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

Stanislas Pol, Jeroen Aerssens, Stefan Zeuzem, Pietro Andreone, Eric J. Lawitz, Stuart Roberts, Zobair Younossi, Graham R. Foster, Roberto Focaccia, Andrzej Horban, Paul J. Pockros, Rolf P.G. Van Heeswijk, Sandra De Meyer, Don Luo, Martyn Botfield, Maria Beumont, Gaston Picchio

Research output: Contribution to journalArticle

52 Scopus citations

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 8 h) 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.

Original languageEnglish (US)
Pages (from-to)883-889
Number of pages7
JournalJournal of Hepatology
Volume58
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

Keywords

  • Direct-acting antiviral
  • Hepatitis C virus
  • REALIZE
  • Response predictors

ASJC Scopus subject areas

  • Hepatology

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