title: Insulin resistance and response to telaprevir plus peginterferon α and ribavirin in treatment-naive patients infected with HCV genotype 1.
abstract: OBJECTIVE
  Insulin resistance is a predictor of poor response to peginterferon/ribavirin in patients infected with the chronic hepatitis C virus (HCV). There are no data on direct-acting antivirals. This exploratory analysis assessed the effect of metabolic factors and insulin resistance, measured by homoeostatic model assessment (HOMA), on virological response to telaprevir in Study C208.
  
  
  METHODS
  Overall, 161 HCV genotype 1-infected, treatment-naïve patients received 12 weeks of telaprevir plus peginterferon/ribavirin, then 12/36 weeks of peginterferon/ribavirin depending on on-treatment response criteria. The prognostic significance of several factors, including HOMA-insulin resistance (HOMA-IR), on virological response at weeks 4 and 12, end of treatment and 24 weeks after treatment was explored by multiple regression analysis.
  
  
  RESULTS
  Baseline HOMA-IR data were available for 147 patients; baseline characteristics were consistent with the overall population. Baseline HOMA-IR <2, 2-4 and >4 was seen in 54%, 30% and 16% of patients, respectively. Neither response rates (any time point) nor week 4 viral load decline were significantly influenced by baseline HOMA-IR. In multivariate analyses, fibrosis stage and low-density lipoprotein cholesterol level were predictive of sustained virological response (OR 0.47 and 1.02, respectively). After the end of treatment, HOMA-IR was significantly lower in patients with sustained virological response than in those without (0.61 vs 1.34 for relapsers and 1.15 for non-responders; p<0.05).
  
  
  CONCLUSIONS
  In this study, baseline HOMA-IR was not predictive of virological response to telaprevir in HCV genotype 1-infected, treatment-naïve patients, while sustained virological response was associated with improved HOMA-IR. These results suggest that metabolic factors and insulin resistance do not have a significant effect on telaprevir-based treatment efficacy.
authors.affiliation: Service d'Hépatologie and INSERM UMRS 938, Hôpital Saint Antoine, Université Pierre&Marie Curie, Paris, France. lawrence.serfaty@sat.aphp.fr
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.forename: Tobias
authors.initials: T
authors.lastname: Goeser
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Frederik
authors.initials: F
authors.lastname: Nevens
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
authors.forename: Joost P
authors.initials: JP
authors.lastname: Drenth
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lonjon-Domanec
authors.forename: Ralph
authors.initials: R
authors.lastname: DeMasi
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
authors.forename: Maria
authors.initials: M
authors.lastname: Beumont
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D007333:Insulin Resistance; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a