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

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

来源：Journal of Hepatology, 2013, 58(5): 883-889.

DOI：10.1016/j.jhep.2012.12.023

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

Background %26 Aims: Nucleotide polymorphisms upstream of the interleukin 28B (IL28B) gene are strongly associated with hepatitis C virus (HCV) clearance in treatment-nave patients treated with peginterferon/ribavirin (PegIFN/RBV). This sub-analysis 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. %26lt;br%26gt;Methods: Treatment-experienced patients were randomized to 12 weeks of telaprevir (750 mg every 8 h) with/without a 4-week PegIFN/RIN lead-in, or placebo, each with PegIFN-alpha-2a (180 mu g/week) and ribavirin (1000-1200 mg/day) for 48 weeks overall. Data from telaprevir arms were pooled. %26lt;br%26gt;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 %26gt;0.16 in pairwise comparison among CC, TT, and CT). Variations in rapid virologic response and relapse rates were noted in certain patient subgroups. %26lt;br%26gt;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.

• 出版日期2013-5