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

被引：52

作者：

Pol, Stanislas ^{[1
,2
]}

Aerssens, Jeroen ^{[3
]}

Zeuzem, Stefan ^{[4
]}

Andreone, Pietro ^{[5
]}

Lawitz, Eric J. ^{[6
]}

Roberts, Stuart ^{[7
]}

Younossi, Zobair ^{[8
,9
]}

Foster, Graham R. ^{[10
]}

Focaccia, Roberto ^{[11
]}

Horban, Andrzej ^{[12
]}

Pockros, Paul J. ^{[13
,14
]}

Van Heeswijk, Rolf P. G. ^{[3
]}

De Meyer, Sandra ^{[3
]}

Luo, Don ^{[15
]}

Botfield, Martyn ^{[16
]}

Beumont, Maria ^{[3
]}

Picchio, Gaston ^{[15
]}

机构：

[1] Univ Paris 05, INSERM, U1016, Paris, France

[2] Hop Cochin, Assistance Publ Hop Paris, F-75014 Paris, France

[3] Janssen Infect Dis BVBA, Beerse, Belgium

[4] Goethe Univ Frankfurt, Med Ctr, D-60054 Frankfurt, Germany

[5] Univ Bologna, Bologna, Italy

[6] Alamo Med Res, San Antonio, TX USA

[7] Alfred Hosp, Dept Gastroenterol, Melbourne, Vic, Australia

[8] Inova Fairfax Hosp, Ctr Liver Dis, Falls Church, VA USA

[9] Inova Fairfax Hosp, Dept Med, Falls Church, VA USA

[10] Univ London, Inst Cell & Mol Sci, London, England

[11] Emilio Ribas Infect Dis Inst, Sao Paulo, Brazil

[12] Med Univ Warsaw, Warsaw, Poland

[13] Scripps Clin, La Jolla, CA USA

[14] Scripps Translat Sci Inst, La Jolla, CA USA

[15] Janssen Res & Dev, Titusville, NJ USA

[16] Vertex Pharmaceut Inc, Cambridge, MA USA

来源：

JOURNAL OF HEPATOLOGY | 2013年 / 58卷 / 05期

关键词：

Direct-acting antiviral; Hepatitis C virus; REALIZE; Response redictors; HEPATITIS-C VIRUS; COMBINATION TREATMENT; SPONTANEOUS CLEARANCE; VIROLOGICAL RESPONSE; GENETIC-VARIATION; POLYMORPHISM; BOCEPREVIR; RIBAVIRIN; ASSOCIATION; ALPHA-2A;

D O I：

10.1016/j.jhep.2012.12.023

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & 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. 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. 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. (c) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：883 / 889

页数：7