Limits...
New treatments for genotype 1 chronic hepatitis C - focus on simeprevir.

Kanda T, Nakamoto S, Wu S, Yokosuka O - Ther Clin Risk Manag (2014)

Bottom Line: Chronic hepatitis C virus (HCV) infection causes end-stage liver diseases and hepato cellular carcinoma.In the USA, Canada, and Japan, simeprevir - one of the second-generation HCV NS3/4A protease inhibitors - in combination with peginterferon α-2a or 2b plus ribavirin has recently been approved for HCV genotype 1-infected patients and is now used in daily clinical practice.In the near future, the development of interferon-free regimens with simeprevir is expected.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

ABSTRACT
Chronic hepatitis C virus (HCV) infection causes end-stage liver diseases and hepato cellular carcinoma. In the USA, Canada, and Japan, simeprevir - one of the second-generation HCV NS3/4A protease inhibitors - in combination with peginterferon α-2a or 2b plus ribavirin has recently been approved for HCV genotype 1-infected patients and is now used in daily clinical practice. This review summarizes the mechanism of action of simeprevir and the results of clinical trials of simeprevir and peginterferon plus ribavirin for HCV genotype 1 patients. In general, the simeprevir and peginterferon plus ribavirin treatment is highly effective and its adverse events are similar to those of peginterferon plus ribavirin only, the exception being milder, reversible jaundice. In the near future, the development of interferon-free regimens with simeprevir is expected. Careful attention should be paid to new results of clinical trials with simeprevir.

No MeSH data available.


Related in: MedlinePlus

PILLAR study design and results. SVR rates were measured at 24 weeks after the end of treatment.Notes: RGT algorithm: all therapy of the SMV group was completed at week 24 if hepatitis C virus RNA was <25 IU/mL at week 4 and undetectable at weeks 12, 16, and 20. Data from Fried MW et al.21 In the control group, patients received PR (180 μg/week peginterferon; 1,000–1,200 mg/day ribavirin) for 48 weeks.Abbreviations: PILLAR, Protease Inhibitor TMC435 Trial Assessing the Optimal Dose and Duration as Once-Daily Antiviral Regimen; PR, peginterferon plus ribavirin; RGT, response-guided therapy; SMV, simeprevir; SVR, sustained virologic response.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4043814&req=5

f2-tcrm-10-387: PILLAR study design and results. SVR rates were measured at 24 weeks after the end of treatment.Notes: RGT algorithm: all therapy of the SMV group was completed at week 24 if hepatitis C virus RNA was <25 IU/mL at week 4 and undetectable at weeks 12, 16, and 20. Data from Fried MW et al.21 In the control group, patients received PR (180 μg/week peginterferon; 1,000–1,200 mg/day ribavirin) for 48 weeks.Abbreviations: PILLAR, Protease Inhibitor TMC435 Trial Assessing the Optimal Dose and Duration as Once-Daily Antiviral Regimen; PR, peginterferon plus ribavirin; RGT, response-guided therapy; SMV, simeprevir; SVR, sustained virologic response.

Mentions: The Phase IIb, double-blind, placebo-controlled PILLAR trial (A Phase II Study of TMC435 in Combination with Peginterferon α-2a and Ribavirin in Patients Infected with Genotype 1 HCV Who Never Received Treatment; NCT00882908) examined the efficacy and safety of two different doses of simeprevir administered once daily (QD) for two different durations in combination with peginterferon plus ribavirin in treatment-naïve HCV genotype 1 patients.21 A total of 386 patients were randomly assigned to one of five groups (Figure 2): simeprevir (75 mg or 150 mg QD) for 12 or 24 weeks, or placebo, and peginterferon plus ribavirin. Patients in the simeprevir arms were treated for 24 or 48 weeks according to response-guided therapy (RGT) criteria. SVR rates, measured at 24 weeks after the end of treatment for each treatment group, are shown in Figure 2. SVR rates were 74.7%–86.1% in the simeprevir groups versus 64.9% in the placebo control group (P<0.05).21 For patients treated with simeprevir 75 mg, the SVR rates were lower for genotype 1a (66.2%) than for genotype 1b (88.9%), although the SVR rates in genotype 1a (82.4%) and 1b (83.8%) patients were similar with simeprevir 150 mg.21 For the 332 patients with METAVIR scores of F0–F2, SVR rates were 81.7% with simeprevir 75 mg, 84.6% with simeprevir 150 mg, and 64.3% with placebo control. For the 53 patients with METAVIR scores of F3, SVR rates were 63.0% with simeprevir 75 mg, 75.0% with simeprevir 150 mg, and 71.4% with placebo control. Multiple regression analysis showed that treatment with simeprevir was associated with higher rates of SVR.21


New treatments for genotype 1 chronic hepatitis C - focus on simeprevir.

