Gastroenterology

Gastroenterology

Volume 147, Issue 1, July 2014, Pages 132-142.e4
Gastroenterology

Original Research
Full Report: Clinical—Liver
Effectiveness of Telaprevir or Boceprevir in Treatment-Experienced Patients With HCV Genotype 1 Infection and Cirrhosis

https://doi.org/10.1053/j.gastro.2014.03.051Get rights and content

Background & Aims

We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis.

Methods

In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy and safety. This observational study did not allow for direct comparison of the 2 regimens.

Results

Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count greater than 100,000/mm3. Severe adverse events occurred in 49.9% of cases, including liver decompensation, severe infections in 10.4%, and death in 2.2%. In multivariate analysis, baseline serum albumin level less than 35 g/L and baseline platelet counts of 100,000/mm3 or less predicted severe side effects or death.

Conclusions

Relatively high percentages of real-life, treatment-experienced patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. ClinicalTrials.gov number: NCT01514890.

Section snippets

Patients

The ANRS CO20-CUPIC cohort is a national multicenter prospective cohort study conducted in 56 French centers (ClinicalTrials.gov number: NCT01514890). From February 2011 to April 2012, patients with compensated cirrhosis (Child–Pugh class A) chronically infected with HCV genotype 1 who failed a prior course of IFN with or without RBV and started triple combination therapy in the French Early Access Program in the participating centers were included. Initially, only relapsers (or patients with a

Baseline Demographics and Disease Characteristics

A total of 660 patients older than 18 years of age were enrolled in 56 centers; 511 patients reached week 60 of follow-up evaluation and thus were included in this analysis, including 299 treated with TVR and 212 treated with BOC. The baseline demographics and disease characteristics are shown in Table 1. Of the 511 patients, 346 (67.7%) were men, and their mean age was 57.0 ± 9.7 years. The prior treatment response was a relapse or a virologic breakthrough in 226 cases (44.3%, including 17

Discussion

The CUPIC cohort is a large cohort of treatment-experienced cirrhotic patients infected with HCV genotype 1 treated with BOC or TVR in combination with peg-IFN and RBV in the real-life setting. Because the choice of TVR or BOC was made by the treating physicians and the patients were not randomized, no comparison can be made between the 2 PIs. However, our results provide, for each drug regimen, an accurate reflection of what can be expected in terms of antiviral efficacy and safety in this

Acknowledgments

The authors thank David Marsh for writing assistance.

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    Authors names in bold designate shared co-first author.

    Conflicts of interest These authors disclose the following: Christophe Hézode has been a clinical investigator, speaker, and/or consultant for Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche; Hélène Fontaine has been a clinical investigator and/or speaker for Bristol-Myers Squibb, Janssen Pharmaceuticals, Merck Sharp and Dohme, Gilead Sciences, and Roche; Fabien Zoulim has been a speaker and/or consultant for Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche; Dominique Larrey has been a clinical investigator, speaker, and/or consultant for Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche; Valérie Canva has been a clinical investigator and/or speaker for Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche; Victor de Ledinghen has been a clinical investigator, speaker, and/or consultant for Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche; Thierry Poynard has been a clinical investigator, speaker, and/or consultant for Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, and Merck Sharp and Dohme; Didier Samuel has been a consultant for Astellas, Biotest, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Laboratoire Français du Fractionnement et des Biotechnologies, Merck Sharp and Dohme, Novartis, and Roche; Marc Bourlière has been a clinical investigator, speaker, and/or consultant for Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Glaxo Smith Kline, Janssen Pharmaceuticals, Merck Sharp and Dohme, Roche, and Vertex; Laurent Alric has been a clinical investigator, speaker, and/or consultant for Bristol-Myers Squibb, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche; Jean-Pierre Zarski has been a speaker and/or consultant for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, Roche, and Siemens; Patrick Marcellin has been a clinical investigator, speaker, and/or consultant for Abbvie, Alios BioPharm, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, Novartis, Pfizer, Roche, and Vertex Pharmaceuticals; Véronique Loustaud-Ratti has been a clinical investigator, speaker, and/or consultant for Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche, and has received grant/research support from Bristol-Myers Squibb and Roche; Olivier Chazouilleres has been a clinical investigator, speaker, and/or consultant for Aptalis, Echosens, Gilead Sciences, Mayoly-Spindler, and Roche; Armand Abergel has been a clinical investigator, speaker, and/or consultant for Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche; Dominique Guyader has been a clinical investigator, speaker, and/or consultant for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche; Albert Tran has been a clinical investigator for Janssen Pharmaceuticals and Merck Sharp and Dohme; Vincent Di Martino has been a clinical investigator, speaker, and/or consultant for Bristol-Myers Squibb, Gilead Sciences, Merck Sharp and Dohme, and Roche; Xavier Causse has been a consultant for Janssen Pharmaceuticals and Merck Sharp and Dohme; Thong Dao has been a consultant for Gilead Sciences and Merck Sharp and Dohme; Patrice Cacoub has received consulting and lecture fees from Bristol-Myers Squibb, Gilead, Roche, Merck Sharp, Servier, and Vifor; Jérome Gournay has been a speaker and/or consultant for Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche; Patrick Hillon has been a clinical investigator, speaker, and/or consultant for Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Roche; Pierre Attali has been a clinical investigator for Boehringer Ingelheim, Bristol-Myers Squibb, Cytheris, Gilead Sciences, and Novartis; Thierry Fontanges has been a speaker and/or consultant for Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, and Merck Sharp and Dohme; Isabelle Rosa has been a speaker and/or consultant for Janssen Pharmaceuticals and Merck Sharp and Dohme; Jean-Michel Pawlotsky has received research grants from Gilead Sciences, and has served as an advisor for Abbott, Abbvie, Achillion, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Idenix, Janssen, Janssen Therapeutics, Merck, Novartis, and Roche; Stanislas Pol has received consulting and lecture fees from Bristol-Myers Squibb, Boehringer Ingelheim, Tibotec, Vertex, Gilead, Roche, Schering-Plough/Merck, Novartis, Abbott/Abbvie, Sanofi, and Glaxo Smith Kline, and grants from Bristol-Myers Squibb, Gilead, Roche, and Merck/Schering Plough; and Jean-Pierre Bronowicki has been a clinical investigator, speaker, and/or consultant for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp and Dohme, Novartis, and Roche. The remaining authors disclose no conflicts.

    Funding Sponsored and funded by the National Agency for Research on AIDS and Viral Hepatitis and in part by the Association Française pour l'Etude du Foie.

    Additional Compassionate Use of Protease Inhibitors in Viral C Cirrhosis investigators are listed in the Supplementary.

    Authors share co-first authorship.

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