title: Limited impact of IL28B genotype on response rates in telaprevir-treated patients with prior treatment failure.
abstract: OBJECTIVE
  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.
authors: Université Paris Descartes, INSERM Unité 1016, and Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris, France. stanislas.pol@cch.aphp.fr
authors: Stanislas
authors: S
authors: Pol
authors: Jeroen
authors: J
authors: Aerssens
authors: Stefan
authors: S
authors: Zeuzem
authors: Pietro
authors: P
authors: Andreone
authors: Eric J
authors: EJ
authors: Lawitz
authors: Stuart
authors: S
authors: Roberts
authors: Zobair
authors: Z
authors: Younossi
authors: Graham R
authors: GR
authors: Foster
authors: Roberto
authors: R
authors: Focaccia
authors: Andrzej
authors: A
authors: Horban
authors: Paul J
authors: PJ
authors: Pockros
authors: Rolf P G
authors: RP
authors: Van Heeswijk
authors: Sandra
authors: S
authors: De Meyer
authors: Don
authors: D
authors: Luo
authors: Martyn
authors: M
authors: Botfield
authors: Maria
authors: M
authors: Beumont
authors: Gaston
authors: G
authors: Picchio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C486464:telaprevir; C100416:peginterferon alfa-2a