Limited impact of IL28B genotype on response rates in telaprevir-treated patients with prior treatment failure

J Hepatol. 2013 May;58(5):883-9. doi: 10.1016/j.jhep.2012.12.023. Epub 2013 Jan 12.

Abstract

Background & aims: Nucleotide polymorphisms upstream of the interleukin 28B (IL28B) gene are strongly associated with hepatitis C virus (HCV) clearance in treatment-naïve patients treated with peginterferon/ribavirin (PegIFN/RBV). This subanalysis of the REALIZE study evaluated the impact of IL28B polymorphisms on sustained virologic response (SVR) in telaprevir-treated, HCV genotype 1-infected patients with prior PegIFN/RBV treatment failure.

Methods: Treatment-experienced patients were randomized to 12 weeks of telaprevir (750 mg every 8h) with/without a 4-week PegIFN/RBV lead-in, or placebo, each with PegIFN-α-2a (180 μg/week) and ribavirin (1000-1200 mg/day) for 48 weeks overall. Data from telaprevir arms were pooled.

Results: Eighty percent (527/662) of patients consented to genetic testing and were included. Similar proportions of patients had IL28B CC, CT and TT genotypes across treatment arms; baseline characteristics were generally well balanced. SVR rates were higher in the pooled telaprevir versus placebo group for all IL28B genotypes; CC: 79% versus 29%, respectively; CT: 60% versus 16%, respectively; TT: 61% versus 13%, respectively. Within each prior response category (relapse, partial or null response), SVR and viral breakthrough rates with telaprevir-based treatment were comparable across IL28B genotypes. IL28B genotype did not significantly affect SVR (2-step multivariate analyses; p >0.16 in pairwise comparison among CC, TT, and CT). Variations in rapid virologic response and relapse rates were noted in certain patient subgroups.

Conclusions: Our findings suggest that IL28B genotype has a limited impact on SVR rates with telaprevir-based therapy in treatment-experienced patients. IL28B genotyping may have limited utility in the baseline evaluation of similar patients considered for telaprevir-based therapy.

Trial registration: ClinicalTrials.gov NCT00703118.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Genotype*
  • Hepatitis C / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Oligopeptides / therapeutic use*
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Genetic / genetics
  • Protease Inhibitors / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Ribavirin / therapeutic use
  • Treatment Failure
  • Treatment Outcome
  • Young Adult

Substances

  • IFNL3 protein, human
  • Interferon-alpha
  • Interleukins
  • Oligopeptides
  • Protease Inhibitors
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • telaprevir
  • Interferons
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT00703118