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
N1 - Funding Information:
The clinical trial was sponsored by Janssen Pharmaceuticals and Vertex Pharmaceuticals. Medical writing and editing support, and assistance in collating author contributions, was provided by Joanne Williams (Medical Writer, Gardiner-Caldwell Communications, Macclesfield, UK), the funding for which was provided by Janssen Pharmaceuticals.
Funding Information:
S. Pol has received consulting and lecturing fees from Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Vertex, Gilead, Roche, Schering-Plough/Merck, Novartis, Abbott, Sanofi and GlaxoSmithKline, and grants from Bristol-Myers Squibb, Gilead, Roche and Merck/Schering Plough. S. Zeuzem has received consulting and lecture fees and/or been a member of Advisory Boards for Abbott, Achillion, Anadys Pharmaceuticals, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, iTherx, Merck, Novartis, Pharmasset, Santaris, Roche, Janssen and Vertex Pharmaceuticals, and has been on Speakers’ bureau for Bristol-Myers Squibb, Gilead, Merck, Novartis and Roche. P. Andreone has been a consultant for Roche, Janssen, Gilead and Schering-Plough/Merck, received grant/research support from Roche and Gilead, been principal investigator in clinical trials for Roche, Novartis, Bristol-Myers Squibb, Gilead, GlaxoSmithKline and Janssen. E.J. Lawitz has received research/grant support from Abbott Laboratories, Anadys Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex, Medarex, Medtronic, Novartis, Pharmasset, Roche, Schering-Plough/Merck, Janssen, Valeant Pharmaceuticals International, Vertex Pharmaceuticals, ViroChem Pharma and ZymoGenetics. S. Roberts has been a member of a Global Advisory Board for Roche, and investigator in clinical trials for Roche, Janssen, Gilead, Bristol-Myers Squibb, GlaxoSmithKline, Boehringer Ingelheim and Merck. Z. Younossi has been a consultant or member of Advisory Boards for Vertex, Janssen and GlaxoSmithKline. G.R. Foster has received research funding and consulting/lecture fees from Roche, Chughai, Janssen, GlaxoSmithKline, Novartis, Gilead, Merck and Abbott. R. Focaccia has received research sponsorship from Roche, Schering-Plough/Merck, Janssen, Bristol-Myers Squibb, and GlaxoSmithKline. A. Horban has no conflicts of interest to disclose. P.J. Pockros has received consulting fees from Genentech/Roche, Vertex, Merck, Gilead, Bristol-Myers Squibb, Abbott, Janssen, Pfizer, Conatus, Novartis, Achillion, and Regulus, and research support/grants from Genentech/Roche, Vertex, Gilead, Bristol-Myers Squibb, Abbott, Quest, Conatus, Janssen, Pfizer, Globeimmune, Debio, Novartis, Mochida, Zymogenetics, and Human Genome Sciences. J. Aerssens, R. Van Heeswijk, S. De Meyer and M. Beumont are full-time employees of Janssen Infectious Diseases BVBA. D. Luo and G. Picchio are full-time employees of Janssen Research and Development. M. Botfield is a full-time employee of Vertex Pharmaceuticals Incorporated.
Funding Information:
The authors thank the study coordinators, nurses, and patients involved in the trial. The REALIZE trial was funded by Janssen Pharmaceuticals and Vertex Pharmaceuticals . The authors also acknowledge Isabelle Lonjon-Domanec for her contributions, and Joanne Williams (Medical Writer, Gardiner-Caldwell Communications, Macclesfield, UK) for medical writing, editing, and coordination support, which was funded by Janssen Pharmaceuticals .
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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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 -