Predictive factors for 24 weeks sustained virologic response (SVR24) and viral relapse in patients treated with simeprevir plus peginterferon and ribavirin

Hepatol Int. 2016 Jan;10(1):158-68. doi: 10.1007/s12072-015-9654-9. Epub 2015 Aug 12.

Abstract

Background: Simeprevir with peginterferon and ribavirin has been used for the treatment of chronic hepatitis caused by genotype 1 hepatitis C virus (HCV). We explored the predictive factors for sustained virological response (SVR) and viral relapse using datasets from four Japanese phase 3 studies (CONCERTO).

Methods: We used a multiple logistic regression model. First, an integrated dataset comprising 357 patients was analyzed. Subsequently, prior treatment-naïve and relapser (223 patients) and nonresponder (134 patients) of interferon-based treatment subsets were analyzed to identify predictors of SVR. A subset of nonresponders (106 patients) who were treated ≥24 weeks was also analyzed to identify predictors for viral relapse.

Results: In the integrated dataset, prior treatment response was significantly associated with SVR. In subset analyses, interleukin-28B (IL28B) TT genotype and undetectable plasma HCV RNA level at week 4 were associated in treatment-naïve patients and relapsers [odds ratio (OR); 4.106 and 3.701, respectively]. In the nonresponders, the IL28B TT genotype population was very small, and inosine triphosphatase (ITPA) and undetectable plasma HCV RNA at week 4 were associated (OR; 2.506 and 3.333, respectively). Furthermore, ribavirin dose intensity (RBV-DI) and detectable plasma HCV RNA at week 4 were significantly associated with viral relapse (OR; 0.327 and 2.922, respectively).

Conclusion: IL28B and plasma HCV RNA level at week 4 were clinically relevant predictive factors for SVR in treatment-naïve patients and relapsers. Moreover, RBV-DI and plasma HCV level at week 4 were identified as relevant predictive factors for viral relapse in nonresponders.

Keywords: Hepatitis C; Predictive factor; Ribavirin dose intensity; Simeprevir; Viral relapse.

Publication types

  • Clinical Trial, Phase III

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacology
  • Drug Therapy, Combination
  • Female
  • Hepacivirus / drug effects*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology*
  • Humans
  • Interferons / administration & dosage*
  • Interleukins / genetics
  • Logistic Models
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Ribavirin / administration & dosage*
  • Simeprevir / administration & dosage*
  • Treatment Outcome
  • Viral Load / drug effects
  • Young Adult

Substances

  • Antiviral Agents
  • IFNL3 protein, human
  • Interleukins
  • RNA, Viral
  • Ribavirin
  • Interferons
  • Simeprevir