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.

Limited impact of IL28B genotype on response rates in telaprevir-treated patients with prior treatment failure / Pol, S; Aerssens, J; Zeuzem, S; Andreone, P; Lawitz, Ej; Roberts, S; Younossi, Z; Foster, Gr; Focaccia, R; Horban, A; Pockros, Pj; Van Heeswijk, Rp; De Meyer, S; Luo, D; Botfield, M; Beumont, M; Picchio, G.. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - 58:5(2013), pp. 883-889. [10.1016/j.jhep.2012.12.023]

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

Andreone P;
2013

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.
2013
58
5
883
889
Limited impact of IL28B genotype on response rates in telaprevir-treated patients with prior treatment failure / Pol, S; Aerssens, J; Zeuzem, S; Andreone, P; Lawitz, Ej; Roberts, S; Younossi, Z; Foster, Gr; Focaccia, R; Horban, A; Pockros, Pj; Van Heeswijk, Rp; De Meyer, S; Luo, D; Botfield, M; Beumont, M; Picchio, G.. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - 58:5(2013), pp. 883-889. [10.1016/j.jhep.2012.12.023]
Pol, S; Aerssens, J; Zeuzem, S; Andreone, P; Lawitz, Ej; Roberts, S; Younossi, Z; Foster, Gr; Focaccia, R; Horban, A; Pockros, Pj; Van Heeswijk, Rp; De Meyer, S; Luo, D; Botfield, M; Beumont, M; Picchio, G.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1237278
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