title: Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial.
abstract: 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).
  
  
  CONCLUSIONS
  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.affiliation: Center for Liver Diseases and Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA.
authors.forename: Zobair
authors.initials: Z
authors.lastname: Younossi
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: Moises
authors.initials: M
authors.lastname: Diago
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lawitz
authors.forename: Stuart
authors.initials: S
authors.lastname: Roberts
authors.forename: Roberto
authors.initials: R
authors.lastname: Focaccia
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Andrzej
authors.initials: A
authors.lastname: Horban
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lonjon-Domanec
authors.forename: Bruce
authors.initials: B
authors.lastname: Coate
authors.forename: Ralph
authors.initials: R
authors.lastname: DeMasi
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
authors.forename: James
authors.initials: J
authors.lastname: Witek
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D012044:Regression Analysis; D012254:Ribavirin / Q000008:administration & dosage; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C417083:peginterferon alfa-2b