Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial


  • See Editorial on Page 1874

  • 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.


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)