Clinical and virological predictors of sustained response with an interferon-based simeprevir regimen for patients with chronic genotype 1 hepatitis C virus infection

New Microbiol. 2017 Jan;40(1):19-26. Epub 2017 Jan 9.

Abstract

Simeprevir plus peg-interferon/ribavirin (PR) is approved to treat chronic hepatitis C (HCV) genotype 1 (GT1) and GT4 infection. This study aimed to assess baseline and on-treatment the factors predictive of sustained virologic response 12-weeks post-treatment (SVR12) in patients receiving 12 weeks of simeprevir plus PR followed by 12 or 36 weeks of PR. Data from participants in four studies (QUEST-1, QUEST-2, ATTAIN and PROMISE) were pooled to examine the efficacy and safety of simeprevir+PR in HCV GT1 patients. The predictive power of baseline variables for SVR12 was assessed using univariate and multivariate logistic regression models while the relationship between early (Week 4) on-treatment response and SVR12 was analyzed by GT1 subtype and treatment experience. Data for 1160 patients were analyzed (overall SVR12: 71%). Baseline factors predictive of SVR12 were: IL28B CC genotype, GT1a/Q80K-negative, treatment-naïve/prior relapser, no cirrhosis, HCV-RNA ≤2,000,000IU/mL, albumin >42g/L, platelets >200x109 /L. Patients with HCV GT1b (86%), IL28B CC genotype (87%), and treatment-naïve patients (83%) were predicted to achieve the highest SVR12 rates and rates of rapid virologic response. Week 4 early on-treatment response identified treatment-naïve and prior relapse patients likely to achieve SVR12. Patients likely to respond to simeprevir+PR can be identified using baseline factors. Early on-treatment response predicts treatment success.

Keywords: Genotype 1; Hepatitis C; Interferon-based therapy; Simeprevir.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Albumins
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Interferons / administration & dosage
  • Interferons / therapeutic use*
  • Interleukins / genetics
  • Interleukins / metabolism
  • Male
  • Middle Aged
  • RNA, Viral
  • Recurrence
  • Ribavirin / administration & dosage
  • Ribavirin / therapeutic use*
  • Simeprevir / administration & dosage
  • Simeprevir / therapeutic use*
  • Young Adult

Substances

  • Albumins
  • interferon-lambda, human
  • Interleukins
  • RNA, Viral
  • Ribavirin
  • Interferons
  • Simeprevir