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

Abstract

UNLABELLED:

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.

• Authors: Zobair Younossi, Francesco Negro, Lawrence Serfaty, Stanislas Pol, Moises Diago, Stefan Zeuzem, Pietro Andreone, Eric J Lawitz, Stuart Roberts, Roberto Focaccia, Graham R Foster, Andrzej Horban, Isabelle Lonjon-Domanec, Bruce Coate, Ralph DeMasi, Gaston Picchio, James Witek
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 58 Issue 6 Pg. 1897-906 (Dec 2013) ISSN: 1527-3350 [Electronic] United States
• PMID: 24382638 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 by the American Association for the Study of Liver Diseases.

Chemical References

• Interferon alpha-2
• Interferon-alpha
• Oligopeptides
• RNA, Viral
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• telaprevir
• peginterferon alfa-2b

Topics

• Adult
• Aged
• Female
• Hepatitis C, Chronic (drug therapy)
• Homeostasis (genetics)
• Humans
• Insulin Resistance (physiology)
• Interferon alpha-2
• Interferon-alpha (administration & dosage)
• Male
• Middle Aged
• Models, Biological
• Oligopeptides (therapeutic use)
• Polyethylene Glycols (administration & dosage)
• RNA, Viral (blood)
• Recombinant Proteins (administration & dosage)
• Regression Analysis
• Ribavirin (administration & dosage)
• Treatment Failure
• Treatment Outcome