See Editorial on Page 1874
Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial
Article first published online: 17 OCT 2013
© 2013 by the American Association for the Study of Liver Diseases
Volume 58, Issue 6, pages 1897–1906, December 2013
How to Cite
Younossi, Z., Negro, F., Serfaty, L., Pol, S., Diago, M., Zeuzem, S., Andreone, P., Lawitz, E. J., Roberts, S., Focaccia, R., Foster, G. R., Horban, A., Lonjon-Domanec, I., Coate, B., DeMasi, R., Picchio, G. and Witek, J. (2013), Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial. Hepatology, 58: 1897–1906. doi: 10.1002/hep.26437
Potential conflict of interest: Zobair Younossi: Consultant or Advisory Board member for Vertex, Gilead, Salix, Janssen, Coneatus and Enterome. Francesco Negro: Consultant for MSD, Roche, Gilead and Janssen; Research grants from Roche and Novartis. Lawrence Serfaty: Consultant for Abbott, Aptalis, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Genfit, Janssen, MSD/Schering-Plough, Pfizer, Roche, Vertex. Stanislas Pol: Consultant for Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Vertex, Gilead, Roche, Schering-Plough/Merck, Novartis, Abbott, Sanofi and GlaxoSmithKline; Research grants from Bristol-Myers Squibb, Gilead, Roche and Merck/Schering Plough. Moises Diago: Consultant for MSD, Janssen, Roche and Abbott. Stefan Zeuzem: Consultant for Abbott, Achillion, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Novartis, Presidio, Roche, Santaris and Vertex. Pietro Andreone: Advisory board member for Roche, MSD, Janssen-Cilag; Consultant for MSD, Bristol-Myers Squibb; Research grants from Roche, MSD and Gilead. Eric J Lawitz: Research grants from Abbott, Achillion, Anadys, Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, GlobeImmune, Idenix, Idera, Inhibitex, Intercept, Janssen, Medarex, Medtronic, Merck & Co., Novartis, Pharmasset, Presidio, Roche, Schering-Plough, Santaris, Scynexis, Vertex, ViroChem and ZymoGenetics; Advisory board member for Abbott, Achillion, Anadys, Biolex, BioCryst, Biotica, Enanta, Gilead, GlobeImmune, Idenix, Inhibitex, Janssen, Merck & Co., Novartis, Pharmasset, Santaris, Tibotec, Theravance and Vertex; Speakers' Bureau member for Gilead, Kadmon, Merck & Co. and Vertex. Stuart Roberts: Advisory board member for Janssen and Roche. Roberto Focaccia: Research grants from Janssen, MSD, and Roche. Graham R. Foster: Consultant, Advisory Board member, and/or Speakers' Bureau member for Abbott, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Novartis, Presidio, Roche and Vertex. Andrzej Horban: Declares no competing interests. Isabelle Lonjon-Domanec, Bruce Coate, Ralph DeMasi, Gaston Picchio, and James Witek are employees of Janssen Research & Development, LLC. Dr. DeMasi owns stock in Janssen. Dr. Picchio and Dr. Witek own stock in Johnson & Johnson.
Clinical Trial Identifier: NCT00703118.
The REALIZE trial was funded by Janssen Pharmaceuticals and Vertex Pharmaceuticals.
- Issue published online: 26 NOV 2013
- Article first published online: 17 OCT 2013
- Accepted manuscript online: 4 APR 2013 05:04AM EST
- Manuscript Accepted: 31 MAR 2013
- Manuscript Received: 29 NOV 2012
Baseline homeostasis model assessment-estimated insulin resistance (HOMA-IR), a marker for insulin resistance, has been associated with poor virologic response to peginterferon alpha/ribavirin (PR) in chronic hepatitis C. We evaluated the association between baseline HOMA-IR and pretreatment factors on sustained virologic response (SVR) to telaprevir (TVR) in genotype 1 patients with hepatitis C and prior peginterferon/ribavirin (PR) treatment failure. Patients were randomized to 12 weeks of TVR (750 mg q8h) plus peginterferon (180 μg/week) and ribavirin (1,000-1,200 mg/day) (with or without a 4-week lead-in) followed by PR, or PR alone (PR48), for 48 weeks. Univariate and multiple logistic regression analyses explored the prognostic significance of baseline HOMA-IR alone and adjusted for other pretreatment factors and SVR. The TVR arms were pooled for the purposes of this analysis. In all, 662 patients were randomized; 578 had baseline HOMA-IR and other prognostic data and were included in this analysis. Median baseline HOMA-IR was 2.6 (interquartile range [IQR] 1.7-4.3); 207 (36%), 206 (36%), and 165 (29%) patients had baseline HOMA-IR <2, 2 to <4, and ≥4, respectively. Male gender, higher body mass index, triglycerides, gamma-glutamyl transpeptidase, maximum alanine aminotransferase/aspartate aminotransferase, and fibrosis stage were associated with higher baseline HOMA-IR. Baseline HOMA-IR was associated with SVR in univariate analysis, but not after adjustment for other baseline prognostic factors (TVR: OR = 0.95, 95% confidence interval [CI]: 0.71,1.29; PR48: 0.60; 95% CI: 0.25,1.43). Conclusion: In patients with prior PR treatment failure, baseline HOMA-IR correlated with SVR in univariate but not multivariate analyses, suggesting other factors have a more direct causal relationship with virologic response to TVR-based therapy than HOMA-IR. (Hepatology 2013; 58:1897–1906)