In HCV replicon studies, these viral variants remained sensitive to interferon.…”

Section: Discussionsupporting

confidence: 90%

“…3 In a 14-day clinical trial in patients with genotype 1 chronic hepatitis C, telaprevir was well tolerated and showed substantial antiviral effects. 4 HCV RNA levels decreased by at least 2 log 10 in all 28 patients treated with telaprevir. In the 750-mg dose group, which had the highest trough plasma concentrations of telaprevir, the median reduction in HCV RNA was 4.4 log 10 , and 2 patients had undetectable HCV RNA levels.…”

mentioning

confidence: 88%

“…Some patients treated with telaprevir had viral breakthrough during the 14-day dosing period. 4 Analysis of the NS3 protease sequence suggested that the breakthrough was related to selection of viral variants with decreased sensitivity to telaprevir. 4 Unlike the specifically targeted antiviral activity of telaprevir, the activity of interferon against HCV is due to the stimulation of hundreds of genes that result in nonspecific antiviral and immunomodulatory effects (reviewed in Feld and Hoofnagle 5 ).…”

mentioning

confidence: 99%

“…4 Analysis of the NS3 protease sequence suggested that the breakthrough was related to selection of viral variants with decreased sensitivity to telaprevir. 4 Unlike the specifically targeted antiviral activity of telaprevir, the activity of interferon against HCV is due to the stimulation of hundreds of genes that result in nonspecific antiviral and immunomodulatory effects (reviewed in Feld and Hoofnagle 5 ). When given as monotherapy, peginterferon alfa has limited efficacy against chronic hepatitis C. 6,7 In HCV replicon studies, interferon and telaprevir had synergistic effects in reducing HCV RNA, 8 and viral variants with decreased sensitivity to telaprevir remained sensitive to interferon.…”

mentioning

confidence: 99%

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Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C

et al. 2007

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 88%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C

et al. 2007

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“…Five factors associated with achieving an SVR were: assignment to a boceprevir group; previous relapse versus nonresponse; low viral load at baseline; absence of cirrhosis; and >1 log 10 IU/mL decrease in HCV RNA levels at week 4 (18). telaprevir Phase 1 and phase 2 trials established efficacy in a daily dosage regimen of 750 mg three times a day of telaprevir in both treatment-naive and treatment-experienced patients (19)(20)(21)(22)(23)(24)(25). Because pegIFN and ribavirin are associated with many dose-and duration-limiting adverse events, phase 2 trials assessed whether telaprevir could be combined with pegIFN alone without coadministration of ribavirin.…”

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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