TY - JOUR
T1 - Limited impact of IL28B genotype on response rates in telaprevir-treated patients with prior treatment failure
AU - Pol, Stanislas
AU - Aerssens, Jeroen
AU - Zeuzem, Stefan
AU - Andreone, Pietro
AU - Lawitz, Eric J.
AU - Roberts, Stuart
AU - Younossi, Zobair
AU - Foster, Graham R.
AU - Focaccia, Roberto
AU - Horban, Andrzej
AU - Pockros, Paul J.
AU - Van Heeswijk, Rolf P.G.
AU - De Meyer, Sandra
AU - Luo, Don
AU - Botfield, Martyn
AU - Beumont, Maria
AU - Picchio, Gaston
PY - 2013/5
Y1 - 2013/5
N2 - 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.
AB - 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.
KW - Direct-acting antiviral
KW - Hepatitis C virus
KW - REALIZE
KW - Response predictors
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UR - http://www.scopus.com/inward/citedby.url?scp=84876294731&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2012.12.023
DO - 10.1016/j.jhep.2012.12.023
M3 - Article
C2 - 23321318
AN - SCOPUS:84876294731
VL - 58
SP - 883
EP - 889
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 5
ER -