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Insulin resistance and response to telaprevir plus peginterferon α and ribavirin in treatment-naïve patients infected with HCV genotype 1
  1. Lawrence Serfaty1,
  2. Xavier Forns2,
  3. Tobias Goeser3,
  4. Peter Ferenci4,
  5. Frederik Nevens5,
  6. Giampiero Carosi6,
  7. Joost P Drenth7,
  8. Isabelle Lonjon-Domanec8,
  9. Ralph DeMasi9,
  10. Gaston Picchio9,
  11. Maria Beumont10,
  12. Patrick Marcellin11
  1. 1Service d'Hépatologie and INSERM UMRS 938, Hôpital Saint Antoine, Université Pierre&Marie Curie, Paris, France
  2. 2Liver Unit, Hospital Clinic, IDIBAPS, Ciberehd, University of Barcelona, Barcelona, Spain
  3. 3Klinikum der Universität zu Köln, Köln, Germany
  4. 4Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria
  5. 5Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium
  6. 6Clinic of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy
  7. 7Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  8. 8Janssen Pharmaceuticals, Paris, France
  9. 9Tibotec Inc, Titusville, New Jersey, USA
  10. 10Tibotec BVBA, Beerse, Belgium
  11. 11Service d'Hépatologie and INSERM CRB3, Hôpital Beaujon, APHP, Université Paris-Diderot, Clichy, France
  1. Correspondence to Dr Lawrence Serfaty, Hôpital St Antoine, 184 Rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France; lawrence.serfaty{at}sat.aphp.fr

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.

Design 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).

Conclusion 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.

  • Vx-950
  • homeostatis model assessment
  • LDL-cholesterol
  • fibrosis
  • direct-acting antiviral agent
  • hepatitis C
  • liver transplantation
  • chronic hepatitis
  • chronic liver disease
  • hepatic encephalopathy
  • Wilson's disease
  • haemochromatosis
  • haemodynamics in cirrhosis
  • hepatocellular carcinoma
  • hepatitis B
  • hepatic haemodynamics
  • portal hypertension
  • cirrhosis
  • liver failure
  • liver transplantation
  • chronic viral hepatitis
  • autoimmune hepatitis
  • hepatitis D
  • cirrhosis

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Footnotes

  • Funding This clinical trial was sponsored by Tibotec BVBA and Vertex Pharmaceuticals Inc. The authors received general editing/styling and coordination support from Gardiner-Caldwell Communications, which was funded by Janssen Pharmaceuticals.

  • Competing interests LS: consulting, advisory committees or review panels (Schering-Plough, Tibotec, Merck Sharp & Dohme, Roche, Bristol-Meyers Squibb (BMS), Gilead, GlaxoSmithKline (GSK) and Axcan Pharma); grant/research support (Roche and Schering-Plough); speaking and teaching (Roche, Schering-Plough, Gilead, BMS, Tibotec and Axcan Pharma). XF: advisory committees or review panels (Schering-Plough, Tibotec, and Merck Sharp & Dohme); grant/research support (Schering-Plough). TG: speaking and teaching (Roche, Essex, BMS, Gilead, Novartis and Falk); advisory committees or review panels (BMS); grant/research support (Roche). PF: speaking and teaching (Roche, Gilead, and Salix); advisory committees or review panels (Roche, Salix, Madaus Rottapharm, Tibotec, Novartis, Vertex and Boehringer Ingelheim); grant/research support (Roche and Madaus Rottapharm); patent held/filed (Madaus Rottapharm). FN: consulting (Ipsen, Gilead, BMS, CAF-DCF, Hepa Wash and Gambro); grant/research support (Roche, Merck Sharp & Dohme and Novartis). GC: advisory and committees or review panels (Janssen Cilag); speaking and teaching (Schering Plough, Roche and BMS). JD: declares no conflict of interest. PM: grant support (Roche, Schering-Plough and Gilead); investigator (Roche, Schering-Plough, Gilead, BMS, Vertex, Novartis, Tibotec, Merck Sharp & Dohme, Boehringer Ingelheim, Biolex and Intermune); speaker and/or expert (Roche, Schering-Plough, Gilead, BMS, Vertex, Novartis, Pharmasset, Tibotec, Merck Sharp & Dohme, Biolex, Intermune and Zymogenetics). IL-D, RDeM, GP and MB: employment (Janssen Pharmaceuticals/Tibotec/Johnson and Johnson).

  • Patient consent Obtained.

  • Ethics approval The study protocol was reviewed and approved by the appropriate institutional ethics committees/health authorities.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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