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

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• 作者：Stanislas Pol¹ ; ^{stanislas.pol@cch.aphp.fr} ; Jeroen Aerssens² ; Stefan Zeuzem³ ; Pietro Andreone⁴ ; Eric J. Lawitz⁵ ; Stuart Roberts⁶ ; Zobair Younossi⁷ ; Graham R. Foster⁸ ; Roberto Focaccia⁹ ; Andrzej Horban¹⁰ ; Paul J. Pockros¹¹ ; Rolf P.G. Van Heeswijk² ; Sandra De Meyer² ; Don Luo¹² ; Martyn Botfield¹³ ; Maria Beumont² ; Gaston Picchio¹²
• 关键词：DAA ; direct-acting antiviral ; HBV ; hepatitis B virus ; HCV ; hepatitis C virus ; HIV ; human immunodeficiency virus ; LLOD ; lower limit of detection ; LLOQ ; lower limit of quantification ; NS3 ; non-structural protein 3 ; OR ; odds ratio ; PCR ; polymerase chain reac
• 刊名：Journal of Hepatology
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：58
• 期：5
• 页码：883-889
• 全文大小：716 K

文摘

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Background & Aims

Nucleotide polymorphisms upstream of the interleukin 28B (IL28B) gene are strongly associated with hepatitis C virus (HCV) clearance in treatment-na?ve 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-¦Á-2a (180 ¦Ìg/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.