Kanda T, Nakamoto S, Wu S, Yokosuka O - Ther Clin Risk Manag (2014)

PILLAR study design and results. SVR rates were measured at 24 weeks after the end of treatment.Notes: RGT algorithm: all therapy of the SMV group was completed at week 24 if hepatitis C virus RNA was <25 IU/mL at week 4 and undetectable at weeks 12, 16, and 20. Data from Fried MW et al.21 In the control group, patients received PR (180 μg/week peginterferon; 1,000–1,200 mg/day ribavirin) for 48 weeks.Abbreviations: PILLAR, Protease Inhibitor TMC435 Trial Assessing the Optimal Dose and Duration as Once-Daily Antiviral Regimen; PR, peginterferon plus ribavirin; RGT, response-guided therapy; SMV, simeprevir; SVR, sustained virologic response.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043814&req=5

f2-tcrm-10-387: PILLAR study design and results. SVR rates were measured at 24 weeks after the end of treatment.Notes: RGT algorithm: all therapy of the SMV group was completed at week 24 if hepatitis C virus RNA was <25 IU/mL at week 4 and undetectable at weeks 12, 16, and 20. Data from Fried MW et al.21 In the control group, patients received PR (180 μg/week peginterferon; 1,000–1,200 mg/day ribavirin) for 48 weeks.Abbreviations: PILLAR, Protease Inhibitor TMC435 Trial Assessing the Optimal Dose and Duration as Once-Daily Antiviral Regimen; PR, peginterferon plus ribavirin; RGT, response-guided therapy; SMV, simeprevir; SVR, sustained virologic response.
Mentions: The Phase IIb, double-blind, placebo-controlled PILLAR trial (A Phase II Study of TMC435 in Combination with Peginterferon α-2a and Ribavirin in Patients Infected with Genotype 1 HCV Who Never Received Treatment; NCT00882908) examined the efficacy and safety of two different doses of simeprevir administered once daily (QD) for two different durations in combination with peginterferon plus ribavirin in treatment-naïve HCV genotype 1 patients.21 A total of 386 patients were randomly assigned to one of five groups (Figure 2): simeprevir (75 mg or 150 mg QD) for 12 or 24 weeks, or placebo, and peginterferon plus ribavirin. Patients in the simeprevir arms were treated for 24 or 48 weeks according to response-guided therapy (RGT) criteria. SVR rates, measured at 24 weeks after the end of treatment for each treatment group, are shown in Figure 2. SVR rates were 74.7%–86.1% in the simeprevir groups versus 64.9% in the placebo control group (P<0.05).21 For patients treated with simeprevir 75 mg, the SVR rates were lower for genotype 1a (66.2%) than for genotype 1b (88.9%), although the SVR rates in genotype 1a (82.4%) and 1b (83.8%) patients were similar with simeprevir 150 mg.21 For the 332 patients with METAVIR scores of F0–F2, SVR rates were 81.7% with simeprevir 75 mg, 84.6% with simeprevir 150 mg, and 64.3% with placebo control. For the 53 patients with METAVIR scores of F3, SVR rates were 63.0% with simeprevir 75 mg, 75.0% with simeprevir 150 mg, and 71.4% with placebo control. Multiple regression analysis showed that treatment with simeprevir was associated with higher rates of SVR.21

Bottom Line: Chronic hepatitis C virus (HCV) infection causes end-stage liver diseases and hepato cellular carcinoma.In the USA, Canada, and Japan, simeprevir - one of the second-generation HCV NS3/4A protease inhibitors - in combination with peginterferon α-2a or 2b plus ribavirin has recently been approved for HCV genotype 1-infected patients and is now used in daily clinical practice.In the near future, the development of interferon-free regimens with simeprevir is expected.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

ABSTRACT
Chronic hepatitis C virus (HCV) infection causes end-stage liver diseases and hepato cellular carcinoma. In the USA, Canada, and Japan, simeprevir - one of the second-generation HCV NS3/4A protease inhibitors - in combination with peginterferon α-2a or 2b plus ribavirin has recently been approved for HCV genotype 1-infected patients and is now used in daily clinical practice. This review summarizes the mechanism of action of simeprevir and the results of clinical trials of simeprevir and peginterferon plus ribavirin for HCV genotype 1 patients. In general, the simeprevir and peginterferon plus ribavirin treatment is highly effective and its adverse events are similar to those of peginterferon plus ribavirin only, the exception being milder, reversible jaundice. In the near future, the development of interferon-free regimens with simeprevir is expected. Careful attention should be paid to new results of clinical trials with simeprevir.

No MeSH data available.


Related in: MedlinePlus